To see the other types of publications on this topic, follow the link: Xenobiotik.
Journal articles on the topic 'Xenobiotik'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Xenobiotik.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Hertz, R., and J. Bar−Tana. "The acylation of proteins by xenobiotic amphipathic carboxylic acids in cultured rat hepatocytes." Biochemical Journal 254, no. 1 (August 15, 1988): 39–44. http://dx.doi.org/10.1042/bj2540039.
Full textAbstract:
Three xenobiotic amphipathic carboxylates, namely MEDICA 16, nafenopin and bezafibrate, which differ remarkably in their hydrophobic backbones, were found to acylate membrane and cytosolic liver proteins in cultured rat hepatocytes. The acylation patterns observed were time- and dose-dependent, and the acylated residue consisted of the original xenobiotic. The acylation patterns generated by the three xenobiotic carboxylates included common proteins which were acylated by the three xenobiotics (e.g. proteins of 32, 52, 56 and 72 kDa) as well as unique proteins which were specifically acylated by the respective xenobiotics. The acylation of liver proteins by either MEDICA 16 or nafenopin remained unaffected under conditions where protein synthesis was completely inhibited by cycloheximide. Protein acylation thus offers a common mode of action of xenobiotic amphipathic carboxylates, which may, however, result in diverse xenobiotyl-protein adducts. The xenobiotyl-acylated proteins might be involved in triggering some of the biological effects exerted by xenobiotic amphipathic carboxylates employed as hypolipidaemic effectors, peroxisomal proliferators or preadipocyte convertors.
2
Musolff, A., S. Leschik, M. T. Schafmeister, F. Reinstorf, G. Strauch, R. Krieg, and M. Schirmer. "Evaluation of xenobiotic impact on urban receiving waters by means of statistical methods." Water Science and Technology 62, no. 3 (August 1, 2010): 684–92. http://dx.doi.org/10.2166/wst.2010.930.
Full textAbstract:
Xenobiotics in urban receiving waters are an emerging problem. A sound knowledge of xenobiotic input, distribution and fate in the aquatic environment is a prerequisite for risk assessments. Methods to assess the impact of xenobiotics on urban receiving waters should address the diverse characteristics of the target compounds and the spatiotemporal variability of concentrations. Here, we present results from a one-year-monitoring program concerning concentrations of pharmaceuticals, additives from personal care products and industrial chemicals in an urban drainage catchment in untreated and treated wastewater, surface water and groundwater. Univariate and multivariate statistical methods were applied to characterize the xenobiotic concentrations. Correlation and principal component analysis revealed a pronounced pattern of xenobiotics in the surface water samples. The concentrations of several xenobiotics were characterized by a negative proportionality to the water temperature. Therefore, seasonal attenuation is assumed to be a major process influencing the measured concentrations. Moreover, dilution of xenobiotics the surface water was found to significantly influence the concentrations. These two processes control more the xenobiotic occurrence in the surface water than the less pronounced concentration pattern in the wastewater sources. For the groundwater samples, we assume that foremost attenuation processes lead to the found differentiation of xenobiotics.
3
Adrir, Mutia Syarifah, Ratna Stia Dewi, and Ajeng Arum Sari. "Aktivitas Enzimatik Isolat Trametes spp. dari Kebun Raya Baturraden dalam Pewarna Batik dengan Variasi Konsentrasi Indigosol Blue Glukosa." BioEksakta : Jurnal Ilmiah Biologi Unsoed 2, no. 2 (July 25, 2020): 174. http://dx.doi.org/10.20884/1.bioe.2020.2.2.1810.
Full textAbstract:
Indigosol Blue merupakan salah satu zat warna sintetik Antraquinon yang digunakan sebagai pewarna biru pada industri pencelupan tekstil dan bersifat rekalsitran dan non-biodegradable, sehingga tidak mudah rusak oleh perlakuan kimia maupun fotolitik. Isolat Trametes sp. diyakini memiliki kemampuan mentransformasi komponen pewarna melalui mekanisme degradasi enzimatik. Trametes sp. mampu menghasilkan enzim ekstraseluler ligninolitik yang dapat mendegradasi komponen xenobiotik dalam limbah pewarna indigosol menjadi bentuk yang tidak toksik di lingkungan. Penelitian bertujuan untuk mengetahui kemampuan tiga isolat uji dalam menghasilkan enzim dalam pewarna Indigosol Blue pada konsentrasi glukosa berbeda serta mengetahui isolat dengan konsentrasi glukosa optimum yang memiliki aktivitas enzim terbaik dalam pewarna Indigosol Blue. Pengukuran aktivitas enzimatik dilakukan dengan metode spektrofotometri. Hasil penelitian menunjukkan bahwa isolat-isolat uji dapat menghasilkan enzim dalam pewarna Indigosol Blue pada konsentrasi glukosa berbeda. Aktivitas enzim pada masing-masing perlakuan berbeda-beda dan menunjukkan hasil yang signifikan. Data uji lanjut memperlihatkan bahwa isolat Trametes sp. strain A memiliki aktivitas enzim terbaik dalam pewarna Indigosol Blue dengan konsentrasi glukosa 0,5%. Penelitian juga menunjukkan bahwa konsentrasi glukosa di atas 0.5% dapat menghambat aktivitas lakase, sehingga aktivitas lakase dalam zat pewarna rendah.
Kata kunci: enzim ligninolitik, fungi, glukosa, Indigosol Blue, Trametes sp.
4
Sugrue, Elena, Carol J. Hartley, Colin Scott, and Colin J. Jackson. "The Evolution of New Catalytic Mechanisms for Xenobiotic Hydrolysis in Bacterial Metalloenzymes." Australian Journal of Chemistry 69, no. 12 (2016): 1383. http://dx.doi.org/10.1071/ch16426.
Full textAbstract:
An increasing number of bacterial metalloenzymes have been shown to catalyse the breakdown of xenobiotics in the environment, while others exhibit a variety of promiscuous xenobiotic-degrading activities. Several different evolutionary processes have allowed these enzymes to gain or enhance xenobiotic-degrading activity. In this review, we have surveyed the range of xenobiotic-degrading metalloenzymes, and discuss the molecular and catalytic basis for the development of new activities. We also highlight how our increased understanding of the natural evolution of xenobiotic-degrading metalloenzymes can be been applied to laboratory enzyme design.
5
Afschar, Sonita, Janne M. Toivonen, Julia Marianne Hoffmann, Luke Stephen Tain, Daniela Wieser, Andrew John Finlayson, Yasmine Driege, et al. "Nuclear hormone receptor DHR96 mediates the resistance to xenobiotics but not the increased lifespan of insulin-mutant Drosophila." Proceedings of the National Academy of Sciences 113, no. 5 (January 19, 2016): 1321–26. http://dx.doi.org/10.1073/pnas.1515137113.
Full textAbstract:
Lifespan of laboratory animals can be increased by genetic, pharmacological, and dietary interventions. Increased expression of genes involved in xenobiotic metabolism, together with resistance to xenobiotics, are frequent correlates of lifespan extension in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila, and mice. The Green Theory of Aging suggests that this association is causal, with the ability of cells to rid themselves of lipophilic toxins limiting normal lifespan. To test this idea, we experimentally increased resistance of Drosophila to the xenobiotic dichlordiphenyltrichlorethan (DDT), by artificial selection or by transgenic expression of a gene encoding a cytochrome P450. Although both interventions increased DDT resistance, neither increased lifespan. Furthermore, dietary restriction increased lifespan without increasing xenobiotic resistance, confirming that the two traits can be uncoupled. Reduced activity of the insulin/Igf signaling (IIS) pathway increases resistance to xenobiotics and extends lifespan in Drosophila, and can also increase longevity in C. elegans, mice, and possibly humans. We identified a nuclear hormone receptor, DHR96, as an essential mediator of the increased xenobiotic resistance of IIS mutant flies. However, the IIS mutants remained long-lived in the absence of DHR96 and the xenobiotic resistance that it conferred. Thus, in Drosophila IIS mutants, increased xenobiotic resistance and enhanced longevity are not causally connected. The frequent co-occurrence of the two traits may instead have evolved because, in nature, lowered IIS can signal the presence of pathogens. It will be important to determine whether enhanced xenobiotic metabolism is also a correlated, rather than a causal, trait in long-lived mice.
6
Šíma, Martin, I. Netíková, and O. Slanař. "Pregnane Xenobiotic Receptors and Their Effect on Drug Elimination from the Organism." Prague Medical Report 114, no. 4 (2013): 205–13. http://dx.doi.org/10.14712/23362936.2014.9.
Full textAbstract:
Nuclear receptors are intracellular proteins which, having been activated by their more or less specific ligands, regulate (usually increase) the transcription of target genes. They thus participate in a regulation of a number of physiologic functions. Some of them – especially pregnane xenobiotic receptors – serve primarily as protection of the organism from the xenobiotic intoxication. This is because many xenobiotics activate their function which consists in increasing the gene expression of enzymes involved in the metabolism of xenobiotics and detoxication drug transporters. Clarification of these mechanisms enabled the understanding of the substance of many drug-drug interactions observed in the clinical practice. Polymorphism of the nuclear receptors appears to be one of the causes of the interindividual variability in response to drug administration.
7
Klaassen, Curtis D. "Xenobiotic Transporters: Another Protective Mechanism for Chemicals." International Journal of Toxicology 21, no. 1 (January 2002): 7–12. http://dx.doi.org/10.1080/10915810252825975.
Full textAbstract:
Xenobiotic transporters are responsible for the uptake of some chemicals into cells, and extremely important for the export of chemicals out of cells. A number of families of xenobiotic transporters have been cloned the last few years. Some microsomal enzyme inducers will enhance the plasma disappearance and biliary excretion of some xenobiotics that are not biotransformed in the intact animal, as well as in isolated hepatocytes. This is due to an up-regulation of xenobiotic transporters. As a result, some microsomal enzyme inducers will enhance the elimination and decrease the toxicity of some chemicals by enhanced transport.
8
Hatagima, Ana. "Genetic polymorphisms and metabolism of endocrine disruptors in cancer susceptibility." Cadernos de Saúde Pública 18, no. 2 (April 2002): 357–77. http://dx.doi.org/10.1590/s0102-311x2002000200002.
Full textAbstract:
Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered expression of tumor suppressor genes and proto-oncogenes, and nutritional status. Xenobiotic metabolism is the principal mechanism for maintaining homeostasis during the body's exposure to xenobiotics. The balance of xenobiotic absorption and elimination rates in metabolism can be important in the prevention of DNA damage by chemical carcinogens. Thus the ability to metabolize and eliminate xenobiotics can be considered one of the body's first protective mechanisms. Variability in individual metabolism has been related to the enzymatic polymorphisms involved in activation and detoxification of chemical carcinogens. This paper is a contemporary literature review on genetic polymorphisms involved in the metabolism of endocrine disruptors potentially related to cancer development.
9
Tanaka, Atsushi, Patrick SC Leung, and M. Eric Gershwin. "Environmental basis of primary biliary cholangitis." Experimental Biology and Medicine 243, no. 2 (January 2018): 184–89. http://dx.doi.org/10.1177/1535370217748893.
Full textAbstract:
Autoimmunity is a consequence of both genetic and environmental factors, occurring in genetically susceptible hosts with environmental triggers. While genome-wide association studies have revealed a number of susceptible genes contributing to etiology, the environmental triggers remain poorly understood. Primary biliary cholangitis, formally known as primary biliary cirrhosis, is considered a model autoimmune disease for which our group has extensively evaluated environmental factors involved in its etiology. Bacterial infection and xenobiotics have been proposed as candidate environmental factors that may explain tolerance breakdown and production of primary biliary cholangitis-specific antimitochondrial autoantibodies. Large-scale case-control studies have consistently detected an association of primary biliary cholangitis with urinary tract infections caused by Escherichia coli, as E. coli PDC-E2 is molecularly similar to human PDC-E2, the immunodominant target of AMAs. Another bacterium of interest is Novosphingobium aromaticivorans, a ubiquitous xenobiotic-metabolizing bacterium that produces lipoylated proteins, which are highly reactive with sera from primary biliary cholangitis patients. Regarding xenobiotics, case-control studies have suggested that frequent use of nail polish is associated with an increased susceptibility to primary biliary cholangitis. We found that 2-octynamide, the conjugate derived from 2-octynoic acid present in cosmetics, lipsticks, and some chewing gums, was unique in both its quantitative structure–activity relationship analysis and reactivity with primary biliary cholangitis sera. 2-nonyamide is another xenobiotic that also has the optimal chemical structure for xenobiotic modification of the PDC-E2 epitope, as demonstrated by the enhanced epitope recognition with AMA-positive PBC sera. Moreover, we found that C57BL/6 mice immunized with 2-octynoic acid-BSA possess many of the features characteristic to primary biliary cholangitis. Impact statement Autoimmunity is believed to develop in genetically susceptible hosts with triggers from the environment. Researchers have recently demonstrated that bacteria and xenobiotics commonly present in our environment are potential triggers of tolerance breakdown against autoantigens and autoimmunity, particularly in primary biliary cholangitis (PBC). The link between xenobiotics and PBC has been further confirmed with the establishment of PBC model mice by immunizing mice with xenobiotics.
10
Todoruk, Tiona R., and Cooper H. Langford. "Sorption of a Xenobiotic Contaminant in Clean and Petroleum-Contaminated Soil: Roles of Water and Xenobiotic Size." Environmental Chemistry 3, no. 2 (2006): 124. http://dx.doi.org/10.1071/en05082.
Full textAbstract:
Environmental Context.Soil uptake of xenobiotics (e.g. pesticides) can be a complex phenomenon where it is useful to distinguish readily reversible sorption from longer-term retention. A scheme for doing this using fluorescence detection is presented here, along with application to uptake of a model compound in clean and oil-contaminated soils. Both the wetting of the soil and the size of the xenobiotic seem to be important. The present data concern uptake. Desorption is expected to exhibit dependencies on similar factors. The data have implications for understanding persistence. Abstract.Description of sorption of xenobiotics (e.g. pesticides) into soils requires identification of at least two kinetic components. In the present work, the distinction between ‘labile’ (readily reversible) and ‘non-labile’ (not reversible) uptake was extended, introducing a fluorescence-based method using 9-anthracenepropionic acid as a probe molecule. Study of clean, oil-contaminated wettable, and water-repellent oil-contaminated soils has given new perspectives into the role that water plays in xenobiotic uptake. Non-labile uptake is unimportant in the water-repellent soils; however, non-labile components are observed in both clean and wettable oil-contaminated samples, supporting earlier suggestions that water plays a role in non-labile uptake processes. A soil pre-exposed to water exhibited different labile sorption behavior from one where xenobiotic was added simultaneously with water to an air-dried soil. The comparatively rapid non-labile component of uptake (3 days) of 9-anthracenepropanoic acid by a clean soil contrasted with much longer times in earlier studies of 2,4-D and atrazine. This pointed to another factor influencing the sorption phenomenon. Literature data supports a suggestion that the non-labile component of xenobiotic sorption may be more strongly influenced by the size of the xenobiotic than by the structure (e.g. polarity) of the xenobiotic or soil composition.
11
Nakov, Radislav, and Tsvetelina Velikova. "Chemical Metabolism of Xenobiotics by Gut Microbiota." Current Drug Metabolism 21, no. 4 (June 25, 2020): 260–69. http://dx.doi.org/10.2174/1389200221666200303113830.
Full textAbstract:
: Among the gut microbiota’s newly explored roles in human biology is the ability to modify the chemical structures of foreign compounds (xenobiotics). A growing body of evidence has now provided sufficient acumen on the role of the gut microbiota on xenobiotic metabolism, which could have an intense impact on the therapy for various diseases in the future. Gut microbial xenobiotic metabolites have altered bioavailability, bioactivity and toxicity and can intervene with the actions of human xenobiotic-metabolizing enzymes to affect the destiny of other ingested molecules. These modifications are diverse and could lead to physiologically important consequences. : In the current manuscript we aim to review the data currently available on how the gut microbiota directly modifies drugs, dietary compounds, chemicals, pollutants, pesticides and herbal supplements.
12
Rudik, A. V., A. V. Dmitriev, A. A. Lagunin, S. M. Ivanov, D. A. Filimonov, and V. V. Poroikov. "Xenobiotic toxicity prediction combined with xenobiotic metabolism prediction in the human body." Biomeditsinskaya Khimiya 65, no. 2 (2019): 114–22. http://dx.doi.org/10.18097/pbmc20196502114.
Full textAbstract:
The majority of xenobiotics undergo a number of chemical reactions known as biotransformation in human body. The biological activity, toxicity, and other properties of the metabolites may significantly differ from those of the parent compound. Not only xenobiotic itself and its final metabolites produced in large quantities, but the intermediate and final metabolites that are formed in trace quantities, can cause undesirable effects. We have developed a freely available web resource MetaTox (http://www.way2drug.com/mg/) for integral assessment of xenobiotics toxicity taking into account their metabolism in the humans. The generation of the metabolite structures is based on the reaction fragments. The estimates of the probability of the reaction of a certain class and the probability of site of biotransformation are used at the generation of the xenobiotic metabolism pathways. The web resource MetaTox allows researchers to assess the metabolism of compounds in the humans and to obtain assessment of their acute, chronic toxicity, and adverse effects.
13
Sablayrolles, C., A. Breton, C. Vialle, C. Vignoles, and M. Montréjaud-Vignoles. "Priority organic pollutants in the urban water cycle (Toulouse, France)." Water Science and Technology 64, no. 3 (August 1, 2011): 541–56. http://dx.doi.org/10.2166/wst.2011.580.
Full textAbstract:
Application of the European Water Framework Directive requires Member States to have better understanding of the quality of surface waters in order to improve knowledge of priority pollutants. Xenobiotics in urban receiving waters are an emerging concern. This study proposes a screening campaign of nine molecular species of xenobiotics in a separated sewer system. Five sites were investigated over one year in Toulouse (France) using quantitative monitoring. For each sample, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, nonylphenols, diethelhexylphthalate, linear alkylbenzene sulphonates, methyl tert-butylether, total hydrocarbons, estradiol and ethinylestradiol were analysed. Ground, rain and roof collected water concentrations are similar to treated wastewater levels. Run-off water was the most polluted of the five types investigated, discharged into the aquatic environment. The wastewater treatment plant reduced xenobiotic concentrations by 66% before discharge into the environment. Regarding environmental quality standards, observed concentrations in waters were in compliance with standards. The results show that xenobiotic concentrations are variable over time and space in all urban water compartments.
14
Segner, Helmut, and Jean-Pierre Cravedi. "Metabolic Activity in Primary Cultures of Fish Hepatocytes." Alternatives to Laboratory Animals 29, no. 3 (May 2001): 251–57. http://dx.doi.org/10.1177/026119290102900321.
Full textAbstract:
In aquatic toxicology, isolated liver cells from fish can be used as a tool to generate initial information on the hepatic metabolism of xenobiotics, and on the mechanisms of xenobiotic activation or deactivation. This isolation of teleost liver cells is achieved by enzymic dissociation, and monolayer cultures of fish hepatocytes in serum-free medium maintain good viability for 3–8 days. During in vitro culture, fish liver cells express stable levels of phase I and phase II enzymes, such as cytochrome P4501A or glutathione S-transferase, and the cells show an induction of biotransformation enzymes after exposure to xenobiotics. The xenobiotic metabolite pattern produced by fish hepatocytes in vitro is generally similar to that observed in vivo. Limitations to more-intensive application of cultured fish hepatocytes as a screen in aquatic hazard assessment are partly due to the rather limited scope of existing studies, i.e. the focus on one particular species (rainbow trout), and on one particular biotransformation enzyme (cytochrome P4501A), as well as a lack of comparative in vitro/in vivo studies.
15
Negishi, Masahiko, Kaoru Kobayashi, Tsutomu Sakuma, and Tatsuya Sueyoshi. "Nuclear receptor phosphorylation in xenobiotic signal transduction." Journal of Biological Chemistry 295, no. 45 (August 11, 2020): 15210–25. http://dx.doi.org/10.1074/jbc.rev120.007933.
Full textAbstract:
Nuclear pregnane X receptor (PXR, NR1I2) and constitutive active/androstane receptor (CAR, NR1I3) are nuclear receptors characterized in 1998 by their capability to respond to xenobiotics and activate cytochrome P450 (CYP) genes. An anti-epileptic drug, phenobarbital (PB), activates CAR and its target CYP2B genes, whereas PXR is activated by drugs such as rifampicin and statins for the CYP3A genes. Inevitably, both nuclear receptors have been investigated as ligand-activated nuclear receptors by identifying and characterizing xenobiotics and therapeutics that directly bind CAR and/or PXR to activate them. However, PB, which does not bind CAR directly, presented an alternative research avenue for an indirect ligand-mediated nuclear receptor activation mechanism: phosphorylation-mediated signal regulation. This review summarizes phosphorylation-based mechanisms utilized by xenobiotics to elicit cell signaling. First, the review presents how PB activates CAR (and other nuclear receptors) through a conserved phosphorylation motif located between two zinc fingers within its DNA-binding domain. PB-regulated phosphorylation at this motif enables nuclear receptors to form communication networks, integrating their functions. Next, the review discusses xenobiotic-induced PXR activation in the absence of the conserved DNA-binding domain phosphorylation motif. In this case, phosphorylation occurs at a motif located within the ligand-binding domain to transduce cell signaling that regulates hepatic energy metabolism. Finally, the review delves into the implications of xenobiotic-induced signaling through phosphorylation in disease development and progression.
16
Iskandar, Anita R., Florian Martin, Marja Talikka, Walter K. Schlage, Radina Kostadinova, Carole Mathis, Julia Hoeng, and Manuel C. Peitsch. "Systems Approaches Evaluating the Perturbation of Xenobiotic Metabolism in Response to Cigarette Smoke Exposure in Nasal and Bronchial Tissues." BioMed Research International 2013 (2013): 1–14. http://dx.doi.org/10.1155/2013/512086.
Full textAbstract:
Capturing the effects of exposure in a specific target organ is a major challenge in risk assessment. Exposure to cigarette smoke (CS) implicates the field of tissue injury in the lung as well as nasal and airway epithelia. Xenobiotic metabolism in particular becomes an attractive tool for chemical risk assessment because of its responsiveness against toxic compounds, including those present in CS. This study describes an efficient integration from transcriptomic data to quantitative measures, which reflect the responses against xenobiotics that are captured in a biological network model. We show here that our novel systems approach can quantify the perturbation in the network model of xenobiotic metabolism. We further show that this approach efficiently compares the perturbation upon CS exposure in bronchial and nasal epithelial cellsin vivosamples obtained from smokers. Our observation suggests the xenobiotic responses in the bronchial and nasal epithelial cells of smokers were similar to those observed in their respective organotypic models exposed to CS. Furthermore, the results suggest that nasal tissue is a reliable surrogate to measure xenobiotic responses in bronchial tissue.
17
Mathon, Baptiste, Marina Coquery, Cécile Miege, Ywann Penru, and Jean-Marc Choubert. "Removal efficiencies and kinetic rate constants of xenobiotics by ozonation in tertiary treatment." Water Science and Technology 75, no. 12 (March 1, 2017): 2737–46. http://dx.doi.org/10.2166/wst.2017.114.
Full textAbstract:
This study gives a full overview of the chemical oxidation by ozone of selected xenobiotics usually present in effluents of conventional wastewater treatment plants. A qualitative and quantitative overview of literature data was made, and describes the ozonation efficiency and processes for the elimination of 12 xenobiotics (pesticides and pharmaceuticals). A database was built, compiling literature results of experimental ozonation assays in laboratory and real-scale conditions. Special attention was paid to selecting the data and compiling reliable results on removal efficiencies and kinetic parameters. An original study was performed in a semi-batch reactor applying ozone on secondary effluent spiked beforehand with a cocktail of 12 xenobiotics. The results of this study were compared with the literature data to evaluate the influence of the kinetic competition of xenobiotics in spiked wastewater in the determination of kinetic rate constants. These 12 xenobiotics were classified into three groups (high-/medium-/low-oxidizable) according to the ranges of their direct kinetic rate constants (kO3). A best effective ozone dose between 0.2 and 0.4 gO3 gDOC−1 is proposed for the elimination of xenobiotics. The predominant elimination pathway between direct and indirect oxidation was identified for each xenobiotic.
18
Wang, Ning, Sze-Mei Cindy Lau, Gregory Rogers, and Thomas Ray. "A new method for rapid screening of xenobiotic phloem mobility in plants." Functional Plant Biology 27, no. 9 (2000): 835. http://dx.doi.org/10.1071/pp99158.
Full textAbstract:
This paper originates from a presentation at the International Conference on Assimilate Transport and Partitioning, Newcastle, NSW, August 1999 The deposition of hydrophobic polymers in the xylem of wheat grain floral axes prevents water and solute movement into grains via the xylem (xylem discontinuity). The only pathway for translocation of photosynthate or externally applied xenobiotics into wheat grains is via the phloem. We have developed a new method based on the xylem discontinuity for rapidly screening phloem mobility of xenobiotics. By quantifying xenobiotic concentration in grains and excised plants after the compounds were applied through the cut stems, the phloem mobility can be estimated quantitatively. The phloem mobility obtained with our new grain-based method was correlated to xenobiotic chemical properties such as log Kow, pKa and electrical charge, and is consistent with published literature. Phloem mobility values determined by the grain-based assay were correlated to those from the direct phloem sap (aphid stylet exudate) assay of excised and intact plants, indicating that the grain-based assay is as reliable as the direct assay with aphid stylectomy. The new grain-based method is simple, quick, and can be scaled up for rapid screening of xenobiotic phloem mobility in plants. Similar seed (fruit)-based assay could also be developed with wide ranges of plant species that use the phloem as the only pathway for supplying water and nutrients into their seeds or fruits.
19
Fry, Jeffrey R., Michael J. Garle, and Alison H. Hammond. "The Detection of Reactive Metabolites Generated by the Microsomal Mixed Function Oxidase System." Alternatives to Laboratory Animals 16, no. 1 (September 1988): 8–13. http://dx.doi.org/10.1177/026119298801600103.
Full textAbstract:
It is recognised that the cytotoxicity of a number of xenobiotics is mediated through the production of reactive metabolites (1). Given this, and the current emphasis on the development of in vitro tests for assessment of xenobiotic cytotoxicity (2), it is of considerable interest to develop systems for the detection in vitro of cytotoxic reactive metabolites. Indeed, it would seem appropriate to employ a limited battery of tests for detection of xenobiotic-mediated cytotoxicity, some of which would be dedicated to assessment of the role of metabolism in such toxicity. The aim of this review is to identify and discuss the approaches currently being employed to this end, and to suggest some possible future trends.
20
Sobinoff, A. P., V. Pye, B. Nixon, S. D. Roman, and E. A. McLaughlin. "153. XENOBIOTICS; INFLUENCE ON OVARIAN FOLLICULAR DEVELOPMENT." Reproduction, Fertility and Development 21, no. 9 (2009): 71. http://dx.doi.org/10.1071/srb09abs153.
Full textAbstract:
The mammalian female reproductive lifespan is largely defined by a finite pool of ovarian follicles established around the time of birth. It is now understood that certain synthetic chemical compounds, known as xenobiotics, can cause premature ovarian senescence through the destruction of small ovarian follicles. Although the ovotoxic effects of these chemicals are well documented, the exact molecular mechanisms behind their action are only just becoming understood. Recent evidence suggests that bioactivation of xenobiotics by Phase I detoxifying enzymes may lead to the generation of free oxygen radicals (ROS), which we suspect may perturb intracellular signalling pathways in primordial follicles. In this study we attempted to identify ovarian follicle signalling pathways activated by xenobiotic exposure using ovotoxic agents which target immature follicles. Neonatal ovaries obtained from 3/4-day old Swiss mice were exposed to either 4-Vinylcyclohexene (25µM), Methoxychlor (25µM) or Menadione (5µM) for 96hrs using our in vitro culture system. Total RNA was then collected and analysed using Affymetrix Mouse Genome 430 2.0 Arrays. Bioinformatic analysis identified between ~500–1000 genes with a two-fold significant difference in gene expression (p<0.05) for each xenobiotic compared to the control. Differentially expressed genes were analysed for pathways and molecular functions using Ingenuity Pathways Analysis (Ingenuity Systems). In agreement with the current literature, many of the genes belonged to toxic response pathways, such as; Xenobiotic metabolism (10); p53 (15) and Apoptosis (11) signalling. However, the vast majority of the differentially expressed genes belonged to canonical pathways implicated in follicular development, such as PI3K/AKT (18), Wnt/ b -catenin (21), and JAK/Stat (8) signalling. Further qPCR analysis has confirmed a substantial increase in the transcription factor Sox4 and cell cycle inhibitor Cdkn2a in 4-Vinylcyclohexene and Menadione treated ovaries respectively. These results suggest that xenobiotics which target primordial follicles may exert part of their ovotoxic effects by perturbing signalling pathways involved in follicular activation and development.
21
Sonoda, J., and R. M. Evans. "Biological function and mode of action of nuclear xenobiotic receptors." Pure and Applied Chemistry 75, no. 11-12 (January 1, 2003): 1733–42. http://dx.doi.org/10.1351/pac200375111733.
Full textAbstract:
Two related nuclear receptors, the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), act as xenobiotic sensors that protect the body from a multitude of foreign chemicals (xenobiotics) and play a central role in the metabolism and clearance of steroids and toxic endogenous lipids (endobiotics). A structurally diverse array of chemicals including pharmaceutical drugs, steroids, herbal extracts, and pesticides activate PXR or CAR. This activation results in induction of overlapping, but yet distinct drug clearance pathways consisting of cytochrome P450 enzymes, conjugating enzymes, drug transporters, and other related proteins. Similar pathways are also utilized to protect the body from toxic compounds of endogenous origin. Thus, the xenobiotic regulatory circuit contributes both to drug-drug and food-drug interactions as well as endocrine disruption. Consistent with the notion that xenobiotic receptors regulate drug clearance, single nucleotide polymorphisms (SNPs) in either the receptors themselves or receptor-binding sites in the regulatory region of genes encoding metabolic enzymes appear to contribute to the polymorphic expression of components of drug clearance pathways. Together, the xenobiotic receptors PXR and CAR confer metabolic immunity via the ability to control an integrated array of target genes.
22
Moore, Michael N., David M. Lowe, David R. Livingstone, and David R. Dixon. "Molecular and Cellular Indices of Pollutant Effects and Their Use in Environmental Impact Assessment." Water Science and Technology 18, no. 4-5 (April 1, 1986): 223–32. http://dx.doi.org/10.2166/wst.1986.0198.
Full textAbstract:
Marine and estuarine environments receive a wide variety of contaminant chemical (xenobiotic) inputs, which must now be regarded as constituents of the natural system; these xenobiotics tend to over-load the normal physiological mechanisms for their disposal. The credit for the continued survival of organisms must be accorded to the protective mechanisms of biotransfor-mation or detoxication present in cells. These include the NADPH-dependent cytochrome P-450 monooxygenases, which metabolize toxic organic xenobiotics, metallothioneins which bind and detoxify many metals and lysosomal accumulation which sequesters many xenobiotics thus compartmentalizing them away from other cellular components. This presentation considers the development of early-warning systems based on biological responses to cell injury at the molecular, subcellular and cellular levels of organization, with particular emphasis on the use of marine mussels and periwinkles as sentinel organisms for assessing pollutant effects. Responses discussed include those of the microsomal detoxication system to organic xenobiotics, functional and structural responses of lysosomes to organic and inorganic xenobiotics, quantitative structural alterations in the cells of the digestive and reproductive systems and finally genotoxicity measured using aneuploidy and sister chromatid exchange as indices of chromosomal damage. Where possible these indices are discussed in an integrated manner.
23
Karimov, Kh, and Yu Assesorova. "ROLE OF GSTM AND GSTT POLYMORPHIC GENES IN ONCOGENESIS AND THE ONSET OF HEMATOLOGIC NEOPLASMS." Problems in oncology 66, no. 5 (May 1, 2020): 472–78. http://dx.doi.org/10.37469/0507-3758-2020-66-5-472-478.
Full textAbstract:
Throughout life, a person is exposed to various xenobiotics, one of the biological effects of which is the genotoxic effect, leading to the occurrence of oncogenic mutations. Mutagenic and promutagenic substances can be detoxified with the corresponding xenobiotic biotransformation enzymes, however, if the enzymatic activity of the latter changes, the neutralization of the mutagens occurs at a slower pace. The review discusses the polymorphic genes of enzymes of the second phase of the biotransformation of xenobiotics of the GSTS family and presents modern literature data on the role of GSTM and GSTT in oncogenesis and the development of hemoblastoses. The search of scientific literature was carried out using the PubMed and СyberLeninka databases.
24
Majewsky, M., T. Gallé, L. Zwank, and K. Fischer. "Influence of microbial activity on polar xenobiotic degradation in activated sludge systems." Water Science and Technology 62, no. 3 (August 1, 2010): 701–7. http://dx.doi.org/10.2166/wst.2010.925.
Full textAbstract:
The influence of activated sludge quality on the co-metabolic biodegradation of three aminopolycarboxyl acids was investigated for a variety of Luxembourg sewage treatment plants. A combination of biodegradation experiments and respirometric techniques are presented as a reliable approach for the estimation of biokinetics and biological xenobiotic degradation rates that allow for identification of governing parameters such as microbial activity and active biomass. Results showed that biokinetics and degradation rates vary greatly between different plants. The fraction of active biomass on the total suspended solids ranged between 16.9 and 53.7%. Xenobiotic biodegradation rates correlated with microbial activity suggesting a relationship with WWTP performance for carbon and nutrient removal. The biokinetic information can be used to increase the prediction accuracy of xenobiotics removal by individual WWTPs.
25
Ushakov, D. S., T. S. Kalinina, A. S. Dorozhkova, V. Y. Ovchinnikov, and L. F. Gulyaeva. "Tissue-specific effects of benzo[a]pyrene and DDT on microRNA expression profile in female rats." Vavilov Journal of Genetics and Breeding 22, no. 2 (April 8, 2018): 248–55. http://dx.doi.org/10.18699/vj18.355.
Full textAbstract:
Many xenobiotics in the human environment, such as benzo[a]pyrene (B(a)P) and dichlorodiphenyltrichloroethane (DDT), may act as non-genotoxic carcinogens through epigenetic mechanisms, including changes in microRNA expression profile. In part, such disorders can be mediated by the activation of nuclear receptors, resulting in the activation of protein coding gene expression and microRNAs involved in malignant transformation of cells. Therefore, the aim of this study was to investigate the chain of events “xenobiotic administration – receptor activation – up-regulating microRNA expression – down-regulation target genes expression” as one of the key factors in the chemically-induced carcinogenesis. Using in silico methods, an analysis of the rat genome was carried out to find microRNAs putatively regulated by AhR (aryl hydrocarbon receptor) and CAR (constitutive androstane receptor), activated by BP and DDT, respectively. In particular, miR-3577 and -193b were selected as potentially regulated CAR, miR-207 was selected as a candidate for miR under AhR regulation. The results of the study showed that the treatment of female rats with DDT and B(a)P caused a tissue-specific changes in the expression of microRNAs and host genes in both acute and chronic administration of xenobiotics. To confirm the effects of xenobiotics on the microRNA expression, we also estimated the mRNA level of PTPN6, EIF3F, Cbx7, and Dicer1 genes potentially targeting miR-193b, -207, and -3577. The study has shown a high correlation between the expression of target genes and microRNAs; however these changes depended on the tissue types, the dose and time after xenobiotic treatment.
26
Rekka, Eleni A., Panos N. Kourounakis, and Maria Pantelidou. "Xenobiotic Metabolising Enzymes: Impact on Pathologic Conditions, Drug Interactions and Drug Design." Current Topics in Medicinal Chemistry 19, no. 4 (April 11, 2019): 276–91. http://dx.doi.org/10.2174/1568026619666190129122727.
Full textAbstract:
Background: The biotransformation of xenobiotics is a homeostatic defensive response of the body against bioactive invaders. Xenobiotic metabolizing enzymes, important for the metabolism, elimination and detoxification of exogenous agents, are found in most tissues and organs and are distinguished into phase I and phase II enzymes, as well as phase III transporters. The cytochrome P450 superfamily of enzymes plays a major role in the biotransformation of most xenobiotics as well as in the metabolism of important endogenous substrates such as steroids and fatty acids. The activity and the potential toxicity of numerous drugs are strongly influenced by their biotransformation, mainly accomplished by the cytochrome P450 enzymes, one of the most versatile enzyme systems. Objective: In this review, considering the importance of drug metabolising enzymes in health and disease, some of our previous research results are presented, which, combined with newer findings, may assist in the elucidation of xenobiotic metabolism and in the development of more efficient drugs. Conclusion: Study of drug metabolism is of major importance for the development of drugs and provides insight into the control of human health. This review is an effort towards this direction and may find useful applications in related medical interventions or help in the development of more efficient drugs.
27
Miller, David S., Rosalinde Masereeuw, John Henson, and Karl J. Karnaky. "Excretory transport of xenobiotics by dogfish shark rectal gland tubules." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 275, no. 3 (September 1, 1998): R697—R705. http://dx.doi.org/10.1152/ajpregu.1998.275.3.r697.
Full textAbstract:
Marine elasmobranch rectal gland is a specialized, osmoregulatory organ composed of numerous blind-ended, branched tubules emptying into a central duct. To date, NaCl excretion has been its only described function. Here we use isolated rectal gland tubule fragments from dogfish shark ( Squalus acanthias), fluorescent xenobiotics, and confocal microscopy to describe a second function, xenobiotic excretion. Isolated rectal gland tubules rapidly transported the fluorescent organic anion sulforhodamine 101 from bath to lumen. Luminal accumulation was concentrative, saturable, and inhibited by cyclosporin A (CSA), chlorodinitrobenzene, leukotriene C4, and KCN. Inhibitors of renal organic anion transport (probenecid, p-aminohippurate), organic cation transport (tetraethylammonium and verapamil), and P-glycoprotein (verapamil) were without effect. Cellular accumulation of sulforhodamine 101 was not concentrative, saturable, or inhibitable. Rectal gland tubules did not secrete fluorescein, daunomycin, or a fluorescent CSA derivative. Finally, frozen rectal gland sections stained with an antibody to a hepatic canalicular multispecific organic anion transporter (cMOAT or MRP2) showed heavy and specific staining on the luminal membrane of the epithelial cells. We conclude that rectal gland is capable of active and specific excretion of xenobiotics and that such transport is mediated by a shark analog of MRP2, an ATP-driven xenobiotic transporter, but not by P-glycoprotein.
28
Esteves, Francisco, José Rueff, and Michel Kranendonk. "The Central Role of Cytochrome P450 in Xenobiotic Metabolism—A Brief Review on a Fascinating Enzyme Family." Journal of Xenobiotics 11, no. 3 (June 22, 2021): 94–114. http://dx.doi.org/10.3390/jox11030007.
Full textAbstract:
Human Cytochrome P450 (CYP) enzymes constitute a superfamily of membrane-bound hemoproteins that are responsible for the metabolism of a wide variety of clinically, physiologically, and toxicologically important compounds. These heme-thiolate monooxygenases play a pivotal role in the detoxification of xenobiotics, participating in the metabolism of many structurally diverge compounds. This short-review is intended to provide a summary on the major roles of CYPs in Phase I xenobiotic metabolism. The manuscript is focused on eight main topics that include the most relevant aspects of past and current CYP research. Initially, (I) a general overview of the main aspects of absorption, distribution, metabolism, and excretion (ADME) of xenobiotics are presented. This is followed by (II) a background overview on major achievements in the past of the CYP research field. (III) Classification and nomenclature of CYPs is briefly reviewed, followed by (IV) a summary description on CYP’s location and function in mammals. Subsequently, (V) the physiological relevance of CYP as the cornerstone of Phase I xenobiotic metabolism is highlighted, followed by (VI) reviewing both genetic determinants and (VI) nongenetic factors in CYP function and activity. The last topic of the review (VIII) is focused on the current challenges of the CYP research field.
29
Segner, Helmut, Christyn Bailey, Carolina Tafalla, and Jun Bo. "Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?" International Journal of Molecular Sciences 22, no. 17 (August 31, 2021): 9460. http://dx.doi.org/10.3390/ijms22179460.
Full textAbstract:
The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.
30
Schröder, Peter, and Chris Collins. "Conjugating Enzymes Involved in Xenobiotic Metabolism of Organic Xenobiotics in Plants." International Journal of Phytoremediation 4, no. 4 (October 2002): 247–65. http://dx.doi.org/10.1080/15226510208500086.
Full text
31
Sobinoff, A. P., V. Pye, B. Nixon, S. D. Roman, and E. A. McLaughlin. "121. SHORT TERM XENOBIOTIC EXPOSURE COMPROMISES LONG TERM OOCYTE VIABILITY." Reproduction, Fertility and Development 22, no. 9 (2010): 39. http://dx.doi.org/10.1071/srb10abs121.
Full textAbstract:
Mammalian females are born with a finite number of non-renewing primordial follicles, the majority of which remain in a quiescent state for many years. These follicles serve as the primary source of all developing oocytes in the ovary, and cannot be regenerated post fetal development. Due to their non-renewing nature, these “resting” oocytes are particularly vulnerable to environmental and toxic insults, especially to those which are capable of inducing oxidative stress. Recent evidence suggests that certain synthetic chemical compounds, known as xenobiotics, have the potential to generate oxidative stress through the production of free oxygen radicals (ROS) as a byproduct of the cell’s detoxification process. Given the redox sensitive nature of the mammalian oocyte, we hypothesise that xenobiotic exposure may have adverse effects on long term oocyte viability. In this study, we attempted to identify the effects of short term xenobiotic exposure on long term oocyte viability. Female Swiss neonatal mice (day 4) were administered 7 daily consecutive doses of 4-Vinylcyclohexene diepoxide (40mg/kg/daily; 80mg/kg/daily) Methoxychlor (50mg/kg/daily; 100mg/kg/daily) or Menadione (7.5mg/kg/daily; 15mg/kg/daily). Mice were then superovulated at 6wks and their oocytes collected for analysis. Sperm-egg fusion assays revealed a significant decrease (P < 0.01) in sperm egg binding (1.4–7 fold) and fusion (4–20 fold) in a dose dependent manner for all three xenobiotic treatments in vivo, signifying a decrease in oocyte membrane fluidity. Follow-up lipid peroxidation analysis on xenobiotic cultured oocytes also showed a significant (P < 0.01) dose dependent increase (1.3–2.5 fold) in membrane lipid peroxidation for each xenobiotic compared to the control. These results provide some of the first evidence of short term xenobiotic exposure causing long term oocyte dysfunction, possibly interfering with the fluidity and/or elasticity of the oocyte plasma membrane through xenobiotic ROS induced lipid peroxidation.
32
Santiago-Josefat, Belen, Eulalia Pozo-Guisado, Sonia Mulero-Navarro, and Pedro M. Fernandez-Salguero. "Proteasome Inhibition Induces Nuclear Translocation and Transcriptional Activation of the Dioxin Receptor in Mouse Embryo Primary Fibroblasts in the Absence of Xenobiotics." Molecular and Cellular Biology 21, no. 5 (March 1, 2001): 1700–1709. http://dx.doi.org/10.1128/mcb.21.5.1700-1709.2001.
Full textAbstract:
ABSTRACT The aryl hydrocarbon receptor (AHR) is a transcription factor that is highly conserved during evolution and shares important structural features with the Drosophila developmental regulatorsSim and Per. Although much is known about the mechanism of AHR activation by xenobiotics, little information is available regarding its activation by endogenous stimuli in the absence of exogenous ligand. In this study, using embryonic primary fibroblasts, we have analyzed the role of proteasome inhibition on AHR transcriptional activation in the absence of xenobiotics. Proteasome inhibition markedly reduced cytosolic AHR without affecting its total cellular content. Cytosolic AHR depletion was the result of receptor translocation into the nuclear compartment, as shown by transient transfection of a green fluorescent protein-tagged AHR and by immunoblot analysis of nuclear extracts. Gel retardation experiments showed that proteasome inhibition induced transcriptionally active AHR-ARNT heterodimers able to bind to a consensus xenobiotic-responsive element. Furthermore, nuclear AHR was transcriptionally active in vivo, as shown by the induction of the endogenous target gene CYP1A2. Synchronized to AHR activation, proteasome inhibition also induced a transient increase in AHR nuclear translocator (ARNT) at the protein and mRNA levels. Since nuclear levels of AHR and ARNT are relevant for AHR transcriptional activation, our data suggest that proteasome inhibition, through a transient increase in ARNT expression, could promote AHR stabilization and accumulation into the nuclear compartment. An elevated content of nuclear AHR could favor AHR-ARNT heterodimers able to bind to xenobiotic-responsive elements and to induce gene transcription in the absence of xenobiotics. Thus, depending on the cellular context, physiologically regulated proteasome activity could participate in the control of endogenous AHR functions.
33
Kohno, Satomi. "Can Xenobiotics Alter the Sex Ratio of Crocodilians in the Wild?" Sexual Development 15, no. 1-3 (2021): 179–86. http://dx.doi.org/10.1159/000515724.
Full textAbstract:
All crocodilians exhibit temperature-dependent sex determination without sex chromosomes. This temperature dependency can be overridden by exposure to estrogen via estrogen receptor 1. Thus, the sex ratio of crocodilian species is vulnerable to estrogenic xenobiotics. Multiple investigations of the mechanism and effects of xenobiotics in crocodilian species have been conducted since the early 1990s. This review focuses on the impact of xenobiotics on sex determination rather than gonadal functions in crocodilians. The thermosensitive and estrogen-sensitive periods that commit the bipotential gonad to develop as an ovary end by stages 24.5 and 25.3, respectively. In contrast, it is ambiguous when the estrogen-sensitive stage begins for ovarian development, although the thermosensitive period for ovarian development initiates around developmental stage 15 at an extreme female-producing temperature of 30°C. To accurately assess the effect of xenoestrogens on sex ratio in crocodilians, it is critical to collect eggs before the sex-determining period and to incubate them under precisely controlled temperatures. A well-studied system of xenobiotic effects on crocodilians is Lake Apopka (FL, USA), an EPA superfund clean-up site heavily contaminated with Dieldrin, Endrin, and <i>p,p'</i>-DDE. The sum of estimated estrogenicity of xenobiotics measured in Lake Apopka was insufficient to activate the estrogen receptor 1 of <i>Alligator mississippiensis</i>, which is an essential receptor to induce ovarian development. Although juvenile <i>A. mississippiensis</i> showed gonadal alterations in sex hormone production and histology, the environmentally relevant concentration of xenobiotics in Lake Apopka was unlikely to alter the sex ratio of <i>A. mississippiensis.</i> Experimental exposure to xenobiotics such as 17α-ethynylestradiol, <i>p,p'</i>-dichlorodiphenyldichloroethylene, and 2,3,7,8-tetrachlorodibenzodioxin at environmentally relevant concentrations in ovo induced more female offspring in <i>A. mississippiensis</i> as compared with the control group. Bisphenol-A, atrazine, 2,4-dichlorophenoxyacetic acid, endosulfan, and Corexit did not alter the sex ratio of <i>A. mississippiensis</i> or <i>Caiman latirostris</i> under the tested conditions. Egg-incubation temperature has pronounced effects on estrogen sensitivity in crocodilian sex determination. Therefore, crocodilians are vulnerable to xenobiotic contamination and climate change in the wild. It is vital to further investigate the detailed mechanism and effects of environmental xenobiotics in crocodilian sex determination to mitigate their effect on sex ratio and conserve this ancient lineage.
34
Karri, Kritika, and David J. Waxman. "Widespread Dysregulation of Long Noncoding Genes Associated With Fatty Acid Metabolism, Cell Division, and Immune Response Gene Networks in Xenobiotic-exposed Rat Liver." Toxicological Sciences 174, no. 2 (January 11, 2020): 291–310. http://dx.doi.org/10.1093/toxsci/kfaa001.
Full textAbstract:
Abstract Xenobiotic exposure dysregulates hundreds of protein-coding genes in mammalian liver, impacting many physiological processes and inducing diverse toxicological responses. Little is known about xenobiotic effects on long noncoding RNAs (lncRNAs), many of which have important regulatory functions. Here, we present a computational framework to discover liver-expressed, xenobiotic-responsive lncRNAs (xeno-lncs) with strong functional, gene regulatory potential and elucidate the impact of xenobiotic exposure on their gene regulatory networks. We assembled the long noncoding transcriptome of xenobiotic-exposed rat liver using RNA-seq datasets from male rats treated with 27 individual chemicals, representing 7 mechanisms of action (MOAs). Ortholog analysis was combined with coexpression data and causal inference methods to infer lncRNA function and deduce gene regulatory networks, including causal effects of lncRNAs on protein-coding gene expression and biological pathways. We discovered > 1400 liver-expressed xeno-lncs, many with human and/or mouse orthologs. Xenobiotics representing different MOAs often regulated common xeno-lnc targets: 123 xeno-lncs were dysregulated by ≥ 10 chemicals, and 5 xeno-lncs responded to ≥ 20 of the 27 chemicals investigated; 81 other xeno-lncs served as MOA-selective markers of xenobiotic exposure. Xeno-lnc—protein-coding gene coexpression regulatory network analysis identified xeno-lncs closely associated with exposure-induced perturbations of hepatic fatty acid metabolism, cell division, or immune response pathways, and with apoptosis or cirrhosis. We also identified hub and bottleneck lncRNAs, which are expected to be key regulators of gene expression. This work elucidates extensive networks of xeno-lnc—protein-coding gene interactions and provides a framework for understanding the widespread transcriptome-altering actions of foreign chemicals in a key-responsive mammalian tissue.
35
Bu, Chunya, Jinling Li, Xiao-Qin Wang, Guanglu Shi, Bo Peng, Jingyu Han, Pin Gao, and Younian Wang. "Transcriptome Analysis of the Carmine Spider Mite,Tetranychus cinnabarinus(Boisduval, 1867) (Acari: Tetranychidae), and Its Response toβ-Sitosterol." BioMed Research International 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/794718.
Full textAbstract:
Tetranychus cinnabarinus(Acari: Tetranychidae) is a worldwide polyphagous agricultural pest that has the title of resistance champion among arthropods. We reported previously the identification of the acaricidal compoundβ-sitosterol fromMentha piperitaandInula japonica. However, the acaricidal mechanism ofβ-sitosterol is unclear. Due to the limited genetic research carried out, wede novoassembled the transcriptome ofT. cinnabarinususing Illumina sequencing and conducted a differential expression analysis of control andβ-sitosterol-treated mites. In total, we obtained >5.4 G high-quality bases for each sample with unprecedented sequencing depth and assembled them into 22,941 unigenes. We identified 617 xenobiotic metabolism-related genes involved in detoxification, binding, and transporting of xenobiotics. A highly expanded xenobiotic metabolic system was found in mites.T. cinnabarinusdetoxification genes—including carboxyl/cholinesterase and ABC transporter class C—were upregulated afterβ-sitosterol treatment. Defense-related proteins, such as Toll-like receptor, legumain, and serine proteases, were also activated. Furthermore, other important genes—such as the chloride channel protein, cytochromeb, carboxypeptidase, peritrophic membrane chitin binding protein, and calphostin—may also play important roles in mites’ response toβ-sitosterol. Our results demonstrate that high-throughput-omics tool facilitates identification of xenobiotic metabolism-related genes and illustration of the acaricidal mechanisms ofβ-sitosterol.
36
Mogilenkova, Lyubov A., and V. R. Rembovskiy. "Role of genetic polymorphism and differences in the detoxification of chemical substances in the human body." Hygiene and sanitation 95, no. 3 (October 28, 2019): 255–62. http://dx.doi.org/10.18821/0016-9900-2016-95-3-255-262.
Full textAbstract:
There are given modern views on the role of genetic polymorphism on the detoxification of chemical substances and individual sensitivity in workers to the development of diseases associated with xenobiotics metabolism disorders. In the search for genetic markers of occupationally caused diseases it is promising to study allelomorphs of genes responsible for the polyfunctional response of the human body, including genes involved in xenobiotic biotransformation. There is substantiated the expediency of compilation and introduction of genetic passports for stuff occupied at hazardous chemical enterprises.
37
Oesch, F., E. Fabian, and Robert Landsiedel. "Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models." Archives of Toxicology 93, no. 12 (October 31, 2019): 3419–89. http://dx.doi.org/10.1007/s00204-019-02602-7.
Full textAbstract:
Abstract The xenobiotic metabolism in the lung, an organ of first entry of xenobiotics into the organism, is crucial for inhaled compounds entering this organ intentionally (e.g. drugs) and unintentionally (e.g. work place and environmental compounds). Additionally, local metabolism by enzymes preferentially or exclusively occurring in the lung is important for favorable or toxic effects of xenobiotics entering the organism also by routes other than by inhalation. The data collected in this review show that generally activities of cytochromes P450 are low in the lung of all investigated species and in vitro models. Other oxidoreductases may turn out to be more important, but are largely not investigated. Phase II enzymes are generally much higher with the exception of UGT glucuronosyltransferases which are generally very low. Insofar as data are available the xenobiotic metabolism in the lung of monkeys comes closed to that in the human lung; however, very few data are available for this comparison. Second best rate the mouse and rat lung, followed by the rabbit. Of the human in vitro model primary cells in culture, such as alveolar macrophages and alveolar type II cells as well as the A549 cell line appear quite acceptable. However, (1) this generalization represents a temporary oversimplification born from the lack of more comparable data; (2) the relative suitability of individual species/models is different for different enzymes; (3) when more data become available, the conclusions derived from these comparisons quite possibly may change.
38
Che, Xun, and Wei Dai. "Aryl Hydrocarbon Receptor: Its Regulation and Roles in Transformation and Tumorigenesis." Current Drug Targets 20, no. 6 (March 29, 2019): 625–34. http://dx.doi.org/10.2174/1389450120666181109092225.
Full textAbstract:
AhR is an environmental response gene that mediates cellular responses to a variety of xenobiotic compounds that frequently function as AhR ligands. Many AhR ligands are classified as carcinogens or pro-carcinogens. Thus, AhR itself acts as a major mediator of the carcinogenic effect of many xenobiotics in vivo. In this concise review, mechanisms by which AhR trans-activates downstream target gene expression, modulates immune responses, and mediates malignant transformation and tumor development are discussed. Moreover, activation of AhR by post-translational modifications and crosstalk with other transcription factors or signaling pathways are also summarized.
39
Foroozesh, Maryam, Jayalakshmi Sridhar, Navneet Goyal, and Jiawang Liu. "Coumarins and P450s, Studies Reported to-Date." Molecules 24, no. 8 (April 24, 2019): 1620. http://dx.doi.org/10.3390/molecules24081620.
Full textAbstract:
Cytochrome P450 enzymes (CYPs) are important phase I enzymes involved in the metabolism of endogenous and xenobiotic compounds mainly through mono-oxygenation reactions into more polar and easier to excrete species. In addition to their role in detoxification, they play important roles in the biosynthesis of endogenous compounds and the bioactivation of xenobiotics. Coumarins, phytochemicals abundant in food and commonly used in fragrances and cosmetics, have been shown to interact with P450 enzymes as substrates and/or inhibitors. In this review, these interactions and their significance in pharmacology and toxicology are discussed in detail.
40
MUANGMOONCHAI, Roongsiri, Despina SMIRLIS, Siew-Cheng WONG, Mina EDWARDS, Ian R. PHILLIPS, and Elizabeth A. SHEPHARD. "Xenobiotic induction of cytochrome P450 2B1 (CYP2B1) is mediated by the orphan nuclear receptor constitutive androstane receptor (CAR) and requires steroid co-activator 1 (SRC-1) and the transcription factor Sp1." Biochemical Journal 355, no. 1 (February 26, 2001): 71–78. http://dx.doi.org/10.1042/bj3550071.
Full textAbstract:
The constitutive androstane receptor (CAR) activates the expression of a reporter gene attached to the phenobarbital-response element (PBRE) of the cytochrome P450 2B1 (CYP2B1) gene in response to the barbiturate phenobarbital and the plant product picrotoxin. The xenobiotic-mediated increase in transactivation occurs in transfected primary hepatocytes and in liver transfected by biolistic-particle-mediated DNA transfer, but not in the transformed cell lines HepG2, CV-1 and HeLa, which support only constitutive activation of gene expression by CAR. Steroid co-activator 1 (SRC-1) enhances both constitutive and xenobiotic-induced CAR-mediated transactivation via the CYP2B1 PBRE in transfected primary hepatocytes. The nuclear receptor 1 (NR1) site of the PBRE is sufficient for CAR-mediated transactivation, but additional sequences within the PBRE, and hence the proteins that bind to them, are required for the interaction of CAR with SRC-1. The NR2 site of the PBRE binds proteins other than CAR, including an unidentified nuclear receptor heterodimerized with retinoid X receptor α. By binding to the proximal promoter of CYP2B1, the transcription factor Sp1 increases both basal transcription and xenobiotic-induced expression via the PBRE. Thus induction of CYP2B1 expression by xenobiotics is mediated by the nuclear receptor CAR and, for optimal expression, requires SRC-1 and Sp1.
41
Sarmiento, Marjorie Raquel Anariba, Thais Oliveira de Paula, Francis Moreira Borges, Alessandra Barbosa Ferreira-Machado, Juliana Alves Resende, Ana Paula Boroni Moreira, Sheila Cristina Potente Dutra Luquetti, Dioneia Evangelista Cesar, Vânia Lúcia da Silva, and Claudio Galuppo Diniz. "Obesity, Xenobiotic Intake and Antimicrobial-Resistance Genes in the Human Gastrointestinal Tract: A Comparative Study of Eutrophic, Overweight and Obese Individuals." Genes 10, no. 5 (May 7, 2019): 349. http://dx.doi.org/10.3390/genes10050349.
Full textAbstract:
Although lifestyle and physiology in obese individuals are accepted to lead to changes in the intestinal microbiota, uncertainty remains about microbiota dysbiosis, and xenobiotics intake, as a source of selective pressure, independent of antimicrobial chemotherapy. The aim of this study was to compare the occurrence of antimicrobial resistance genetic markers (ARG) in faecal specimens of eutrophic, overweight and obese individuals, and their correlation with xenobiotic intake and gut bacteria density. Methods: This was a cross-sectional case-controlled study including 72 adult participants with no record of intestinal or systemic diseases, or recent use of antimicrobials, grouped as eutrophic, overweight, or obese. Anthropometric profile, eating habits and oral xenobiotics intake were recorded. Faecal metagenomic DNA was used to screen for ARG by PCR, and to measure bacterial groups by fluorescence in situ hybridization (FISH). Student’s t and Wilcoxon tests were used to compare means and differences in ARG detection (95% confidence intervals). Correlation analyses (odds ratio) and relationships between bacteria density and ARG were determined. Results: Increase in abdominal circumference, waist circumference, hip, waist-hip ratio, BMI, carbohydrate, fibres, and total calorie intakes were different from eutrophic to obese participants. Habitual use of antihypertensive and anti-inflammatory drugs, antacids, and artificial sweeteners were associated mainly with obesity and overweight. Nutritional supplements were associated to the eutrophic group. ARG screening showed differences being more frequent among obese, and positive for 27 genetic markers related to β-lactams, tetracyclines, the macrolide lincosamide and streptogramin group, quinolones, sulfonamides, aminoglycosides, and efflux pump. Positive correlation between ARG and BMI, caloric intake, and intake of xenobiotics, was observed for obese individuals. Relationships among ARG detection and bacteria densities were also different. Conclusions: This study reinforces the hypothesis that obese individuals may harbour an altered gut microbiota, if compared to eutrophic. The overweight individuals display a transitional gut microbiota which seems to be between eutrophic and obese. Furthermore, the increased xenobiotic intake associated to obesity may play an important role in the antimicrobial resistance phenomenon.
42
Reddy, Janardan K., M. Sambasiva Rao, and Anjana V. Yeldandi. "Peroxisome Proliferation: A Biological Marker for Toxicological Evaluation." Journal of the American College of Toxicology 11, no. 3 (May 1992): 349–52. http://dx.doi.org/10.3109/10915819209141874.
Full textAbstract:
Peroxisome proliferators constitute an important group of xenobiotics with therapeutic, societal, and agricultural importance. Because these agents induce liver tumors in rodents, but fail to exert the genotoxic or mutagenic effects directly in short-term in vitro test systems, they are considered a paradigm to investigate the mechanisms of nongenotoxic hepatocarcinogenesis. A concerted cell biological, biochemical, and molecular biological approach is essential to understand the relationship of xenobiotic-induced peroxisome proliferation to the eventual development of liver tumors. It is our intent to provide insight into the mechanisms responsible for tissue specificity and species differences in the biological responses to peroxisome proliferators.
43
Wright, M. C. "The impact of pregnane X receptor activation on liver fibrosis." Biochemical Society Transactions 34, no. 6 (October 25, 2006): 1119–23. http://dx.doi.org/10.1042/bst0341119.
Full textAbstract:
The PXR (pregnane X receptor) is a nuclear receptor transcription factor that is activated by a range of endobiotics and xenobiotics. The activated PXR modulates the transcription of genes in hepatocytes (the main functional cell of the liver) associated with endobiotic and xenobiotic uptake, metabolism and excretion. However, activation of the PXR also inhibits a deleterious response of the liver to chronic damage – that of fibrosis. The antifibrogenic mode of action is mediated through changes in the expression of genes in hepatic stellate cells and liver macrophages (Kupffers). These results suggest an additional function for the PXR.
44
Tabb, Michelle M., and Bruce Blumberg. "New Modes of Action for Endocrine-Disrupting Chemicals." Molecular Endocrinology 20, no. 3 (March 1, 2006): 475–82. http://dx.doi.org/10.1210/me.2004-0513.
Full textAbstract:
Abstract Endocrine-disrupting chemicals (EDC) are commonly considered to be compounds that mimic or block the transcriptional activation elicited by naturally circulating steroid hormones by binding to steroid hormone receptors. For example, the Food Quality Protection Act of 1996 defines EDC as those, that “may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effect as the Administrator may designate.” The definition of EDC was later expanded to include those that act on the estrogen, androgen, and thyroid hormone receptors. In this minireview, we discuss new avenues through which xenobiotic chemicals influence these and other hormone-dependent signaling pathways. EDC can increase or block the metabolism of naturally occurring steroid hormones and other xenobiotic chemicals by activating or antagonizing nuclear hormone receptors. EDC affect the transcriptional activity of nuclear receptors by modulating proteasome-mediated degradation of nuclear receptors and their coregulators. Xenobiotics and environmental contaminants can act as hormone sensitizers by inhibiting histone deacetylase activity and stimulating mitogen-activated protein kinase activity. Some endocrine disrupters can have genome-wide effects on DNA methylation status. Others can modulate lipid metabolism and adipogenesis, perhaps contributing to the current epidemic of obesity. Additional elucidation of these new modes of endocrine disruption will be key in understanding the nature of xenobiotic effects on the endocrine system.
45
Sui, Yipeng, Zhaojie Meng, Se-Hyung Park, Weiwei Lu, Christopher Livelo, Qi Chen, Tong Zhou, and Changcheng Zhou. "Myeloid-specific deficiency of pregnane X receptor decreases atherosclerosis in LDL receptor-deficient mice." Journal of Lipid Research 61, no. 5 (March 13, 2020): 696–706. http://dx.doi.org/10.1194/jlr.ra119000122.
Full textAbstract:
The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXRΔMyeLDLR−/−) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXRΔMyeLDLR−/− mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXRΔMyeLDLR−/− mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management.
46
Williams, Michael J., Lyle Wiemerslage, Priya Gohel, Sania Kheder, Lakshmi V. Kothegala, and Helgi B. Schiöth. "Dibutyl Phthalate Exposure Disrupts Evolutionarily Conserved Insulin and Glucagon-Like Signaling in Drosophila Males." Endocrinology 157, no. 6 (April 21, 2016): 2309–21. http://dx.doi.org/10.1210/en.2015-2006.
Full textAbstract:
Phthalate diesters are commonly used as industrial plasticisers, as well as in cosmetics and skin care products, as a result people are constantly exposed to these xenobiotics. Recent epidemiological studies have found a correlation between circulating phthalate levels and type 2 diabetes, whereas animal studies indicate that phthalates are capable of disrupting endocrine signaling. Nonetheless, how phthalates interfere with metabolic function is still unclear. Here, we show that feeding Drosophila males the xenobiotic dibutyl phthalate (DBP) affects conserved insulin- and glucagon-like signaling. We report that raising flies on food containing DBP leads to starvation resistance, increased lipid storage, hyperglycemia, and hyperphagia. We go on to show that the starvation-resistance phenotype can be rescued by overexpression of the glucagon analogue adipokinetic hormone (Akh). Furthermore, although acute DBP exposure in adult flies is able to affect insulin levels, only chronic feeding influences Akh expression. We establish that raising flies on DBP-containing food or feeding adults DBP food affects the expression of homologous genes involved in xenobiotic and lipid metabolism (AHR [Drosophila ss], NR1I2 [Hr96], ABCB1 [MDR50], ABCC3 [MRP], and CYP3A4 [Cyp9f2]). Finally, we determined that the expression of these genes is also influenced by Akh. Our results provide comprehensive evidence that DBP can disrupt metabolism in Drosophila males, by regulating genes involved in glucose, lipid, and xenobiotic metabolism.
47
Küblbeck, Jenni, Jonna Niskanen, and Paavo Honkakoski. "Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR." Cells 9, no. 10 (October 15, 2020): 2306. http://dx.doi.org/10.3390/cells9102306.
Full textAbstract:
During the last two decades, the constitutive androstane receptor (CAR; NR1I3) has emerged as a master activator of drug- and xenobiotic-metabolizing enzymes and transporters that govern the clearance of both exogenous and endogenous small molecules. Recent studies indicate that CAR participates, together with other nuclear receptors (NRs) and transcription factors, in regulation of hepatic glucose and lipid metabolism, hepatocyte communication, proliferation and toxicity, and liver tumor development in rodents. Endocrine-disrupting chemicals (EDCs) constitute a wide range of persistent organic compounds that have been associated with aberrations of hormone-dependent physiological processes. Their adverse health effects include metabolic alterations such as diabetes, obesity, and fatty liver disease in animal models and humans exposed to EDCs. As numerous xenobiotics can activate CAR, its role in EDC-elicited adverse metabolic effects has gained much interest. Here, we review the key features and mechanisms of CAR as a xenobiotic-sensing receptor, species differences and selectivity of CAR ligands, contribution of CAR to regulation hepatic metabolism, and evidence for CAR-dependent EDC action therein.
48
Lee, Mi R., Yeon J. Kim, Dae Y. Hwang, Tae S. Kang, Jin H. Hwang, Chae H. Lim, Hyung K. Kang, et al. "An In Vitro Bioassay for Xenobiotics Using the SXR-Driven Human CYP3A4/lac Z Reporter Gene." International Journal of Toxicology 22, no. 3 (May 2003): 207–13. http://dx.doi.org/10.1080/10915810305110.
Full textAbstract:
The dose and time effect of nine xenobiotics, including 17β-estradiol, corticosterone, dexamethasone, progesterone, nifedipine, bisphenol A, rifampicin, methamphetamine, and nicotine were investigated, in vitro, using human steroid and xenobiotics receptor (SXR)-binding sites on the human CYP3A4 promoter, which can enhance the linked lac Z reporter gene transcription. To test this, liver-specific SAP (human serum amyloid P component)-SXR (SAP/SXR) and human CYP3A4 promoter-regulated lac Z (h CYP3A4/lac Z) constructs were transiently transfected into Hep G2 and NIH3T3 cells to compare the xenobiotic responsiveness between human and nonhuman cell lines. In the Hep G2 cells, rifampicin, followed by corticosterone, nicotine, methamphetamine, and dexamethasone, exhibited enhanced levels of the lac Z transcript, whereas those of bisphenol A and nifedipine were found to be reduced. No significant responses were observed with 17β-estradiol or progesterone. In addition, 17β-estradiol and progesterone did not change the levels of the lac Z transcripts in the Hep G2 cells, but did induce significant increases in the transcripts of the NIH3T3 cells. Treatment with corticosterone and dexamethasone, which were highly expressed in the Hep G2 cells, did not affect the levels of the lac Z transcript in NIH3T3 cells. These results show that lac Z transcripts can be measured, rapidly and reproducibly, using reverse transcriptase–polymerase chain reaction (RT-PCR) based on the expression of the h CYP3A4/lac Z reporter gene, and was mediated by the SXR. Thus, this in vitro reporter gene bioassay is useful for measuring xenobiotic activities, and is a means to a better relevant bioassay, using human cells, human genes and human promoters, in order to get a closer look at actual human exposure.
49
Mijanović, Mirjana, and Asija Začiragić. "Comparative Determination of Xenobiotics Adsorption." Bosnian Journal of Basic Medical Sciences 6, no. 3 (August 20, 2006): 54–56. http://dx.doi.org/10.17305/bjbms.2006.3145.
Full textAbstract:
Xenobiotic solutions of different concentrations were analyzed by TLC method before and after passing trough the column with adsorbent M and compared with adsorption on the active charcoal. The efficiency of adsorption on adsorbent M was higher, compared to active charcoal. The best adsorption, in the value 90 - 100%, have shown certain organochlorine and organophosphorus pesticides, that were dissolved in non-aqueous solvents. Efficiency of adsorbent M was also proven in vivo, when solutions of tested xenobiotics before adsorption have caused death of experimental animals, and after the adsorption on adsorbent M, all treated animals have survived and had just mild symptoms of poisoning.
50
Fonseca, Elza S. S., Raquel Ruivo, André M. Machado, Francisca Conrado, Boon-Hui Tay, Byrappa Venkatesh, Miguel M. Santos, and L. Filipe C. Castro. "Evolutionary Plasticity in Detoxification Gene Modules: The Preservation and Loss of the Pregnane X Receptor in Chondrichthyes Lineages." International Journal of Molecular Sciences 20, no. 9 (May 10, 2019): 2331. http://dx.doi.org/10.3390/ijms20092331.
Full textAbstract:
To appraise how evolutionary processes, such as gene duplication and loss, influence an organism’s xenobiotic sensitivity is a critical question in toxicology. Of particular importance are gene families involved in the mediation of detoxification responses, such as members of the nuclear receptor subfamily 1 group I (NR1I), the pregnane X receptor (PXR), and the constitutive androstane receptor (CAR). While documented in multiple vertebrate genomes, PXR and CAR display an intriguing gene distribution. PXR is absent in birds and reptiles, while CAR shows a tetrapod-specific occurrence. More elusive is the presence of PXR and CAR gene orthologs in early branching and ecologically-important Chondrichthyes (chimaeras, sharks and rays). Therefore, we investigated various genome projects and use them to provide the first identification and functional characterization of a Chondrichthyan PXR from the chimaera elephant shark (Callorhinchus milii, Holocephali). Additionally, we substantiate the targeted PXR gene loss in Elasmobranchii (sharks and rays). Compared to other vertebrate groups, the chimaera PXR ortholog displays a diverse expression pattern (skin and gills) and a unique activation profile by classical xenobiotic ligands. Our findings provide insights into the molecular landscape of detoxification mechanisms and suggest lineage-specific adaptations in response to xenobiotics in gnathostome evolution.