Journal articles: 'In vivo toxicity studies'

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Nikitin, Alexander, Yi Wang, and Emmanuel Giannelis. "In vivo toxicity studies of nanoparticles." Toxicology Letters 180 (October 2008): S222. http://dx.doi.org/10.1016/j.toxlet.2008.06.094.

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Attarde, Saurabh S., and Sangeeta V. Pandit. "In Vivo Toxicity Profile of NN-32 and Nanogold Conjugated GNP-NN-32 from Indian Spectacled Cobra Venom." Current Pharmaceutical Biotechnology 21, no. 14 (2020): 1479–88. http://dx.doi.org/10.2174/1389201021666200519101221.

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Background: NN-32 toxin, which was obtained from Naja naja venom and showed cytotoxicity on cancer cell lines. As the toxicity of NN-32 is the main hurdle in the process of drug development; hence, we have conjugated NN-32 toxin with gold nanoparticles (GNP-NN-32) in order to decrease the toxicity of NN-32 without reducing its efficacy, GNP-NN-32 alleviated the toxicity of NN-32 in in vitro studies during the course of earlier studies. In continuation, we are evaluating in vivo toxicity profile of NN-32 and GNP-NN-32 in the present study. Objective: To study in vivo toxicity profile of NN-32 and nanogold conjugated GNP-NN-32 from Naja naja venom. Materials and Methods: We have carried out in vivo acute toxicity study to determine LD50 dose of GNP-NN-32, in vivo sub-chronic toxicity for 30 days, haematology, serum biochemical parameters and histopathology study on various mice tissues and in vitro cellular and tissue toxicity studies. Results: The LD50 dose of GNP-NN-32 was found to be 2.58 mg/kg (i.p.) in Swiss male albino mice. In vivo sub-chronic toxicity showed significantly reduced toxicity of GNP-NN-32 as compared to NN-32 alone. Discussion: In vitro cellular toxicity studies on human lymphocyte and mouse peritoneal macrophage showed significant inhibition of cells by NN-32 alone. Conclusion: Conjugated GNP-NN-32 toxin showed less in vivo toxicity as compared to pure NN-32.

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Samuel, P., B. Pavithra, R. Priyadarshini, V. Maheswari, J. Vijayakumar, and T. Selvarathinam. "TOXICITY STUDIES ON SILVER AND COPPER NANOPARTICLES." INDIAN DRUGS 55, no. 09 (2018): 58–60. http://dx.doi.org/10.53879/id.55.09.11399.

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In a pilot scale study, silver and copper nanoparticles were synthesized from two different plant sources viz Flacourtia indica and Prosopsis juliflora. The in vivo toxicity of silver and copper nanoparticles was tested on Danio rerio (Zebra fish) under different concentrations (1 ppm, 10 ppm and 100 ppm). Through the investigation, the nanoparticles treated fishes developed with hyper pigmentation in the ventral region. The minimum lethal concentration required to bring lethality caused by silver nanoparticle was 10 ppm whereas for copper nanoparticles it was 1 ppm. Further, the concentration of silver and copper nanoparticles accumulated inside the fish was evaluated by Atomic Absorption Spectroscopy. The in vivo concentration of silver and copper nanoparticles steadily increases with increase in dosage of nanoparticles being tested.

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Dorgelo, Folke O., Erik Biessen, and Gerrit M. Alink. "Are Cultured Neonatal Rat Heart Cells a Suitable Model for Predicting Acute and Chronic Toxicity In Vivo?" Alternatives to Laboratory Animals 14, no. 1 (1986): 14–22. http://dx.doi.org/10.1177/026119298601400104.

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Beating heart cells isolated from neonatal rats were used in an in vitro assay for testing the influence of chemical compounds on beating frequency. Half of the studied compounds had a no-effect level (NEL) in vivo based on changes in body weight or organ weight. Correlations were obtained between in vivo parameters such as LD50 values in acute toxicity studies and NELs in chronic toxicity studies, and in vitro parameters such as reduction in beating frequency and arrest of contraction. The in vitro parameters correlated well with in vivo LD50 values, but poorly with NELs in vivo.

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Lien Nghiem, Thi Ha, Thi Tuyen Nguyen, Emmanuel Fort, et al. "Capping and in vivo toxicity studies of gold nanoparticles." Advances in Natural Sciences: Nanoscience and Nanotechnology 3, no. 1 (2012): 015002. http://dx.doi.org/10.1088/2043-6262/3/1/015002.

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Ellis, HJ, and PJ Ciclitira. "In vivo gluten challenge in coeliac disease." Canadian Journal of Gastroenterology 15, no. 4 (2001): 243–47. http://dx.doi.org/10.1155/2001/127241.

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In vivo gluten challenge has been used since the early 1950s to study the role of cereal fractions in celiac disease. While early studies relied on crude indicators of celiac toxicity, the advent of jejunal biopsy and sophisticated immunohistochemical techniques has allowed accurate studies to be performed. Studies to determine the nature of the cereal component that is toxic to patients with celiac disease have concentrated on wheat because of its nutritional importance. A number of in vitro studies indicated the presence of one or more celiac-activating epitopes with theN-terminus of the A-gliadin molecule. In vivo challenge with three synthetic peptides subsequently indicated the toxicity of a peptide corresponding to amino acids 31 to 49 of A-gliadin. In vivo gluten challenge is the gold standard for the assessment of celiac toxicity; however, jejunal biopsy is a relatively invasive procedure, thus, other methods have been investigated. Direct infusion of the rectum with gluten has been shown to result in an increase in mucosal intraepithelial lymphocytes, occurring only in celiac patients. This method has been used to study the celiac toxicity of gliadin subfractions. The in vitro technique of small intestinal biopsy organ culture is also a useful tool and appears to give the same results as in vivo challenge. The importance of tiny amounts of gliadin in the diet, such as that which occurs in wheat starch, has been studied by in vivo challenge; this technique has clarified the position of oats in the gluten-free diet. Several studies suggest that this cereal may be included in the diet of most adult celiac patients. Studies of the transport of gliadin across the enterocyte following ingestion or challenge suggest that gliadin may be metabolized by a different pathway in celiac disease. This could result in an abnormal presentation to the immune system, triggering a pathogenic rather than a tolerogenic response.

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Mangla, Bharti, Yub R. Neupane, Archu Singh, Pankaj Kumar, Sadat Shafi, and Kanchan Kohli. "Lipid-nanopotentiated combinatorial delivery of tamoxifen and sulforaphane: ex vivo, in vivo and toxicity studies." Nanomedicine 15, no. 26 (2020): 2563–83. http://dx.doi.org/10.2217/nnm-2020-0277.

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Aim: This study aims to load tamoxifen (TAM) and sulforaphane (SFN) into nanostructured lipid carriers (NLCs) to enhance their oral delivery. Materials & methods: TAM-SFN-NLCs were prepared using Precirol® ATO5 and Transcutol® HP, characterized and evaluated in vitro and ex vivo to assess the drug release profile and intestinal permeability, respectively. In vivo pharmacokinetic and acute toxicity assessment was performed in Wistar rats. Results: Optimized TAM-SFN-NLCs exhibited a particle size of 121.9 ± 6.42 nm and zeta potential of -21.2 ± 2.91 mV. The NLCs enhanced intestinal permeability of TAM and SFN and augmented oral bioavailability of TAM and SFN 5.2-fold and 4.8-fold, respectively. SFN significantly reduced TAM-associated toxicity in vivo. Conclusion: This coencapsulation of a chemotherapeutic agent with a herbal bioactive in NLCs could pave a novel treatment approach against cancer.

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Hendrickson, O. D., A. V. Zherdev, I. V. Gmoshinskii, and B. B. Dzantiev. "Fullerenes: In vivo studies of biodistribution, toxicity, and biological action." Nanotechnologies in Russia 9, no. 11-12 (2014): 601–17. http://dx.doi.org/10.1134/s199507801406010x.

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Patra, Chitta Ranjan, Soha S. Abdel Moneim, Enfeng Wang, et al. "In vivo toxicity studies of europium hydroxide nanorods in mice." Toxicology and Applied Pharmacology 240, no. 1 (2009): 88–98. http://dx.doi.org/10.1016/j.taap.2009.07.009.

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Yoladi, Fatma Betül, Edanur Burmaoğlu, and Şaziye Sezin Palabiyik Yücelik. "Experimental In Vivo Toxicity Models for Alcohol Toxicity." Eurasian Journal of Medicine 55, S1 (2024): 82–90. http://dx.doi.org/10.5152/eurasianjmed.2023.23345.

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Romero-Castillo, L., I. Posadas, and V. Ceña. "Exploring the in vivo toxicity of nanoparticles." Canadian Journal of Chemistry 95, no. 9 (2017): 917–26. http://dx.doi.org/10.1139/cjc-2017-0203.

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Toxicological tests of a xenobiotic play a key role to determine the safety of the new compound before it reaches the market. In this review article, we describe the main types of toxicological studies that can be performed in vivo to detect a possible undesired effect of a xenobiotic with especial emphasis on the data available for the different types of nanoparticles. The different procedures described in this review allow to obtain valuable information about the possible toxic effects of a xenobiotic to minimize the possible risks for patients once the compound has been approved for therapeutic use.

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Calzada, Fernando, Elihú Bautista, Sergio Hidalgo-Figueroa, et al. "Antilymphoma Effect of Incomptine A: In Vivo, In Silico, and Toxicological Studies." Molecules 26, no. 21 (2021): 6646. http://dx.doi.org/10.3390/molecules26216646.

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Incomptine A (IA) is a sesquiterpene lactone isolated from Decachaeta incompta that induces apoptosis, reactive oxygen species production, and a differential protein expression on the U-937 (diffuse histiocytic lymphoma) cell line. In this work, the antitumor potential of IA was investigated on Balb/c mice inoculated with U-937 cells and through the brine shrimp lethality (BSL) test. Furthermore, IA was subjected to molecular docking study using as targets proteins associated with processes of cancer as apoptosis, oxidative stress, and glycolytic metabolism. In addition to determining the potential toxicity of IA in human, its acute toxicity was performed in mice. Results reveals that IA showed high antilymphoma activity and BSL with an EC50 of 2.4 mg/kg and LC50 16.7 µg/mL, respectively. The molecular docking study revealed that IA has strong interaction on all targets used. In the acute oral toxicity, IA had a LD50 of 149 mg/kg. The results showed that the activities of IA including antilymphoma activity, BSL, acute toxicity, and in silico interactions were close to the methotrexate, an anticancer drug used as positive control. These findings suggest that IA may serve as a candidate for the development of a new drug to combat lymphoma.

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Revathi, Sundaramoorthy, V. Gopal, and G. Jeyabalan. "ACUTE TOXICITY AND IN-VIVO LAXATIVE STUDIES OF THE TRIPHALA EXTRACT IN EXPERIMENTAL ANIMALS." Journal of Drug Delivery and Therapeutics 9, no. 4 (2019): 341–47. http://dx.doi.org/10.22270/jddt.v9i4.3170.

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Triphala has been extensively used in traditional medicine for laxative, antidiabetic, expectorant, astringent, anti-aging etc. The acute toxicity of methanolic extracts of Triphala in 300 mg, 600 mg, and 1000 mg/kg has not yet been studied. The current studies were done by employing Swiss Albino mice as experimental animal. The methanolic extracts of Triphala were considered safe up to a dose of 1000 mg/kg when evaluated for acute oral toxicity in accordance with the OECD (Organization for Economic Cooperation and Development) guidelines. The results of acute toxicity showed no signs of toxicity such as general behaviour changes, mortality, changes on gross appearance or histopathological changes of the internal organs of rats. The examinations of signs of acute toxicity showed no abnormalities in the test groups as compared to the controls. Haematological and blood chemical values in treated groups were normal in comparison with the control group. Therefore, the extract of Triphala given orally to mice did not produce acute toxicities. The laxative activity on Albino Wistar rats shows that the Triphala extract has significant positive effect on constipated animals.

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Shrivastava, Ravi, Gareth W. John, Ginette Rispat, Annick Chevalier, and Roy Massingham. "Can the In Vivo Maximum Tolerated Dose be Predicted Using In Vitro Techniques? A Working Hypothesis." Alternatives to Laboratory Animals 19, no. 4 (1991): 393–402. http://dx.doi.org/10.1177/026119299101900403.

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All new chemical entities synthesised in our laboratories have routinely been subjected to in vitro toxicity tests. Out of curiosity, we established a working hypothesis in which the in vitro data could be empirically transformed to predict the in vivo four-week standard maximum tolerated dose (MTD) studies in rats and dogs. As a first step to verifying this hypothesis, we report here the findings of an in vitro cytotoxicity study of 25 compounds randomly selected from our files, possessing a wide range of pharmacological activities and for which data from standard four-week MTD studies were available. Single blind in vitro toxicity studies in three carefully selected types of primary and cell line cultures were carried out. In vitro CT50 (concentration inducing 50% cell death) and CT100 (concentration inducing 100% cell death) values were obtained for each of the three cell types and, using empirical assumptions, these results were used to predict the MTD in vivo in the rat and dog. The actual in vivo threshold and toxic doses were obtained from the MTD study reports. The in vivo toxicity values predicted from the in vitro toxicity results with this series of 25 compounds showed a better than 80% correlation with the actual in vivo results obtained in the MTD studies. Whether or not in vitro cytotoxicity predictions are ultimately found to be directly and consistently related to the MTD in vivo for all pharmacological classes of compounds will require many additional studies, but it is hoped that these results will stimulate the necessary research effort required to answer this question.

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Saberi-Hasanabadi, Parisa, Obeid M. Malekshah, and Hamidreza Mohammadi. "The Exposure and Hazards of Zinc Oxide Nanoparticles: In Vitro and In Vivo Studies." Pharmaceutical and Biomedical Research 9, no. 2 (2023): 77–84. http://dx.doi.org/10.32598/pbr.9.2.920.2.

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Background: Extensive application of zinc oxide nanoparticles has increased the likelihood of its release into the environment and subsequent human exposure and toxicity. The toxicity is thought to be a combined effect of intracellular particles and the release of dissolved zinc ions. Objectives: This review outlines the possible mechanisms of zinc oxide toxicity in biological organs through in vitro and in vivo experiments. Methods: We reviewed articles published between 2001 and 2021. In this way, we did a manual search of Google Scholar and scientific databases, including PubMed, Web of Science, Scopus, and Embase, with keywords such as “zinc oxide nanoparticles”, “toxicity mechanism”, and “in vivo and in vitro studies”. The other qualified papers contained the history of identifying zinc oxide nanoparticles, the toxicity of metallic nanoparticles, and physical, chemical, and biological side effects with topical and systematic approaches. Results: The main mechanism suggested for zinc-based nanoparticles-induced cell damage is via the induction of increased levels of reactive oxygen species, which are oxidative stress markers. This mechanism has also been found to be a key mechanism for the cytotoxicity of other metal nanomaterials. Zinc-based nanoparticles were found to induce oxidative DNA damage, inflammation, progressive degenerative cell changes, cell cycle arrest, cytogenetic alterations, and ROS-triggered mitochondria-mediated apoptosis in human organs. Conclusion: This review sheds light on the full understanding of in vitro and in vivo toxicity assessment of zinc oxide nanoparticles, highlighting the health concerns from the perspective of ZnO nanoparticles release to the ecosystem after their increasing application.

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Perdomo, Cintya, Elena Aguilera, Ileana Corvo, et al. "Preclinical Studies in Anti-Trypanosomatidae Drug Development." Pharmaceuticals 14, no. 7 (2021): 644. http://dx.doi.org/10.3390/ph14070644.

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The trypanosomatid parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania are the causative agents of human African trypanosomiasis, Chagas Disease and Leishmaniasis, respectively. These infections primarily affect poor, rural communities in the developing world, and are responsible for trapping sufferers and their families in a disease/poverty cycle. The development of new chemotherapies is a priority given that existing drug treatments are problematic. In our search for novel anti-trypanosomatid agents, we assess the growth-inhibitory properties of >450 compounds from in-house and/or “Pathogen Box” (PBox) libraries against L. infantum, L. amazonensis, L.braziliensis, T. cruzi and T. brucei and evaluate the toxicities of the most promising agents towards murine macrophages. Screens using the in-house series identified 17 structures with activity against and selective toward Leishmania: Compounds displayed 50% inhibitory concentrations between 0.09 and 25 μM and had selectivity index values >10. For the PBox library, ~20% of chemicals exhibited anti-parasitic properties including five structures whose activity against L. infantum had not been reported before. These five compounds displayed no toxicity towards murine macrophages over the range tested with three being active in an in vivo murine model of the cutaneous disease, with 100% survival of infected animals. Additionally, the oral combination of three of them in the in vivo Chagas disease murine model demonstrated full control of the parasitemia. Interestingly, phenotyping revealed that the reference strain responds differently to the five PBox-derived chemicals relative to parasites isolated from a dog. Together, our data identified one drug candidate that displays activity against Leishmania and other Trypanosomatidae in vitro and in vivo, while exhibiting low toxicity to cultured mammalian cells and low in vivo acute toxicity.

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Danzeisen, Ruth, David Lee Williams, Vanessa Viegas, Michael Dourson, Steven Verberckmoes, and Arne Burzlaff. "Bioelution, Bioavailability, and Toxicity of Cobalt Compounds Correlate." Toxicological Sciences 174, no. 2 (2020): 311–25. http://dx.doi.org/10.1093/toxsci/kfz249.

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Abstract Based on the wide use of cobalt substances in a range of important technologies, it has become important to predict the toxicological properties of new or lesser-studied substances as accurately as possible. We studied a group of 6 cobalt substances with inorganic ligands, which were tested for their bioaccessibility (surrogate measure of bioavailability) through in vitro bioelution in simulated gastric and intestinal fluids. Representatives of the group also underwent in vivo blood kinetics and mass balance tests, and both oral acute and repeated dose toxicity (RDT) testing. We were able to show a good correlation between high in vitro bioaccessibility with high in vivo bioavailability and subsequent high in vivo toxicity; consequently, low in vitro bioaccessibility correlated well with low in vivo bioavailability and low in vivo toxicity. In vitro bioelution in simulated gastric fluid was the most precise predictor of the difference in the oral RDT lowest observed adverse effect levels of 2 compounds representing the highly and poorly bioaccessible subset of substances. The 2 compounds cobalt dichloride hexahydrate and tricobalt tetraoxide differed by a factor of 440 in their in vitro bioaccessibility and by a factor of 310 in their RDT lowest observed adverse effect level. In summary, this set of studies shows that solubility, specifically in vitro bioelution in simulated gastric fluid, is a good, yet conservative, predictor of in vivo bioavailability and oral systemic toxicity of inorganic cobalt substances. Bioelution data are therefore an invaluable tool for grouping and read across of cobalt substances for hazard and risk assessment.

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Alencar, Marcus V. O. B., Muhammad T. Islam, Eunus S. Ali, et al. "Association of Phytol with Toxic and Cytotoxic Activities in an Antitumoral Perspective: A Meta-Analysis and Systemic Review." Anti-Cancer Agents in Medicinal Chemistry 18, no. 13 (2019): 1828–37. http://dx.doi.org/10.2174/1871520618666180821113830.

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Background: Phytol have various pharmacological activities such as antimicrobial, cytotoxic, antitumoral, antimutagenic, anti-atherogenic, antidiabetic, lipid-lowering, antispasmodic, antiepileptic, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant and immunoadjuvant. Several studies point to an association of phytol with implications for apoptosis and necrosis at cellular levels in cancer, yet no clear conclusions were drawn. Method: To clarify this, we conducted a meta-analysis of non-clinical studies of phytol and its associations with toxicity and cytotoxicity emphasizing the mechanisms of apoptosis and necrosis induction and its importance in tumor therapy. Relevant studies were systematically searched in PubMed and Web of Science. The association between phytol and cyto-/toxicity was assessed by odds ratio (ORs) and 95% confidence intervals (CI). Twentythree studies were finally included in the meta-analysis. A significant association between phytol and toxicity (OR: 1.47; 95% CI = 0.86–2.48) was found among in vivo studies and cytotoxicity (OR: 1.81; 95% CI = 1.12– 2.65, p<0.05) in in vitro and ex vivo studies. In in vitro studies, 24% of them indicate that phytol at high doses induces apoptosis by several mechanisms; while about 40% of ex vivo studies indicate that phytol induces reactive oxygen species generation. But, Phytol does not act as a direct oxidant, unlike its metabolite phytanic acid. The 24% of in vivo studies also highlighted the mechanisms for apoptosis-like including expression of Bcl2 protein or mutations in pro-apoptotic protein Bax. Of them, 8% studies show necrosis and hepatotoxicity. However, in 24% of the articles, the mechanisms of toxicity and cytotoxicity are still not well elucidated. Conclusion: This study confirms that the association between phytol and cyto-/toxicity depends on the dose/concentration used in the given experimental conditions. Thus, there are still great prospects for new research aimed at the use of phytol and its metabolite as anticancer agents.

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Chadha, Renu, Swati Bhandari, Jamshed Haneef, Sadhika Khullar, and Sanjay Mandal. "Cocrystals of telmisartan: characterization, structure elucidation, in vivo and toxicity studies." CrystEngComm 16, no. 36 (2014): 8375–89. http://dx.doi.org/10.1039/c4ce00797b.

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Tasker, R. A. R., B. J. Connell, and S. M. Strain. "Pharmacological, behavioural and morphological studies of domoic acid toxicity in vivo." European Journal of Pharmacology 183, no. 3 (1990): 959. http://dx.doi.org/10.1016/0014-2999(90)92800-x.

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Liu, Ai Hong. "In Vivo Studies of the Toxicity of Multi-Wall Carbon Nanotubes." Advanced Materials Research 345 (September 2011): 287–91. http://dx.doi.org/10.4028/www.scientific.net/amr.345.287.

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Carbon nanotubes (CNTs) may play a significant role in the biomedical field in future. Therefore, it is imperative to thoroughly investigate the toxicity and the biocompatibility of CNTs. However, the data about the toxicity of carbon nanotubes in vivo is poor or contradictory. In this study, rats were instilled with different dose mutil-wall carbon nanotubes (MWCNTs) by intravenous injection and euthanized 90d after the single treatment for histopathological study of the lungs and other organs. All rats survived within our experimental period and no large changes in their weights appeared. It is confirmed that all MWCNTs-exposed rats suffered multiple lesions. Obvious changes of the structure of lung tissue and the micrograph of MWCNTs in lung tissue were observed by TEM, while other tissues were in order. The results suggest that MWCNTs can induce lung toxicity in the expose modes of intravenous injection.

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Braga, Teresa M., Lídia Rocha, Tsz Yan Chung, et al. "Azadirachta indica A. Juss. In Vivo Toxicity—An Updated Review." Molecules 26, no. 2 (2021): 252. http://dx.doi.org/10.3390/molecules26020252.

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The Neem tree, Azadirachta indica A. Juss., is known for its large spectrum of compounds with biological and pharmacological interest. These include, among others, activities that are anticancer, antibacterial, antiviral, and anti-inflammatory. Some neem compounds are also used as insecticides, herbicides, and/or antifeedants. The safety of these compounds is not always taken into consideration and few in vivo toxicity studies have been performed. The current study is a literature review of the latest in vivo toxicity of A. indica. It is divided in two major sections—aquatic animals toxicity and mammalian toxicity—each related to neem’s application as a pesticide or a potential new therapeutic drug, respectively.

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Yah, Clarence S., and Geoffrey S. Simate. "Engineered nanoparticle bio-conjugates toxicity screening: The xCELLigence cells viability impact." BioImpacts 10, no. 3 (2020): 195–203. http://dx.doi.org/10.34172/bi.2020.24.

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Introduction: The vast diverse products and applications of engineered nanoparticle bio-conjugates (ENPBCs) are increasing, and thus flooding the-markets. However, the data to support risk estimates of ENPBC are limited. While it is important to assess the potential benefits, acceptability and uptake, it is equally important to understand where ENPBCs safety is and how to expand and affirm consumer security concerns. Methods: Online articles were extracted from 2013 to 2016 that pragmatically used xCELLigence real-time cell analysis (RTCA) technology to describe the in-vitro toxicity of ENPBCs. The xCELLigence is a +noninvasive in vitro toxicity monitoring process that mimics exact continuous cellular bio-responses in real-time settings. On the other hand, articles were also extracted from 2008 to 2016 describing the in vivo animal models toxicity of ENPBCs with regards to safety outcomes. Results: Out of 32 of the 121 (26.4%) articles identified from the literature, 23 (71.9%) met the in-vitro xCELLigence and 9(28.1%) complied with the in vivo animal model toxicity inclusion criteria. Of the 23 articles, 4 of them (17.4%) had no size estimation of ENPBCs. The xCELLigence technology provided information on cell interactions, viability, and proliferation process. Eighty-three (19/23) of the in vitro xCELLigence technology studies described ENPBCs as nontoxic or partially nontoxic materials. The in vivo animal model provided further toxicity information where 1(1/9) of the in vivo animal model studies indicated potential animal toxicity while the remaining results recommended ENPPCs as potential candidates for drug therapy though with limited information on toxicity. Conclusion: The results showed that the bioimpacts of ENPBCs either at the in vitro or at in vivo animal model levels are still limited due to insufficient information and data. To keep pace with ENPBCs biomedical products and applications, in vitro, in vivo assays, clinical trials and long-term impacts are needed to validate their usability and uptake. Besides, more real-time ENPBCs-cell impact analyses using xCELLigence are needed to provide significant data and information for further in vivo testing.

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Ali, Harzhin Hiwa, and Tavga Ahmed Aziz. "Renal Toxicity of Tenofovir: Narrative Review." Al-Rafidain Journal of Medical Sciences ( ISSN: 2789-3219 ) 2 (April 9, 2022): 40–50. http://dx.doi.org/10.54133/ajms.v2i.63.

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Tenofovir is a reverse-transcriptase inhibitor based on acyclic nucleotide analogs. Tenofovir is a drug that is often used in treating HIV infection and has also been approved for treating infection by the hepatitis B virus. Despite the fact that its renal safety has been demonstrated in cell culture and clinical trials, clinical use and in vivo animal studies have shown its association with a low, but important, risk of kidney injury. Tenofovir accumulation in these mitochondria-rich cells is explained by proximal tubular cell secretion. Proximal tubular cell dysfunction is a symptom of Tenofovir nephrotoxicity, which might be the leading cause of acute renal injury or chronic diseases of the kidney. A review of articles is performed using keywords related to the topic in the databases of Google Scholar and PubMed, and 54 papers have been included, which were case studies, cross-sectional studies, and in vivo animal studies from 2004 up to 2021. The review aims at explaining the interaction of Tenofovir with kidney tubules, an association of genetic polymorphism, clinical features of Tenofovir-induced renal toxicity, potential mechanisms of Tenofovir-induced renal toxicity, its predisposing conditions and factors, and finally, some proposed strategies and agents to monitor and manage Tenofovir-induced nephrotoxicity.

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Yogev, Sivan, Ayelet Shabtay-Orbach, Abraham Nyska, and Boaz Mizrahi. "Local Toxicity of Topically Administrated Thermoresponsive Systems: In Vitro Studies with In Vivo Correlation." Toxicologic Pathology 47, no. 3 (2018): 426–32. http://dx.doi.org/10.1177/0192623318810199.

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Thermoresponsive materials have the ability to respond to a small change in temperature—a property that makes them useful in a wide range of applications and medical devices. Although very promising, there is only little conclusive data about the cytotoxicity and tissue toxicity of these materials. This work studied the biocompatibility of three Food and Drug Administration approved thermoresponsive polymers: poly( N-isopropyl acrylamide), poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer, and poly(lactic acid-co-glycolic acid) and poly(ethylene glycol) tri-block copolymer. Fibroblast NIH 3T3 and HaCaT keratinocyte cells were used for the cytotoxicity testing and a mouse model for the in vivo evaluation. In vivo results generally showed similar trends as the results seen in vitro, with all tested materials presenting a satisfactory biocompatibility in vivo. pNIPAM, however, showed the highest toxicity both in vitro and in vivo, which was explained by the release of harmful monomers and impurities. More data focusing on the biocompatibility of novel thermoresponsive biomaterials will facilitate the use of existing and future medical devices.

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Toukourou, Habib, Francine Uwambayinema, Yousof Yakoub, et al. "In Vitro and In Vivo Toxicity Studies on Cymbopogon giganteus Chiov. Leaves Essential Oil from Benin." Journal of Toxicology 2020 (January 28, 2020): 1–12. http://dx.doi.org/10.1155/2020/8261058.

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Cymbopogon giganteus Chiov. (Poaceae) is a medicinal plant used to treat various diseases in traditional medicine in several African countries. The present study aims to evaluate the oral and inhalation toxicity as well as the mutagenic effects of the essential oil of Cymbopogon giganteus leaves (EOCG) from a sample collected in Benin. Mutagenic potential was assessed by the Ames test using Salmonella typhimurium strains TA98 and TA100. Oral acute toxicity was carried out by administration of a single dose of 2000 mg/kg b.w. to Wistar rats while oral subacute toxicity was assessed by daily administration of 50 and 500 mg/kg of EOCG for 28 days. Finally, inhalation toxicity was assessed by administration of a single dose of 0.125%, 0.5%, 2% or 5% v/v of EOCG emulsions in 0.05% v/v lecithin solution in sterile water for the first experiment, and in a second one by administration of single dose of 0.125% or 0.5% v/v. A broncho-alveolar lavage was performed after 3 h or 24 h, respectively. The results show that EOCG is not mutagenic on Salmonella typhimurium strains at the highest concentration tested (200 μg/plate). In the acute oral toxicity study, EOCG induce neither mortality nor toxicity, showing that the LD50 is greater than 2000 mg/kg. The subacute oral toxicity study at both doses did not show any significant difference in body weight, relative organ weight, hematological and/or biochemical parameters or histopathology as compared to the control group. EOCG induced mortality and inflammation in lungs 3 h after administration of a single dose of 5% or 2% v/v. Single doses of 0.125% or 0.5% v/v did not induce inflammation, cell recruitment nor cytotoxicity in lungs 3 h or 24 h after administration, suggesting safety at these concentrations. This first report on the in vivo toxicity will be useful to guide safe uses of EOCG.

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Karabay, Ülkü. "NONCLINICAL SAFETY ASSESSMENT OF VACCINES: UP TO DATE APPLICATIONS." Ege Tıp Dergisi 63, no. 4 (2024): 644–59. https://doi.org/10.19161/etd.1542896.

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Vaccines have a great impact on global health. These pharmaceutical products are prophylactic agents administered to healthy individuals, involving infants and children. Therefore, it is important to demonstrate the safety of them with nonclinical studies before the start of clinical trials. Nonclinical assessment includes product characterization, both in vitro and in vivo testing of vaccines, adjuvanted vaccines or vaccine adjuvants. In vivo safety studies contain pharmacology studies, pharmacokinetic studies, general toxicity studies, developmental and reproductive toxicity, genotoxicity and carcinogenicity studies, and immunogenicity assessment. These tests should be conducted in compliance with GLPs. Nonclinical studies are conducted to determine the safety and appropriate dose to induce an immune response in animal models. A benefit-to-risk profile is considered for each vaccine because of many factors that affect nonclinical and clinical toxicities. Herewith, the non-clinical safety evaluation of vaccines, including toxicity testing, has been focused. Nonclinical testing requirements are an essential tool to determination of the safety and efficacy of vaccines.

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Stan, Roxana Liana, Bogdan Sevastre, Adriana Corina Hangan, et al. "Chemical Characterization of Artemisia Annua L. Extract Assessment of Antioxidant Activity in vitro and in vivo Toxicity Studies." Revista de Chimie 70, no. 6 (2019): 1903–7. http://dx.doi.org/10.37358/rc.19.6.7243.

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The purpose of the study was to demonstrate in vitro antioxidant activity and in vivo toxicity of the Artemisia Annua L. extract. The plant was harvested from Bihor area (Crisul Repede and Negru river valleys), Romania. Preparation of the plant product and of the lyophilizated extract was carried out in accordance with the Romanian Pharmacopeia Xth Edition. Lyophilized extract was evaluated in terms of polyphenol content using HPLC method. Antioxidant activity was highlighted using the DPPH, ABTS and FRAP methods. Hepatic, renal and haematological toxicity studies have been performed on laboratory mice. For this purpose blood and organs were collected. Biochemical and haematological parameters were determined on the blood samples and histopathological examination was performed on organs. In vitro antioxidant effect of Artemisia Annua L extract and its lack of in vivo toxicity were demonstrated. It is desirable to obtain a new phytoproduct harvested from spontaneous flora of Romania with antioxidant / antitumoral properties and which is devoid of toxicity.

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Arjmand, Farukh, Imtiyaz Yousuf, Yusra Zaidi, and Loic Toupet. "Crystal structure determination, spectroscopic characterization and biological profile of a tailored ionic molecular entity, Sn(iv) iminodiacetic acid–piperazinediium conjugate: in vitro DNA/RNA binding studies, Topo I inhibition activity, cytotoxic and systemic toxicity studies." RSC Advances 5, no. 21 (2015): 16250–64. http://dx.doi.org/10.1039/c4ra13718c.

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Sijko, Monika, and Lucyna Kozłowska. "Influence of Dietary Compounds on Arsenic Metabolism and Toxicity. Part I—Animal Model Studies." Toxics 9, no. 10 (2021): 258. http://dx.doi.org/10.3390/toxics9100258.

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Population and laboratory studies indicate that exposure to various forms of arsenic (As) is associated with many adverse health effects; therefore, methods are being sought out to reduce them. Numerous studies focus on the effects of nutrients on inorganic As (iAs) metabolism and toxicity, mainly in animal models. Therefore, the aim of this review was to analyze the influence of methionine, betaine, choline, folic acid, vitamin B2, B6, B12 and zinc on the efficiency of iAs metabolism and the reduction of the severity of the whole spectrum of disorders related to iAs exposure. In this review, which includes 58 (in vivo and in vitro studies) original papers, we present the current knowledge in the area. In vitro and in vivo animal studies showed that methionine, choline, folic acid, vitamin B2, B12 and zinc reduced the adverse effects of exposure to iAs in the gastrointestinal, urinary, lymphatic, circulatory, nervous, and reproductive systems. On the other hand, it was observed that these compounds (methionine, choline, folic acid, vitamin B2, B12 and zinc) may increase iAs metabolism and reduce toxicity, whereas their deficiency or excess may impair iAs metabolism and increase iAs toxicity. Promising results of in vivo and in vitro on animal model studies show the possibility of using these nutrients in populations particularly exposed to As.

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Zhang, Yongbin, Wei Chen, Jun Zhang, Jing Liu, Guangping Chen, and Carey Pope. "In Vitro and In Vivo Toxicity of CdTe Nanoparticles." Journal of Nanoscience and Nanotechnology 7, no. 2 (2007): 497–503. http://dx.doi.org/10.1166/jnn.2007.125.

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Cadmium telluride (CdTe) nanoparticles exhibit strong and stable fluorescence that is attractive for many applications such as biological probing and solid state lighting. The evaluation of nanoparticle toxicity is important for realizing these practical applications. However, no systematic studies of CdTe nanoparticle toxicity have been reported. We investigated and compared the size- and concentration-dependent cytotoxicity of CdTe nanoparticles in human hepatoma HepG2 cells using the MTT assay. CdTe nanoparticles elicited cytotoxicity in a concentration- and size-dependent manner, with smaller-sized particles exhibiting somewhat higher potency. Lesser cytotoxicity of partially purified CdTe-Red particles (following methanol precipitation and resuspension) suggested that free cadmium ions may contribute to cytotoxicity. We also evaluated the acute toxicity of CdTe-Red particles following intravenous exposure in male rats (2 μmol/kg). Few signs of functional toxicity or clinical (urinary or blood) changes were noted. Interestingly, motor activity was transiently reduced (2 hours after treatment) and then significantly increased at a later timepoint (24 hours after dosing). These studies provide a framework for further characterizing the in vitro and in vivo toxic potential of different types of CdTe nanoparticles and suggest that the nervous system may be targeted by these nanoparticles under some conditions.

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Magklaras, Alexandros-Dimitrios C., Christina N. Banti, and Sotiris K. Hadjikakou. "Antiproliferative Activity of Antibiotics through DNA Binding Mechanism: Evaluation and Molecular Docking Studies." International Journal of Molecular Sciences 24, no. 3 (2023): 2563. http://dx.doi.org/10.3390/ijms24032563.

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The antiproliferative activity of three antibiotics clinically use, was studied through DNA inhibition mechanisms, ex vivo, in silico and in vitro. The ex vivo interaction of DNA with ciprofloxacin hydrochloride (CIP·HCl), penicillin G sodium salt (PEN·Na), and tetracycline hydrochloride (TC·HCl) was determined by UV-Vis spectra and viscosity measurements. Furthermore, their binding constants (Kb) toward CT-DNA were calculated (Kb = (2.8 ± 0.6) × 104 (CIP·HCl), (0.4 ± 0.1) × 104 (PEN·Na) and (6.9 ± 0.3) × 104 (TC·HCl) Μ−1). Docking studies on the binding interactions of antibiotics with DNA were performed to rationalize the ex vivo results. The in vitro antiproliferative activity of the antibiotics was evaluated against human breast adenocarcinoma (MCF-7) cells (IC50 values: 417.4 ± 28.2 (CIP·HCl), >2000 (PEN·Na) and 443.1 ± 17.2 (TC·HCl) μΜ). Cell cycle arrest studies confirmed the apoptotic type of MCF-7 cells. The toxicity of the studied agents was in vitro tested against human fetal lung fibroblast cells (MRC-5). The results are compared with the corresponding one for doxorubicin (DOX). Despite their low binding affinity to DNA (Kb) or their different mode of interaction, TC·HCl (anthracycline) or CIP·HCl (quinolones), exhibit notable antiproliferative activity and low toxicity.

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Hawksworth, Gabrielle M. "Advantages and Disadvantages of Using Human Cells for Pharmacological and Toxicological Studies." Human & Experimental Toxicology 13, no. 8 (1994): 568–73. http://dx.doi.org/10.1177/096032719401300811.

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1 Marked species differences in the distribution and affinity of drug receptors, and in the patterns of biotransformation and susceptibility to the toxicity of xenobiotics, provide the impetus for using human tissues for pharmacological and toxicological studies. 2 Studies with intact cells facilitate the correlation of xenobiotic metabolism with cellular indices of toxicity, which can provide the mechanistic basis for understanding species differences in toxicity. 3 Human cells in suspension or primary culture reflect the variability in susceptibility to toxicity in a population. 4 The current limitation to these studies is scarcity of human material, the need for improved (cryo)preservation techniques for human hepatocytes/precision-cut slices and difficulties in predicting in vivo exposure-risk relationships from in vitro dose-response relationships.

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Harčárová, M., E. Čonková, M. Proškovcová, and M. Falis. "In Vivo Assessment of Zearalenone Toxicity." Folia Veterinaria 64, no. 2 (2020): 60–65. http://dx.doi.org/10.2478/fv-2020-0018.

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AbstractThe microscopic filamentous fungi of the genus Fusarium are capable of producing secondary metabolites—mycotoxins. Fusarium fungi synthesize trichothecenes, zearalenone (ZEA) and fumonisins under appropriate environmental conditions. In this biological experiment, we studied the effects of zearalenone on a model organism called Artemia franciscana. During the three-day in vivo tests, we used five different concentrations of zearalenone (0.08 ppm, 0.4 ppm, 2 ppm, 10 ppm and 50 ppm). The results of this study showed that as the zearalenone concentration and the duration of the mycotoxin exposure increased, the lethality of artemia also increased. Our study showed that the toxicity of zearalenone to Artemia franciscana was relatively low.

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Nikam, Ajinkya N., Abhijeet Pandey, Shivanand H. Nannuri, et al. "Hyaluronic Acid-Protein Conjugate Modified Iron-Based MOFs (MIL-101 (Fe)) for Efficient Therapy of Neuroblastoma: Molecular Simulation, Stability and Toxicity Studies." Crystals 12, no. 10 (2022): 1484. http://dx.doi.org/10.3390/cryst12101484.

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Iron-based metal-organic frameworks (MIL (101)) have recently gained attention in materials science for biomedical applications. In the present work, Iron-based MOF (MIL-101(Fe)) were coated with lactoferrin (Lf) conjugated with hyaluronic acid (HA) and investigated its potential for delivering 5-fluorouracil (5-FU), along with assessing the toxicity profile. The synthesised nanoparticles were extensively characterised using spectroscopic, X-Ray, thermal and electron microscopic techniques. 5-FU was loaded into MOFs, and the drug-loading efficiency and drug release pattern were studied, along with stability testing in pH and serum protein. The toxicity of MIL-101(Fe) was assessed using both in vitro and in vivo techniques such as the haemolysis assay, cell viability assay and acute and subacute toxicity studies in animals. In silico molecular simulation was done to assess the Lf and Tf interaction. The molecular interaction of Lf with Transferrin (Tf) showed strong molecular interaction and negligible fluctuation in the RMSD (root mean square deviation) values. The MOFs were stable and demonstrated sustained drug release patterns. The in vitro cell studies demonstrated biocompatibility and enhanced cellular internalisation of MOFs. The in vivo toxicity studies supported the in vitro results. The synthesised MOFs demonstrated potential as a targeted delivery platform for cancer targeting.

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Khaira, Gurpreet Kaur, Abhijit Ganguli, and Moushumi Ghosh. "Antimicrobial efficacy and in vivo toxicity studies of a quaternized biopolymeric flocculant." Journal of Water and Health 12, no. 4 (2014): 656–62. http://dx.doi.org/10.2166/wh.2014.186.

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This study evaluated the antibacterial spectrum and safety of a chemically modified biopolymeric flocculant (TMB) against waterborne pathogens. The biopolymer previously characterized as polysaccharide with flocculating activity is produced extracellularly by the bacterium Klebsiella terrigena. The amino sugars on the polymer were chemically modified by quaternization, which resulted in N,N,N trimethyl biopolymer (TMB). Quaternization was effective in imparting biocidal activity to TMB against five selected waterborne pathogens, namely, Aeromonas hydrophila, Yersinia enterocolitica, Salmonella typhimurium, Listeria monocytogenes and Escherichia coli O157:H7. 99.999% inactivation was achieved with S. typhimurium at a dose of 60 μg ml−1 of TMB within 60 min at the ambient temperature, followed by other pathogens. Haemotological, histopathological and general examinations indicated no adverse effects in Swiss albino mice fed with the quaternized biopolymer (120 mg kg−1 body weight−1 day−1) over a period of 30 days. These results suggested that TMB was tolerated well without any signs of toxicity and may have potential application as a safe, antimicrobial bioflocculant for both removing and inactivating waterborne pathogens.

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Lopez-Chaves, Carlos, Juan Soto-Alvaredo, Maria Montes-Bayon, Jörg Bettmer, Juan Llopis, and Cristina Sanchez-Gonzalez. "Gold nanoparticles: Distribution, bioaccumulation and toxicity. In vitro and in vivo studies." Nanomedicine: Nanotechnology, Biology and Medicine 14, no. 1 (2018): 1–12. http://dx.doi.org/10.1016/j.nano.2017.08.011.

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Cyrillo Guimarães da Silva, Juliana, Cassiana Bigolin, Laura Cé da Silva, et al. "Neurotoxicity evaluation of meloxicam in the alternative in vivo model, Caenorhabditis elegans." International Journal for Innovation Education and Research 8, no. 8 (2020): 319–25. http://dx.doi.org/10.31686/ijier.vol8.iss8.2522.

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Inflammatory processes cause changes in the permeability of the blood brain barrier. Non-steroidal anti-inflammatory drugs (NSAID) are most commonly used to treat these inflammatory processes, including meloxicam, and they can reach the central nervous system (CNS) and cause neurotoxicity. Since there are no studies evaluating the neurotoxicity of NSAID in alternative models of toxicity, the aim of this study was to evaluate the acute neurotoxicity (through nematodes changes in behavior) of meloxicam in an alternative in vivo model, Caenorhabditis elegans, as well as, to determine meloxicam toxicity through LD50 and development assessments. Meloxicam LD50 was high (50.03 mg/mL) and only the highest dose (100 mg/mL) caused a decrease in the nematode body size, indicating low toxicity in this alternative model. Besides, a neurological effect was observed only in the highest dose. Meloxicam showed neurotoxicity only at a very high dose, suggesting low potential to cause toxicity in the CNS. However, further studies are necessary to evaluate meloxicam neurotoxicity.

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Moore, Brenda D., Jason Martin, Lorena de Mena та ін. "Short Aβ peptides attenuate Aβ42 toxicity in vivo". Journal of Experimental Medicine 215, № 1 (2017): 283–301. http://dx.doi.org/10.1084/jem.20170600.

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Processing of amyloid-β (Aβ) precursor protein (APP) by γ-secretase produces multiple species of Aβ: Aβ40, short Aβ peptides (Aβ37–39), and longer Aβ peptides (Aβ42–43). γ-Secretase modulators, a class of Alzheimer’s disease therapeutics, reduce production of the pathogenic Aβ42 but increase the relative abundance of short Aβ peptides. To evaluate the pathological relevance of these peptides, we expressed Aβ36–40 and Aβ42–43 in Drosophila melanogaster to evaluate inherent toxicity and potential modulatory effects on Aβ42 toxicity. In contrast to Aβ42, the short Aβ peptides were not toxic and, when coexpressed with Aβ42, were protective in a dose-dependent fashion. In parallel, we explored the effects of recombinant adeno-associated virus–mediated expression of Aβ38 and Aβ40 in mice. When expressed in nontransgenic mice at levels sufficient to drive Aβ42 deposition, Aβ38 and Aβ40 did not deposit or cause behavioral alterations. These studies indicate that treatments that lower Aβ42 by raising the levels of short Aβ peptides could attenuate the toxic effects of Aβ42.

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Mariya, Alfin, Aparna P., Adheena Xavier, et al. "Evaluation of Acute Toxicity of Scopolamine in Daphnia magna: An In silico and In vivo Approach." Asian Journal of Current Research 10, no. 2 (2025): 257–63. https://doi.org/10.56557/ajocr/2025/v10i29372.

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Scopolamine is a toxic but pharmacologically significant alkaloid presents in many plants of the Solanaceae family. In the present study, In silico and In vivo assessment of acute toxicity of scopolamine was done in Daphnia magna. In silico evaluation of toxicity was done using the QSAR Modeling software, TEST and predicted the acute LC50 in Daphnia magna. The in vivo study used 10 D. magna adults. D. magna was treated with various concentrations (1, 5 10, 50, 100, 200 and 500 µg/ml) of scopolamine for 24 hours. After exposure, the number of live mobile and dead daphnids was recorded. The In silico toxicity studies showed LC50 of 4.57µg/mL against D. magna, and the In vivo LC50 was found to be 6.591µg/mL. The present study concluded that scopolamine possessed significant ecotoxic potential indicated by the in silico and In vivo results.

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Wang, Yuanyuan, Li Li, Yanling Mu, et al. "Acute, subchronic toxicity and genotoxicity studies of JointAlive, a traditional Chinese medicine formulation for knee osteoarthritis." PLOS ONE 18, no. 10 (2023): e0292937. http://dx.doi.org/10.1371/journal.pone.0292937.

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Aim In vivo and in vitro toxicity tests of JointAlive® were studied in animal models to support the safe use of JointAlive® as a drug for knee osteoarthritis treatment. Methods The acute toxicity study in Sprague Dawley (SD) rats was conducted at a 20 g/kg bw/day dose of JointAlive®. For 13-week subchronic toxicity tests, SD rats were orally dosed daily with 0.5, 1.5 and 5 g/kg bw/day of JointAlive®. To assess the potential genotoxicity, Ames test, cellular chromosome aberration and mouse micronucleus test in vivo were carried out. Results Based on a lack of notable findings other than histopathology finding of co-incidental prostate inflammation at the high dose, the “No Observed Adverse Effect Level (NOAEL)” of JointAlive® was concluded as 5 g/kg bw/day in males and females. Results also indicated that JointAlive® has no risk of genotoxicity. Conclusions General toxicity and genotoxicity studies empirically demonstrated that JointAlive® poses a low risk of potential health risks, providing safety supports for the application of JointAlive® as a potential drug candidate to treat knee osteoarthritis.

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Levshukova, P. O., D. A. Kolesnik, E. V. Kuvaeva, E. N. Kirillova, and D. Y. Ivkin. "Approach to synthesis and study of pharmacological effects of new 1,3,5-triazine derivatives." Farmaciya 73, no. 1 (2024): 52–56. http://dx.doi.org/10.29296/25419218-2024-01-07.

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Introduction. Among the derivatives of 1,3,5-triazine, compounds with different biological activity are known, but there are few drugs of this structure on the pharmaceutical market. Thus, the production of new medicines based on a triazine core, as well as the study of their biological activity is an urgent direction. Objective: synthesis of new 1,3,5-triazine derivatives using the reaction of recycling of 2,5-disubstituted-4-hydroxy-6H-1,3-oxazine-6-ones by 1,3-binucleophiles to obtain different substituents at positions 2,4,6 in one stage, as well as assessment of acute toxicity, diuretic activity in silico and in vivo for synthesized products. Material and methods. The target compounds were obtained as a result of the interaction of 2,5-disubstituted-4-hydroxy-6H-1,3-oxazine-6-ones and S-methylisothiourea of hemisulfate in the presence of an equimolar amount of sodium methylate in a methanol medium. Prediction of acute toxicity of the studied compound was carried out using the local version of the GUSAR software. Computer screening of biological activity was carried out using the PASS program. Acute toxicity in vivo was determined on white male mice. For experimental evaluation of the diuretic activity of the obtained compounds in vivo, the Taylor, Topliss model was included in the work. Results. 2-(methylsulfanyl)-4-(4-nitrophenyl)-6-ethyl-1,3,5-triazine, 2-(methylsulfanyl)-4-(4-nitrophenyl)-6-(pentane-1-yl)-1,3,5-triazine were obtained with a yield of 72% and 69%, respectively. The structure of the obtained compounds was proved using 1H and 13C NMR spectroscopy. The predicted and experimental data of acute toxicity correlate with each other, and the studied compounds belong to the class "low-toxic". During the screening of biological activity using the PASS program, data on the estimated diuretic activity were obtained. Studies of biological activity in vivo have shown that the target compounds have pronounced diuretic activity. Conclusion. New compounds have been synthesized, their structure has been proved using modern physico-chemical analysis methods. The results of computer prediction made it possible to determine the potential class of toxicity and identify potential biological activity. With the help of experimental pharmacological studies, it has been proved that the studied compounds have low toxicity and exhibit pronounced diuretic activity.

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Bent, Grace-Anne, Paul Maragh, Tara Dasgupta, Richard A. Fairman, and Lebert Grierson. "Kinetic and density functional theory (DFT) studies of in vitro reactions of acrylamide with the thiols: captopril, l-cysteine, and glutathione." Toxicology Research 4, no. 1 (2015): 121–31. http://dx.doi.org/10.1039/c4tx00070f.

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Patel, Ilabahen, Jeremiah Woodcock, Ryan Beams, et al. "Fluorescently Labeled Cellulose Nanofibers for Environmental Health and Safety Studies." Nanomaterials 11, no. 4 (2021): 1015. http://dx.doi.org/10.3390/nano11041015.

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An optimal methodology for locating and tracking cellulose nanofibers (CNFs) in vitro and in vivo is crucial to evaluate the environmental health and safety properties of these nanomaterials. Here, we report the use of a new boron-dipyrromethene (BODIPY) reactive fluorescent probe, meso-DichlorotriazineEthyl BODIPY (mDTEB), tailor-made for labeling CNFs used in simulated or in vivo ingestion exposure studies. Time-correlated single photon counting (TCSPC) fluorescence lifetime imaging microscopy (FLIM) was used to confirm covalent attachment and purity of mDTEB-labeled CNFs. The photoluminescence properties of mDTEB-labeled CNFs, characterized using fluorescence spectroscopy, include excellent stability over a wide pH range (pH2 to pH10) and high quantum yield, which provides detection at low (μM) concentrations. FLIM analysis also showed that lignin-like impurities present on the CNF reduce the fluorescence of the mDTEB-labeled CNF, via quenching. Therefore, the chemical composition and the methods of CNF production affect subsequent studies. An in vitro triculture, small intestinal, epithelial model was used to assess the toxicity of ingested mDTEB-labeled CNFs. Zebrafish (Danio rerio) were used to assess in vivo environmental toxicity studies. No cytotoxicity was observed for CNFs, or mDTEB-labeled CNFs, either in the triculture cells or in the zebrafish embryos.

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Zavala, Jose, Anastasia N. Freedman, John T. Szilagyi, et al. "New Approach Methods to Evaluate Health Risks of Air Pollutants: Critical Design Considerations for In Vitro Exposure Testing." International Journal of Environmental Research and Public Health 17, no. 6 (2020): 2124. http://dx.doi.org/10.3390/ijerph17062124.

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Air pollution consists of highly variable and complex mixtures recognized as major contributors to morbidity and mortality worldwide. The vast number of chemicals, coupled with limitations surrounding epidemiological and animal studies, has necessitated the development of new approach methods (NAMs) to evaluate air pollution toxicity. These alternative approaches include in vitro (cell-based) models, wherein toxicity of test atmospheres can be evaluated with increased efficiency compared to in vivo studies. In vitro exposure systems have recently been developed with the goal of evaluating air pollutant-induced toxicity; though the specific design parameters implemented in these NAMs-based studies remain in flux. This review aims to outline important design parameters to consider when using in vitro methods to evaluate air pollutant toxicity, with the goal of providing increased accuracy, reproducibility, and effectiveness when incorporating in vitro data into human health evaluations. This review is unique in that experimental considerations and lessons learned are provided, as gathered from first-hand experience developing and testing in vitro models coupled to exposure systems. Reviewed design aspects include cell models, cell exposure conditions, exposure chambers, and toxicity endpoints. Strategies are also discussed to incorporate in vitro findings into the context of in vivo toxicity and overall risk assessment.

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Haddoub, Carol, Mohamad Rima, Sandrine Heurtebise, et al. "Cytotoxic effect of Montivipera bornmuelleri’s venom on cancer cell lines: in vitro and in vivo studies." PeerJ 8 (October 27, 2020): e9909. http://dx.doi.org/10.7717/peerj.9909.

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Background Montivipera bornmuelleri’s venom has shown immunomodulation of cytokines release in mice and selective cytotoxicity on cancer cells in a dose-dependent manner, highlighting an anticancer potential. Here, we extend these findings by elucidating the sensitivity of murine B16 skin melanoma and 3-MCA-induced murine fibrosarcoma cell lines to M. bornmuelleri’s venom and its effect on tumor growth in vivo. Methods The toxicity of the venom on B16 and MCA cells was assessed using flow cytometry and xCELLigence assays. For in vivo testing, tumor growth was followed in mice after intratumoral venom injection. Results The venom toxicity showed a dose-dependent cell death on both B16 and MCA cells. Interestingly, overexpression of ovalbumin increased the sensitivity of the cells to the venom. However, the venom was not able to eradicate induced-tumor growth when injected at 100 µg/kg. Our study demonstrates a cytotoxic effect of M. bornmuelleri’s venom in vitro which, however, does not translate to an anticancer action in vivo.

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Gad, Shayne C., Kelly L. Sharp, Charles Montgomery, J. Donald Payne, and Glenn P. Goodrich. "Evaluation of the Toxicity of Intravenous Delivery of Auroshell Particles (Gold–Silica Nanoshells)." International Journal of Toxicology 31, no. 6 (2012): 584–94. http://dx.doi.org/10.1177/1091581812465969.

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Gold nanoshells (155 nm in diameter with a coating of polyethylene glycol 5000) were evaluated for preclinical biocompatibility, toxicity, and biodistribution as part of a program to develop an injectable device for use in the photothermal ablation of tumors. The evaluation started with a complete good laboratory practice (GLP) compliant International Organization for Standardization (ISO)-10993 biocompatibility program, including cytotoxicity, pyrogenicity (US Pharmacopeia [USP] method in the rabbit), genotoxicity (bacterial mutagenicity, chromosomal aberration assay in Chinese hamster ovary cells, and in vivo mouse micronucleus), in vitro hemolysis, intracutaneous reactivity in the rabbit, sensitization (in the guinea pig maximization assay), and USP/ISO acute systemic toxicity in the mouse. There was no indication of toxicity in any of the studies. Subsequently, nanoshells were evaluated in vivo by intravenous (iv) infusion using a trehalose/water solution in a series of studies in mice, Sprague-Dawley rats, and Beagle dogs to assess toxicity for time durations of up to 404 days. Over the course of 14 GLP studies, the gold nanoshells were well tolerated and, when injected iv, no toxicities or bioincompatibilities were identified.

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DeLoid, Glen M., Xiaoqiong Cao, Ramon M. Molina, et al. "Toxicological effects of ingested nanocellulose in in vitro intestinal epithelium and in vivo rat models." Environmental Science: Nano 6, no. 7 (2019): 2105–15. http://dx.doi.org/10.1039/c9en00184k.

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Shakola, Tatsiana V., Vasili V. Rubanik, Vasili V. Rubanik, et al. "Benzothiazole Derivatives of Chitosan and Their Derived Nanoparticles: Synthesis and In Vitro and In Vivo Antibacterial Effects." Polymers 15, no. 16 (2023): 3469. http://dx.doi.org/10.3390/polym15163469.

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In this work, we focused on synthesizing and assessing novel chitosan-based antibacterial polymers and their nanoparticles by incorporating benzothiazole substituents. The growing resistance to antibiotics has necessitated the search for alternative antimicrobial compounds. This study aimed to synthesize and evaluate chitosan-based polymers and nanoparticles with benzothiazole substituents for their antibacterial properties and toxicity. The benzothiazole derivatives of chitosan and their nanoparticles were synthesized through electrochemical coupling. The in vivo antibacterial efficacy was tested on white rats with induced peritonitis using a microbial suspension containing S. aureus and E. coli. Additionally, in vitro and in vivo toxicity assessments were conducted. The chitosan-based antibacterial systems showed significant in vivo antibacterial activity, surpassing that of unmodified chitosan and commercial antibiotics. Moreover, the toxicity studies revealed low toxicity levels of the synthesized derivatives, which did not differ significantly from native chitosan. The synthesized chitosan-based polymers and nanoparticles demonstrated potent antibacterial activity and low toxicity, highlighting their potential as effective alternatives to traditional antibiotics. Further investigations in pharmacology and preclinical trials are recommended to explore their application in clinical settings.

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Iñesta Vaquera, Francisco, Febe Ferro, Michael McMahon, Colin J. Henderson, and C. Roland Wolf. "Potential of in vivo stress reporter models to reduce animal use and provide mechanistic insights in toxicity studies." F1000Research 11 (October 11, 2022): 1164. http://dx.doi.org/10.12688/f1000research.123077.1.

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Abstract:

Chemical risk assessment ensures protection from the toxic effects of drugs and manmade chemicals. To comply with regulatory guidance, studies in complex organisms are required, as well as mechanistic studies to establish the relevance of any toxicities observed to man. Although in vitro toxicity models are improving, in vivo studies remain central to this process. Such studies are invariably time-consuming and often involve large numbers of animals. New regulatory frameworks recommend the implementation of “smart” in vivo approaches to toxicity testing that can effectively assess safety for humans and comply with societal expectations for reduction in animal use. A major obstacle in reducing the animals required is the time-consuming and complexity of the pathological endpoints used as markers of toxicity. Such endpoints are prone to inter-animal variability, subjectivity and require harmonisation between testing sites. As a consequence, large numbers of animals per experimental group are required. To address this issue, we propose the implementation of sophisticated stress response reporter mice that we have developed. These reporter models provide early biomarkers of toxic potential in a highly reproducible manner at single-cell resolution, which can also be measured non-invasively and have been extensively validated in academic research as early biomarkers of stress responses for a wide range of chemicals at human-relevant exposures. In this report, we describe a new and previously generated models in our lab, provide the methodology required for their use and discuss how they have been used to inform on toxic risk. We propose our in vivo approach is more informative (refinement) and reduces the animal use (reduction) compared to traditional toxicity testing. These models could be incorporated into tiered toxicity testing and used in combination with in vitro assays to generate quantitative adverse outcome pathways and inform on toxic potential.

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Journal articles on the topic 'In vivo toxicity studies'

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