Dissertations / Theses on the topic 'Selenomethionin'

Úprava biomasy je jedním z nejdůležitějších problémů v moderních přírodních vědách, protože je základní kategorií týkající se zemědělství, potravinářství, ekologie, zpracování odpadu a biotechnologie. Ať už živočišného, rostlinného nebo mikrobiálního původu, biomasa představuje obrovský zdroj surovin jako potravin, čistých chemikálií, bioaktivních molekul atd., jejichž izolace, charakterizace a formulace může vést k zajímavým novým produktům určeným pro lidskou spotřebu, nebo jako nový materiál v biomedicíně. Předložená studie byla zaměřena na výzkum dvou druhů biomasy - kuřecí kůže jako zdroje kolagenu t a biomasy mikrořasy Chlorella sorokiniana obohacené selenomethioninem (SeMet). V první části práce byl z kuřecí kůže izolován, identifikován a charakterizován kolagen typu I. Molekulární vlastnosti kuřecího kolagenu byly analyzovány a srovnány s jinými kolageny z živočišných kůží. Pro molekulární charakterizaci kolagenu byla použita viskosimetrie a ultrazvuková spektroskopie. Ultrazvukovou spektroskopií bylo zjištěno, že disagregace a zkapalňování hovězího kolagenu začíná při teplotě 40 °C, zatímco u kuřecího kolagenu začíná až při 50 °C. Viskosimetrie dále potvrdila vyšší tepelnou stabilitu kolagenu z kuřecí kůže, jeho denaturační teplota byla 50 °C, což je rovněž o deset stupňů více než u hovězího kolagenu. Kuřecí kolagen obsahuje dvakrát vyšší množství lysinu, což poskytuje tepelnou stabilitu kolagenu. Na základě získaných výsledků lze říci, že vzhledem ke své vysoké tepelné stabilitě a vhodnému aminokyselinovému složení, kuřecí kůže může být použita jako alternativní zdroj kolagenu typu I s aplikacemi v potravinářském průmyslu a biomedicíně. Druhá část práce byla zaměřena na obohacení biomasy zelené mikrořasy C. sorokiniana selenomethioninem. Experimentální část byla provedena v Laboratoři biotechnologie řas na Univerzitě Huelva ve Španělsku. Cílem první části experimentů bylo studovat vliv selenu na životaschopnost řas, morfologii buněk a akumulaci SeMet v biomase mikrořasy kultivované v dávkových kulturách. Subletální koncentrace Se v živném médiu, 40 mgL-1 (212 M), snížila rychlost růstu o 25 % ve srovnání s kontrolní kulturou. Hodnota EC50 45 mgL-1 (238,2 M) byla stanovena pro selenan. Ultrastrukturální studie ukazovaly na strukturální změny chloroplastu (granulární stroma, redukce thylakoid). Elektroforéza proteinů z biomasy mikrořasy ukazuje, že Se ovlivňuje expresi genu enzymu Rubisco. C. sorokiniana byla schopna akumulovat až 140 mgkg-1 SeMet během 120 h kultivace. Další část experimentální práce byla zaměřena na obohacování biomasy mikrořasy C. sorokiniana selenomethioninem během kontinuální kultivace s použitím 2,2 L bioreaktoru v kultivačním médiu s přídavkem koncentrace selenu v rozmezí od 5 do 50 mgL-1. C. sorokiniana rostla stejně ve všech testovaných koncentracích selenu kromě koncentrace 50 mgL1, která byla již po krátké době kultivace letální. Během kontinuální kultivace se 40 mgL-1 selenu, bylo získáno maximálně 246 gL-1 selenomethioninu denně. Výsledky ukazují, že kultivace v dávkových kulturách a dlouhodobá kontinuální kultivace mikrořasy C. sorokiniana pro získaní biomasy obohacené SeMet je možná pečlivým výběrem podmínek kultivace a subletálních koncentrací selenu v živném médiu.

The effects of dietary methionine (Met) on the utilization of selenium (Se) from stored tissue Se and dietary selenomethionine (SeMet) for glutathione peroxidase (GSH-Px) synthesis were studied in male rats. Plasma, liver and muscle Se significantly increased when rats were fed 0.5 mg Se/kg diet as SeMet in a Met-deficient diet for 21 d, whereas tissue GSH-Px activities decreased 43-50% during the SeMet supplementation period, suggesting that Se is deposited as SeMet in general body proteins. By calculation, a significant lower percentage of Se was associated with GSH-Px in Met-deficient as compared to Met-supplemented rats. Dietary Met supplementation increased the incorporation of 75Se from 75SeMet into specific rat selenoproteins in addition to liver GSH-Px. Overall, these results suggest that intact SeMet is preferentially incorporated non-specifically into general body proteins in Met-deficient rats, whereas with supplemental Met, more SeMet is degraded and the released Se used for specific selenoprotein synthesis. (Abstract shortened with permission of author.)

Selenomethionine, an organic derivative of selenium, has been found to be the predominate selenium component of the dietary cancer chemopreventive agent selenized yeast that has been shown to decrease the incidence and mortality rate of lung, colon, and prostate cancers. Another organic selenium derivative found in the selenized yeast is Se-methylselenocysteine. However, the mechanism of action of the anti-cancer effects of these selenium compounds has yet to be identified. To evaluate the effects of these compounds on growth of the cancer cell types mentioned earlier, various cancer cell lines were treated with either compound. Both selenium compounds were able to induce growth inhibition and alterations in the cell cycle, with selenomethionine being the most potent. Previously, our laboratory has shown that treating cancer cells with selenomethionine depleted polyamines. Polyamines are cations that are needed for various roles in growth and proliferation. To extend these findings to an in vivo model, we gave selenomethionine in the diet (1ppm and 2ppm) for 16 weeks to male F344 rats in the azoxymethane (AOM) rat colon carcinogenesis model. The results showed no significant changes in colonic polyamine levels, however, there were significant changes in the development of microadenomas between control and treated groups. Selenomethionine was able to decrease the promotional effects of colon carcinogenesis through a polyamine-independent mechanism. Next, we tested the hypothesis that selenomethionine might affect cell growth by mechanisms involving cyclooxygenases, specifically the inducible isoform COX-2. Cyclooxygenases (COX-1 and COX-2) are enzymes that metabolize arachidonic acid to various prostaglandins. The human adenocarcinoma cell lines HT-29 and HCA-7, that express variable levels of COX-2, were treated for up to 6 days with selenomethionine. Selenomethionine induced growth inhibition in both cell lines and decreased COX-2 protein expression in the treated groups. Also, prostaglandin (PG) E2 levels were decreased in both treated groups at the latter timepoints. The HCA-7 cell line had a dose and time-dependent decrease in RNA levels treated with selenomethionine, whereas, no effects were observed on RNA expression of the HT-29 cell line. In summary, selenomethionine has chemopreventive effects in colon carcinogenesis by potentially modulating COX-2 proteins in cancer cells.

Orientador: Rodrigo Yudi Fujimoto
Banca: Claudinei da Cruz
Banca: Eduardo Makoto Onaka
Resumo: O Selênio é um mineral constituinte de uma série de enzimas antioxidantes que atuam protegendo as membranas celulares dos danos causados pelo processo de oxidação. Sua deficiência ou excesso na dieta pode resultar em depressão do crescimento e aumento da taxa de mortalidade. O objetivo deste estudo foi avaliar o efeito da suplementação da dieta em jovens de tilápia do Nilo (Oreochromis niloticus) com quatro níveis de selenometionina (0,25; 0,50; 1,0; e 1,5 mg Se/kg) e um grupo controle (0,0 mg Se/kg) no desempenho produtivo (ganho de peso, conversão alimentar aparente, taxa de crescimento específico e consumo de ração), nos índices hepatossomático e esplenossomático, na histopatologia do fígado, no índice de parasitismo por monogenea e na hematologia. O consumo de ração aumentou proporcionalmente ao nível de Se nas dietas. Os índices de desempenho produtivo não apresentaram diferenças significativas, no entanto, as concentrações intermediárias (0,25 e 0,50 mg Se/kg) aumentaram o ganho de peso, diminuíram a conversão alimentar e não apresentaram alterações significativas no estrutura morfofuncional do fígado. Não ocorreu diferença significativa para as variáveis hematológicas estudadas e para o índice de parasitismo por monogenea, porém, observou-se que nos níveis de 0,50 e 1,0 mg Se/kg o número de parasitos foi menor em relação às demais concentrações. Assim, pode-se concluir que a melhor suplementação está entre os níveis de 0,25 e 0,50 mg Se/kg de ração.
Abstract: Selenium is an important micronutrient for animals, essential for the normal life processes. This mineral is a constituent of the enzyme antioxidant glutathione peroxidase, of deiodinase and of thioredoxin reductase. The deficiency or toxic levels in feed can be result in growth depression and mortality. The objective of this study was to evaluate the selenomethionine effects for juveniles Nile tilapia (Oreochromis niloticus) on the growth performance (weight gain, index of alimentary conversion, specific growth rate, diet consumption and index of alimentary efficiency), hepatossomatic and esplenossomatic index, liver histopathology, parasitism and haematology, submitted to four levels of selenium in feed (0.25, 0.50, 1.0, and 1.5 mg Se/kg diet) and control group (0.0 mg Se/kg). The results did not show difference, however, the levels of 0.25 and 0.50 mg Se/kg improve the growth performances evaluated and did not show liver histopathology damage. No differences were observed in haematological parameters. The total count of monogeneans reduced in the levels of 0.50 and 1.0 mg Se/kg of diet but without differences due the elevated coefficient of variation. In conclusion the ideal supplementation level was between 0.25 and 0.50 mg Se/kg.
Mestre

Made available in DSpace on 2014-06-11T19:22:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-07-18Bitstream added on 2014-06-13T19:48:38Z : No. of bitstreams: 1 gomes_gr_me_jabo.pdf: 339770 bytes, checksum: dd4a8375e7eb01472c1aff691990e379 (MD5)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O Selênio é um mineral constituinte de uma série de enzimas antioxidantes que atuam protegendo as membranas celulares dos danos causados pelo processo de oxidação. Sua deficiência ou excesso na dieta pode resultar em depressão do crescimento e aumento da taxa de mortalidade. O objetivo deste estudo foi avaliar o efeito da suplementação da dieta em jovens de tilápia do Nilo (Oreochromis niloticus) com quatro níveis de selenometionina (0,25; 0,50; 1,0; e 1,5 mg Se/kg) e um grupo controle (0,0 mg Se/kg) no desempenho produtivo (ganho de peso, conversão alimentar aparente, taxa de crescimento específico e consumo de ração), nos índices hepatossomático e esplenossomático, na histopatologia do fígado, no índice de parasitismo por monogenea e na hematologia. O consumo de ração aumentou proporcionalmente ao nível de Se nas dietas. Os índices de desempenho produtivo não apresentaram diferenças significativas, no entanto, as concentrações intermediárias (0,25 e 0,50 mg Se/kg) aumentaram o ganho de peso, diminuíram a conversão alimentar e não apresentaram alterações significativas no estrutura morfofuncional do fígado. Não ocorreu diferença significativa para as variáveis hematológicas estudadas e para o índice de parasitismo por monogenea, porém, observou-se que nos níveis de 0,50 e 1,0 mg Se/kg o número de parasitos foi menor em relação às demais concentrações. Assim, pode-se concluir que a melhor suplementação está entre os níveis de 0,25 e 0,50 mg Se/kg de ração.
Selenium is an important micronutrient for animals, essential for the normal life processes. This mineral is a constituent of the enzyme antioxidant glutathione peroxidase, of deiodinase and of thioredoxin reductase. The deficiency or toxic levels in feed can be result in growth depression and mortality. The objective of this study was to evaluate the selenomethionine effects for juveniles Nile tilapia (Oreochromis niloticus) on the growth performance (weight gain, index of alimentary conversion, specific growth rate, diet consumption and index of alimentary efficiency), hepatossomatic and esplenossomatic index, liver histopathology, parasitism and haematology, submitted to four levels of selenium in feed (0.25, 0.50, 1.0, and 1.5 mg Se/kg diet) and control group (0.0 mg Se/kg). The results did not show difference, however, the levels of 0.25 and 0.50 mg Se/kg improve the growth performances evaluated and did not show liver histopathology damage. No differences were observed in haematological parameters. The total count of monogeneans reduced in the levels of 0.50 and 1.0 mg Se/kg of diet but without differences due the elevated coefficient of variation. In conclusion the ideal supplementation level was between 0.25 and 0.50 mg Se/kg.

A nutrição para matrizes de frangos de corte tem como objetivo maximizar a produção de ovos e a qualidade da progênie subsequente e é considerada essencial para a melhora da produção e qualidade dos ovos. Os nutrientes transferidos para os ovos são importantes para o crescimento e desenvolvimento fisiológico do embrião. O organismo animal sofre constantemente ação do estresse oxidativo e o selênio (Se) é considerado um eficiente antioxidante natural que é essencial para matrizes de frangos de corte. Este estudo foi conduzido com matrizes de frango de corte alimentadas com duas fontes de Se (selenometionina - orgânica e selenito de sódio - inorgânico) para avaliar o seu desempenho produtivo, as características reprodutivas, a concentração de Se no ovo bem como o desempenho e rendimento de carcaça da progênie subsequente. Foram utilizadas 216 matrizes AP95 Aviagen de 55 a 65 semanas de idade, em delineamento inteiramente casualizado, com dois tratamentos e 27 repetições de quatro aves cada. Para o experimento com a progênie, foram utilizados 520 pintinhos mistos em delineamento inteiramente casualizado em um fatorial 2 x 2 (duas fontes de Se da dieta das matrizes e duas fontes de Se para dietas de frangos de corte - selenito de sódio e selenometionina) com quatro tratamentos, 13 repetições de 10 aves cada. As matrizes alimentadas com Se orgânico melhoraram a produção de ovos em comparação com o Se inorgânico (p = 0,038; p = 0,044). A concentração do Se no ovo e na clara foi maior para Se orgânico em comparação com o inorgânico (p <0,001; p <0,001). As taxas de fertilidade, bem como mortalidade embrionária, não sofreram efeito significativo ao se comparar as duas fontes. Não foram observadas diferenças entre a altura de albúmen, unidade Haugh e espessura da casca para a qualidade do ovo. O peso do ovo e coloração da gema foram estatisticamente diferentes (p=0,001; p=0,026) para fonte inorgânica comprada com a orgânica. A resistência a quebra do ovo foi melhor estatisticamente (p=0,007) para fonte orgânica. Não foram observadas interações entre a dieta da progênie e a dieta materna para nenhum dos critérios avaliados. Não foram observados efeitos da dieta materna, assim como da dieta da progênie sobre o consumo de ração, ganho de peso corporal e rendimento de carcaça e cortes. No entanto, a taxa de conversão alimentar foi melhor (p = 0,017) em frangos de corte provenientes de matrizes alimentadas com selenometiona. Assim, a selenometionina melhorou a produção e qualidade de ovos e propiciou maior transferência de Se para o ovo, principalmente na clara. Além disso, melhorou a conversão alimentar da progênie, devido a sua melhor biodisponibilidade.
The nutrition for broiler breeders has the objective of maximizing egg production and the quality of subsequent progeny. It is essential to improve the egg production and egg quality. The nutrients transferred to the eggs are important for growth and physiological development embryo. The animal organism is constantly suffering by oxidative stress. Selenium (Se) is considered an efficient natural antioxidant and has shown to be essential for broiler breeders. This trial was conducted using broiler breeders fed with two different sources of Se (organic - selenomethionine and inorganic - sodium selenite) to determinate performance, reproductive characteristics, Se concentration in egg as well as performance and carcass yield of the subsequent progeny. It was used 216 AP95 Aviagen broiler breeders, from 55 to 65 weeks of age, in completely randomized design with two treatments and 27 replications of four birds each. For subsequent progeny, it was used 520 straght-run chicks in a completely randomized design in a 2 x 2 factorial (two sources of Se for broiler breeders diets and two sources of Se for broilers diets- sodium selenite and selenomethionine) with four treatments and 13 replications of 10 birds each. Broiler breeders fed with organic Se had improved egg production in comparison to inorganic Se (p=0.038; p=0.044). Se concentration in whole egg and white egg were higher for organic Se in comparison to inorganic Se (p<0.001; p<0.001). The fertility and embryonic mortality were not significant between Se sources. No difference were observed to albumin height, Haugh unit and shell thickness for egg quality. The egg weight and yolk color were statistically different (p = 0.001; p = 0.026) for inorganic source compering to organic. The egg breaking was statistically better (p=0.007) for organic source. For progeny, no interactions between broiler diet and the maternal diet were observed for any of the criteria measured. No effect of maternal diet as well as broiler diet differences were observed on feed intake, body weight gain and carcass yield and cuts. However, feed conversion ratio was improved (p=0,017) in broiler from breeders fed selenomethione. Thus, selenomethionine has improved the egg production and quality, and has been transferred to the egg mainly in the egg white. Also, selenomethionine has improved feed conversion ratio because has a higher bioavailability.

Påväxt på båtar och andra föremål som sätts ner i vattnet är ett stort och kostsamt problem världen över. I Sverige orsakar havstulpanen, Balanus improvisius, den största påväxten. Havstulpanen har många förstadier innan den blir en vuxen havstulpan. I det stadiet innan den sätter sig fast på olika platser, kallas den cyprid. Det tar mellan tre dagar och upp till några veckor innan cypriden valt plats att settla på. Den väljer plats mycket noggrant då den skall tillbringa resterade delen av sitt liv på denna.

Mycket forskning läggs ner på att finna ett alternativ till dagens giftiga båtbottenfärger. Tennorganiska föreningar, som använts för att motverka settling på båtbottnar, blir totalförbjudet 1 januari, 2008. Nu mer tillsätts allt oftare kopparföreningar istället vilket inte är någon större förbättring för miljön. Det finns idag många miljövänliga färger, som t.ex. silikonbaserad färg, men de fungerar inte lika bra som färgerna med metaller. Det forskas även på om ytan på båtbotten skall kunna förändras mekaniskt, för att motverka havstulpanens settling.

De substanser som är testade i denna rapport är selenmetionin och nitroglycerin. De testades i olika koncentrationsintervaller och i olika blandningar med varandra. Med en förhoppning om att selenmetioninen binder in i föreningar och då att hastigheten för reaktioner med tioler kan minska drastiskt och leda till gifteffekter, och att nitroglycerinen skall pacificera cypriden genom att binda till hemoglobinet istället för syre, skall dessa två substanser hålla cypriderna borta från båtbottnarna. Med föraningar om att substanserna har en synergistisk effekt då de blandas, skall lägre koncentrationer kunna användas. Då för höga koncentrationer är kostsamt och har troligen större negativ påverkan på miljön.

Selenmetionin visade en antydan till att minska settling men nitroglycerinen hade en mer främjande effekt på cypridens settling. Det visade sig även att substanserna hade en synergistisk effekt och därmed kan koncentrationerna för substanserna sänkas.

Biological growth on boats and other objects that are placed in water is a big and expensive problem over the entire world. In Sweden, the barnacle, Balanus improvisius, grows the most easily. This barnacle has many larvae stages before it becomes mature. During the larvae stage when it searching for a surface to settle on it is called cyprid. It takes between three days and a couple of weeks before a cyprid chooses a spot to settle on. It chooses the spot to settle on very carefully because it will spend the rest of its life on that exact place.

A lot of research goes into to finding a good alternative to today’s toxic boat paints. Tin organic compounds, as used to counteract settling of cyprids on boats, will be totally forbidden in January, 2008. As a replacement, copper compounds are being added more often to paints. These are not much better for the environment. Today there are many environmentally friendly paints, as for example silicon-based paint, but they do not work as well as the paints with metals. Research is also looking at mechanically changing a boat’s surface so that barnacles cannot attach as easily.

The substances that are tested in this report are selenomethionine and nitro glycerine. They were tested in different concentration intervals and in different mixes with each other with the hope of that selenomethionine will bound into compounds and then the reaction velocity with thioles will be reduced and give toxic effects. The nitro glycerine will make the barnacle passive through the idea that the NO is binding into a heme group instead of oxygen. It was hoped that the substances show a synergistic effect when they are mixed, allowing lower concentrations to be used. With too high concentrations in the paint, the paint becomes too expensive and likely has a bigger negative influence on the environment.

Selenomethionine showed an indication to reduce the likelihood that barnacles would settle on a pained surface, but nitro glycerine, on the other hand, caused an increased rate of cyprid settling. It was also shown that the substances had a synergistic effect and thus the concentrations for the substances can be lowered.

Tyrimų problema: vitaminas E ir selenas yra plačiai naudojami maisto papildai gerinant žmonių sveikatingumą. Tarpusavyje šie elementai pasižymi stipriu sinergetiniu veikimu. Vitamino E ir seleno transferacijos laipsnis iš lesalų į paukštieną yra sąlygojamas daugelio faktorių, kaip seleno ir vitamino E formų bei kiekių, sąveikos su kitais mikroelementais bei organinėmis rūgštimis, fitobiotikais, sintetiniais antioksidantais, lesalų gamybos technologinių procesų, paukščių auginimo sąlygų, jų imuniteto ir kt.. Todėl magistrinio darbo tikslas yra ištirti skirtingų vitamino E kiekių, naudojant selenitą ir selenometioniną, įtaką viščiukų broilerių produktyvumui, fiziologinei būklei bei paukštienos kokybei. Uždaviniai: 1.Nustatyti skirtingo vitamino E ir skirtingų koncentracijų seleno bei seleno formų įtaką viščiukų broilerių augimo intensyvumui, lesalų konversijai bei išsaugojimui. 2.Nustatyti skirtingo vitamino E ir skirtingų koncentracijų seleno bei seleno formų įtaką viščiukų broilerių fiziologinei būklei. 3.Nustatyti skirtingo vitamino E ir skirtingų koncentracijų seleno bei seleno formų įtaką viščiukų broilerių mėsos kokybei. Svarbiausios išvados: 1.Naudojant organinį seleną 0,3 mg/kg ir vitaminą E 70 mg/kg tiriamųjų viščiukų broilerių masė padidėjo 5,2% (p<0,05), lesalų konversija pagerėjo 5,2% ir viščiukų išsaugojimas padidėjo 4% palyginus su kontroline grupe. 2.Analizuojant tiriamosios grupės viščiukų broilerių kraujo rodiklius nustatėme, kad esminių skirtumų tarp... [toliau žr. visą tekstą]
The issue of investigation: vitamin E and selenium transferacion degree of feed to poultry is caused by many factors such as selenium and vitamin E forms and levels of interaction with other microelements, organic acids, phytobiotics, synthetic antioxidants, feed manufacturing processes, chicken broilers growing conditions, their immunity, etc.. Therefore, the aim of the Master is to investigate the different levels of vitamin E, using selenite and selenomethionine, on chicken broilers productivity, physiological condition and poultry quality. The tasks of the work: 1. To determine different vitamin E and selenium concentrations and different forms of selenium influence for chicken broilers growth rate, feed conversion and surviving. 2. To determine different vitamin E and selenium concentrations and different forms of selenium influence for chicken broilers physiological conditions. 3. To determine different vitamin E and selenium concentrations and different forms of selenium influence for chicken broilers meat quality. The most important conclusions: 1. When organic selenium 0.3 mg/kg and vitamin E 70 mg/kg was used, the weight of experimental broiler group increased 5.2% (p <0.05), feed conversion improved 5.2%, chicken surviving increased 4% in comparison with the control group. 2. The analysis of the blood parameters in a experimental group of chicken broilers showed that there wasn’t any substantial differences in cholesterol, HDL and LDL. However, the experimental... [to full text]

O experimento foi conduzido na FZEA/USP com objetivo de comparar a utilização de fontes orgânicas de selênio (Se) com o selenito de sódio na dieta de cordeiros, pela análise da concentração de Se nos tecidos, da atividade da enzima glutationa peroxidase no fígado, do balanço metabólico e do cálculo da biodisponibilidade. Foram utilizados 40 cordeiros Suffolk, os quais foram submetidos a três fontes e três níveis de Se suplementar por 84 dias. Os tratamentos foram: tratamento 1: sem suplementação; tratamentos 2, 3 e 4: 0,2; 0,8 e 1,4 mg/kg de Se suplementar na forma de selenito de sódio; tratamentos 5, 6 e 7: 0,2; 0,8 e 1,4 mg/kg de Se suplementar na forma de Se-levedura; tratamentos 8, 9 e 10: 0,2; 0,8 e 1,4 mg/kg de Se suplementar na forma de Se-metionina. Foram colhidas amostras de sangue para dosagem sérica de Se e ao final do experimento, os animais foram abatidos para colheita de amostras de fígado, músculo e rim, para determinação dos teores de Se e da atividade da glutationa peroxidase (fígado). Nos últimos cinco dias de experimento foi realizado um balanço metabólico de Se. A biodisponibilidade foi calculada através da técnica “slope ratio”, utilizando como parâmetros a concentração de selênio no fígado, músculo, rim e a atividade da glutationa peroxidase. Não houve efeito da fonte de Se utilizada na ingestão, absorção aparente e retenção de Se, atividade da glutationa peroxidase e nas concentrações de selênio no fígado, rim e soro; porém, as concentrações de selênio no músculo foram maiores nos animais suplementados com fontes orgânicas do que nos outros animais (P<0,0001). A biodisponibilidade de Se no músculo foi maior quando foram utilizadas fontes orgânicas de selênio. O uso de fontes orgânicas de Se promove maior acúmulo de Se no músculo de cordeiros e promoveria maior ingestão de Se por consumidores de carne ovina.
This research was carried out at FZEA/USP to compare the utilization of organic selenium (Se) sources to sodium selenite in lambs’ diet, through analyses of tissues Se concentrations, liver glutathione peroxidase activity, metabolic balance of Se and bioavailability assay. Forty Suffolk lambs were used and submitted to three sources and three levels of supplementary Se for 84 days. Treatments were: treatment 1: no supplement; treatments 2, 3 and 4: 0.2, 0.8 and 1.4 mg/kg of supplementary sodium selenite-selenium; treatments 5, 6 and 7: 0.2, 0.8 and 1.4 mg/kg of supplementary selenoyeast-selenium; treatments 8, 9 and 10: 0.2, 0.8 and 1.4 mg/kg of supplementary selenomethionine-selenium. Blood samples were taken to Se serum dosage and in the end of the experiment the animals were killed and samples of liver, muscle and kidney were taken to Se concentrations dosage and glutathione peroxidase activity (liver). In the last five days of the experiment, a Se metabolic balance was realized. Bioavailability was calculated by “Slope Ration Assay”, using liver, muscle and kidney Se concentrations and glutathione peroxidase activity as parameters. Se sources did not affect Se intake, apparent absorption and retention, glutathione peroxidase activity and Se concentrations in liver, kidney and serum; however, selenium concentrations in muscle of animals supplied with organic sources were higher than in other animals (P<0.0001). Se bioavailability in muscle was higher when organic Se sources were used. Using organic Se sources provides higher accumulation of Se in lambs’ muscle which would provide higher Se intake to consumers of sheep meat.

Tout au long de la chaîne alimentaire, des moisissures peuvent se développer et produire des mycotoxines. Ce sont des composés toxiques naturels issus du métabolisme secondaire des moisissures, susceptibles de contaminer l'alimentation animale et humaine, provoquant de nombreuses pathologies (hépatotoxicité, néphrotoxicité, neurotoxicité, mutagénicité, tératogénicité, cancérogénicité,…). La première étape de ce travail était d'évaluer la présence simultanée de l'ochratoxine A (OTA), de la citrinine (CIT), des aflatoxines (AFs), de la zéaralénone (ZEA), de la fumonisine (FB) et des trichothécènes dans des aliments destinés aux humaines (céréales, lait, café, jambon) et aux animaux (croquettes de chat et chien, foins). En général plusieurs mycotoxines coexistaient. Certains échantillons pour les humains dépassaient les limites autorisées en mycotoxines dans l'Union Européenne. Suite à l'étude de simulation d'apport en mycotoxines dans une ration quotidienne, nous avons constaté que les doses journalières admissibles (DJA) peuvent être dépassées. La deuxième phase consistait à étudier l'impact des mycotoxines seules ou en combinaison sur la viabilité cellulaire et la génotoxicité sur des modèles cellulaires (cellules rénales d'opossum (OK), cellules rénales humaines (HK2), cellules humaines de glandes mammaires (MCF7)) et chez des animaux (porc, rat). Nous avons montré que la CIT, la FB1 et la ZEA agissent en synergie sur la génotoxicité de l'OTA. Chez les animaux, nous avons montré qu'à des doses (5 ng d'OTA/kg poids corporel/ jour et de 200ng FB1/kg pc/j) correspondantes aux DJA, il y avait des effets génotoxiques (formation d'adduits à l'ADN). Nous avons mis en évidence l'implication des mycotoxines dans l'alimentation animale sur la baisse de fertilité et la tératogénicité chez les chats, ainsi que sur la mort des chevaux. Au cours de la troisième partie de cette étude, nous avons testé sur des cultures cellulaires (HK2 et MCF7) et in vivo (poulet) l'effet protecteur du glutathion (GSH) et de la sélénométhionine (SeMet) contre l'OTA responsable de cancers de voie urinaire et la ZEA responsable de baisse de fertilité. Le GSH est un puisant antioxydant et le sélénium est un oligoélément indispensable qui intervient comme co-facteur de nombreuses enzymes ayant des propriétés antioxydantes, comme les glutathion peroxydases. D'une manière générale, au niveau des cellules rénales, le GSH seul et la levure correspondante ont un effet bénéfique vis-à-vis de la génotoxicité de l'OTA ; par contre la sélénométhionine et la levure séléniée augmentent la génotoxicité de l'OTA et de la ZEA. Dans les cellules des glandes mammaires, il y a une nette amélioration vis-à-vis de la génotoxicité des deux mycotoxines lorsque les cellules sont exposées à une seule mycotoxine simultanément au GSH, à la sélénométhionine et aux levures enrichies. Chez les poulets, la diminution de la génotoxicité n'est pas exclusivement corrélée à la capacité des parois de levure ou des levures à adsorber l'OTA. Ces dérivés de levure ont gardé la propriété de partiellement métaboliser l'OTA dans l'intestin. Les parois de levures et les levures enrichies en GSH ont un meilleur pouvoir protecteur que celles enrichies en SeMet
Throughout the food chain, mold can grow and produce mycotoxins. These are toxic compounds "natural" from the secondary metabolism of molds that may contaminate the feed and food, causing many diseases (hepatotoxicity, nephrotoxicity, neurotoxicity, mutagenicity, teratogenicity, carcinogenicity, ...). The first stage of this work was to assess the level of multi-contamination by mycotoxins (OTA, CIT, Afs, ZEA, FB, DON) in food (cereals, milk, coffee, ham) and feed (pet food). Some samples analyzed exceeded the limits of mycotoxins in the European Union. Through the simulation study of mycotoxin intake in a daily diet, we found that the acceptable daily intake (ADI) may be exceeded. The second phase was to study the impact of mycotoxins alone or in combination on cell proliferation, genotoxicity in cellular models (OK, HK2, and MCF7) and animal (pig, rat). We have demonstrated genotoxic effects (formation of DNA adducts) at doses (5 ng OTA / kg bw / day and 200 ng FB1/kg bw / day) considered safe (ADI). We have shown that the CIT, FB1 and ZEA act synergistically on the genotoxicity of OTA. We pointed to the involvement of mycotoxins in animal feed on declining fertility and teratogenicity in cats, as well as the death of horses. In the third part of this study, we tested in cell cultures (HK2 and MCF7) and in vivo (chicken) the protective effect of glutathione (GSH) and selenomethionine (SeMet) against OTA responsible for urinary tract cancers and ZEA reducing fertility. GSH is considered as a potent antioxidant and selenium is a trace essential element that acts as a cofactor of enzymes such glutathione peroxidase. In summary, in kidney cells, GSH and GSH enriched yeast decrease OTA genotoxicity whereas SeMet and SeMet enriched yeast increase genotoxicity of OTA and ZEA. In mammary cells, whatever the compounds gentoxicty of OTA and ZEA significantly decrease. Decrease of OTA genotoxicity in chicken kidney cannot be exclusively explained by adsorption of OTA on yeast by products. The yeast products retain their ability to metabolize the OTA. GSH enriched yeast and yeast cell wells are more efficient than SeMet enriched yeast

Le sélénium est un micronutriment essentiel pour des nombreux organismes vivants, y compris l’homme. Son rôle est lié à sa présence dans des sélénoprotéines sous forme d’un acide aminé, génétiquement encodé – la sélénocystéine. Il y a 25 sélénoprotéines encodées dans le génome humain. Leurs fonctions, la cinétique et la hiérarchie d'expression se trouvent au cœur des problématiques de recherche concernant le sélénium et la santé humaine. Il existe également un autre type de protéines où le sélénium est inséré par un remplacement partiel du soufre dans la méthionine mais aussi, potentiellement, dans la cystéine. Ces protéines suscitent l’intérêt dans les sciences de nutrition comme source de sélénium biodisponible dans l’alimentation naturelle et supplémentée. L'objectif de cette thèse a été la mise au point de méthodologies analytiques visant la spéciation du sélénium incorporé dans les protéines à l’échelle du protéome entier. Une procédure inédite a été développée pour la détection globale de protéines séléniées dans des gels d’électrophorèse bidimensionnelle par l’imagerie d’ablation laser ICP MS (spectrométrie de masse plasma à couplage inductif) permettant de s’affranchir de l’utilisation de l’isotope radioactif 75Se. Les autres avancées comprennent la mise en place d’un couplage robuste de HPLC capillaire avec l’ICP MS pour la détection des sélénopeptides dans des microvolumes de digestats trypsiques des protéines extraites du gel ainsi que la mise en place des protocoles d’identification des protéines séléniées par la spectrométrie de masse électrospray en tandem utilisant la trappe orbitale (Orbitrap). Les méthodes développées ont permis (i) la caractérisation de la part du protéome sélénié contenant la sélénocystéine chez la levure séléniée, (ii) l’identification des protéines majeures qui accumulent le sélénium dans le blé, et (iii) le dosage semi quantitatif et la caractérisation globale des sélénoprotéomes (GPx1, GPx4, TRxR1, TRxR2, Sel15kDa) dans les lignées cellulaires
Selenium is an essential micronutrient for many living organisms including man. Its role is related to selenoproteins which contain genetically encoded selenocysteine. There are 25 selenoproteins encoded in the human genome. Their function, expression kinetics and hierarchy have been a topic of intense research in life sciences. There is another type of proteins which contain selenium inserted non-specifically by partly replacing sulphur in methionine and, potentially, cysteine. They are of interest in nutrition science as source of bio-available selenium in natural and supplemented foods. The goal of this Ph.D. was the development of methodologies for the analysis of selenium-containing proteins on the entire proteome scale. A novel procedure was developed for their global detection in 2D electrophoretic gels par laser ablation inductively coupled plasma mass spectrometry (ICP MS) imaging permitting to avoid the use of the radioactive 75Se. The other developments included (i) a robust capillary HPLC – ICP MS coupling allowing the detection of Se-containing peptides in microliter volumes of the digests of proteins extracted from the gel and (ii) protocols allowing the targeted identification of the Se-containing proteins by a parallel capillary HPLC - electrospray Orbitrap MS/MS. The methods developed allowed (i) the characterisation of the selenocystein-containing part of the selenoproteome of Se-enriched yeast, (ii) identification of the major Se-accumulating proteins in wheat, and (iii) semiquatitive analysis and global identification of the selenoproteomes (GPx1, GPx4, TRxR1, TRxR2, Sel15kDa) expressed in different human cell lines

Selenium (Se) is an essential trace element to most living organisms, however when compared to other ingested essential trace elements Se has the lowest margin of safety between essential and toxic concentrations. Oviparous vertebrates, especially fishes, are highly susceptible to dietary Se toxicity. Greater incidences of deformities and/or mortalities have been observed in F1 generation larval fishes whose parents were exposed to excess dietary Se in the form of selenomethionine (SeMet), however little information is available on effects of chronic dietary SeMet exposure to adult fish and persistent effects of in ovo SeMet exposure to F1 generation fish. This thesis investigated effects of chronic dietary exposure of excess Se in the form of SeMet on swimming performance (Ucrit), oxygen consumption (MO2), stored energy (triglycerides and glycogen), and the physiological stress response (cortisol production) in adult zebrafish (Danio rerio), as well as immediate (incidence of deformities and mortality) and persistent (e.g. changes in Ucrit, MO2, bioenergetics, the physiological stress response and reproduction) effects of in ovo exposure to SeMet in F1 generation zebrafish. In addition, the study investigated potential underlying mechanisms of SeMet-induced developmental toxicities in early life stages of zebrafish using embryo microinjection. Two separate dietary SeMet exposure studies in adult zebrafish and two in ovo SeMet maternal transfer studies in F1 generation zebrafish were conducted. The first dietary or in ovo exposure study explored effects of excess SeMet exposure on adult zebrafish or the entire life cycle of F1 generation zebrafish. The second study investigated mechanisms of observed SeMet-induced effects on adult or F1 generation zebrafish. In the first feeding study, a significant reduction in Ucrit and greater accumulation of stored energy were observed in the excess dietary SeMet exposed groups when compared to the Se-sufficient dietary control group. The second feeding study showed a greater metabolic rate, and impaired aerobic energy metabolism and triglyceride homeostasis in adult fish fed excess dietary SeMet, which was associated with a reduction in swimming performance and accumulation of triglycerides. Embryos collected from adult zebrafish in both dietary SeMet exposure studies were used to investigate effects of in ovo SeMet exposure on the entire life cycle of F1 generation fish. The first study showed a greater incidence of mortality, an increasing trend for deformities in F1 generation larval zebrafish, and reduced Ucrit in F1 generation adult fish exposed to excess SeMet via in ovo maternal transfer. However, concentrations of stored energy, cortisol and reproduction were unaltered. The second study found that impaired aerobic performance might have been responsible for the reduction in Ucrit of F1 generation adult zebrafish exposed to excess SeMet. Since there is a high variability in Se deposition among eggs via natural maternal transfer, SeMet embryo microinjection was adopted to mimic maternal transfer and to investigate potential mechanisms of SeMet-induced developmental toxicities in early life stages of zebrafish. Greater gene expression of oxidant-inducible transcription factors and impairment in gene expression of an enzyme involved in methionine catabolism were observed in early life stages of zebrafish exposed to excess SeMet via in ovo microinjection. The research presented in this thesis suggests that environmentally relevant dietary SeMet exposure can alter physiological responses in adult fishes and reduce survivability of F1generation fishes, which could impact fitness and recruitment of wild fishes inhabiting Se-contaminated aquatic ecosystems. In addition, the study suggests that SeMet-induced developmental toxicities in early life stages of fishes might be related to oxidative stress or impaired methylation, or a combination of these mechanisms.

Sturgeon are an ancient family of fish which have remained essentially unchanged for 200 million years, rendering them physiologically distinct from the more modern teleosts. Of the 26 known species of sturgeons all are likely endangered. North American populations have been declining steadily since the 1800s due to factors such as overharvesting, habitat alterations and increasing pollution. White sturgeon (Acipenser transmontanus), endemic to Western North America, are the largest freshwater fish on the continent. Protecting white sturgeon is of interest because nearly all Canadian populations are endangered and they are culturally and economically important. Factors such as great size, longevity, position in the food chain and benthic life style render white sturgeon particularly susceptible to bioaccumulation of toxicants. They are known to be among the most sensitive species to pollutants such as metal ions, dioxin-like compounds and endocrine disrupters. However, little is known about their susceptibility to other priority contaminants such as selenium (Se). Selenium, in its organic form selenomethionine (SeMet) has become a contaminant of particular concern as it is a known toxicant that efficiently bioaccumulates and biomagnifies in the food chain. It is also of interest as Se is an essential micronutrient that becomes toxic at only marginally greater than optimal doses. Current elevated concentrations of SeMet in white sturgeon prey, with predicted increases in anthropogenic releases, have made it a contaminant of concern for this species. It is hypothesized that increased releases of Se to aquatic environments have contributed in part to sturgeon declines; however, to date little is known about its specific effects on this species. Therefore, the purpose of the present study was to investigate the sensitivity of three year old white sturgeon to dietary SeMet and to link physiological effects to key molecular events of toxicity and to elucidate the mechanism of toxicity. Specifically, this thesis focused on oxidative stress in liver tissue as a hypothesized primary mechanism of toxicity. For 72 days sturgeon were given either a control diet of 1.4 µg Se/g feed or a diet spiked with SeMet (5.6, 22.4 or 104.4 µg Se/g feed dry mass). These doses corresponded to an uptake necessary for proper health, two environmentally relevant exposures, and a worst-case scenario for industrial Se release, respectively. A subsample of fish was taken at day 10 to investigate molecular endpoints. Within 10 days of exposure, pathological effects were observed in fish given the high dose. Occurrence of severe edema causing exophthalmos developed within 15, 23 and 52 days in high, medium and low dose group fish, respectively. There was a 54% and 22% occurrence of lethal effects in the high and medium dose groups, respectively. Se accumulated in a dose dependent manner and reached equilibrium in high dose fish after approximately 40 days. Growth, liver weight and hepatosomatic index were all significantly lower in the high dose group. Histology of 72 day liver samples showed a significant and dose dependent increase in melanomacrophage aggregates and decrease of energy stores and cell size. Food avoidance was also observed in sturgeon exposed to the high dose. To investigate oxidative stress, 10 day liver samples were tested for changes in gene expression coding for glutathione peroxidase (GPx), superoxide dismutase, catalase, glutathione S-transferase, apoptosis inducing factor and caspase 3, using real-time PCR. Only GPx was significantly induced. Day 72 liver samples were tested for the presence of lipid hydroperoxides but there were no significant differences between dose groups and controls, which shed doubt on oxidative stress being the main driver of toxicity. Taken together the data makes a strong case for the sensitivity of white sturgeon to Se accumulation and indicates a general suppression of health due to toxic levels of exposure. However, in contrast to other fish species exposed to Se, oxidative stress is not likely the main mechanism of toxicity in white sturgeon. Findings from the present study could be used for the risk assessment of sturgeon to anthropogenic Se in aquatic ecosystems.

Selenium (Se) is a contaminant of potential concern in aquatic systems due to its efficient incorporation into food webs, potential for bioaccumulation at higher trophic levels, and role as a developmental toxicant in oviparous vertebrates. While the presence of embryonic/larval deformities due to in ovo Se exposure is considered the most sensitive toxicological endpoint, elevated levels of dietary Se have also been associated with alterations to bioenergetic and hormonal status of adult female fishes, which consequently could lead to diminished fitness and impaired reproduction. Adverse reproductive effects in fishes have been the primary focus of Se research thus far, while studies focusing on Se toxicity in amphibians in any regard are severely lacking. The US EPA has recently proposed a new set of criteria for the protection of freshwater aquatic life with regards to acceptable Se tissue threshold levels; however, these values were generated based on effects observed in fishes with negligible existent data on amphibians to assist in this process. Thus, the overall goal of this thesis research was to characterize the reproductive and developmental effects of elevated dietary Se exposure in Xenopus laevis, in order to provide a foundation for amphibian related Se research that may assist in establishing effective regulatory guidelines that protect this highly vulnerable and ecologically valuable taxon. The research presented in this thesis was performed as one large generational bioassay with the analysis of experimental variables divided into three sections in order to evaluate the effects of elevated in ovo Se exposure via maternal transfer on early and late stages of larval development in addition to the overall fitness of adult X. laevis females after a dietary exposure. Adult X. laevis females were fed a diet augmented with L-selenomethionine (SeMet) for 68 days after which they were bred with untreated males. The resultant embryos were incubated up to 5 days post fertilization (dpf) to determine fertilization success, hatchability, mortality and frequency/severity of malformations. Subsamples of 5 dpf tadpoles were selected and raised to completion of metamorphosis for evaluation of mortality, growth and maturation rate. In addition, tissue and blood samples as well as morphometric indices were collected from X. laevis females, upon completion of the exposure period and subsequent breeding, to ascertain Se tissue distribution, triglyceride and glycogen levels, cortisol concentrations and the overall health status of SeMet-treated females. Within the data gathered throughout this research, a foundation of knowledge characterizing Se toxicity in amphibians was established along with the development of an early life stage toxicity threshold for the frequency of teratogenic abnormalities in X. laevis. The bioenergetic and stress status in addition to the overall body condition of adult females after a 68 day dietary exposure showed no significant differences among treatment groups. The concentrations of Se measured in the ovary, egg, liver and muscle samples increased with female dietary Se levels with strong positive relationships between egg Se concentrations and the other three tissues being illustrated. Elevated in ovo Se exposure had no biologically significant effect on fertilization success, hatchability or mortality within the first 5 dpf; however, the frequency and severity of morphological abnormalities was significantly greater in tadpoles from the highest dose group, with eye lens abnormalities most prominently observed. Late stage larval survival and growth was unaffected by in ovo Se exposure; however, the distribution of developmental stages observed at the set time point when 50% of tadpoles completed metamorphosis showed a larger portion of tadpoles at earlier stages of development in the highest dose group despite no overall change in time to metamorphosis. The results of this thesis research in its entirety suggest that amphibians, as represented by X. laevis, are potentially more tolerant to elevated in ovo and dietary Se exposures than other oviparous vertebrates studied to date; however, without sufficient data for comparison it is unknown whether X. laevis is a tolerant, average or sensitive species among amphibians.

Selenium (Se) is an essential micronutrient, being a component of more than twenty seleno-proteins in humans. Previous studies suggested that increased intake of Se may reduce the risk of degenerative diseases including cancer; however, excessive intake can be toxic. Wheat is one of the major dietary sources of Se in humans, mainly in the form of L-selenomethionine (Se-met) but the impact of this source of Se on human health at the genome level was previously unexplored. This PhD project aimed to (a) determine the safe dose-range and bio-efficacy of Se-met in vitro; (b) identify the optimal concentration of Se-met for reduction of genome damage in vitro; (c) investigate the optimal concentration of Se-met for improving resistance to gamma radiation or hydrogen peroxide induced genome damage in vitro; d) determine the bioavailability and bioefficacy of Se in vivo, in the form of either Semet or wheat biofortified with Se; e) identify the nutrients and food groups that are correlated with Se intake/status and f) identify the nutrients, food groups and plasma mineral concentrations that are correlated to baseline lymphocyte DNA damage. The in vitro study was performed on the peripheral blood lymphocytes isolated from six males and cultured with media supplemented with Se-met in a series of Se concentrations from 3 to 3850 μg Se/l while keeping the total methionine (i.e. Se-met + L-methionine) concentration constant. Baseline genome stability of lymphocytes and the extent of DNA damage induced by 1.5 Gy γ-ray or 7.5 μM hydrogen peroxide (H₂O₂) were investigated using the Cytokinesis-block Micronucleus Cytome (CBMNCyt) assay and the alkaline Comet assay with and without glycosylase (Fpg or Endo III) treatment after 9 days of culture. Results showed that high Se concentrations (≥1880 μg Se/l) caused strong inhibition of cell division, extensive DNA damage and increased cell death indicating cytotoxicity and genotoxicity. Baseline frequency of nucleoplasmic bridges (NPBs) and nuclear buds (NBud) declined significantly as Se concentration increased from 3 μg Se/l to 430 μg Se/l (P trend = 0.03 and 0.008, respectively); however, a significant trend of increase in Comet DNA damage was also observed (P trend <0.05) in lymphocytes. Selenium concentration (≤ 430 μg Se/l) had no significant effect on baseline frequency of micronuclei (MN) or DNA oxidation and had no protective effect against γ-ray-induced or H₂O₂-induced genome damage in lymphocytes. A randomised double-blind placebo-controlled intervention trial was conducted on healthy South Australian males (n = 62, age (mean ± SD) 56 ± 7.0 years) with Se dosage increased every 8 weeks for a total duration of 24 weeks. This study compared the bioavailability, by using plasma Se concentration as the biomarker, and bioefficacy of Se, by using platelet glutathione peroxidase (GPx) activity and lymphocyte DNA damage as biomarkers, from wheat process-fortified with Se-met (PROFORT) and high-Se wheat biofortified with Se (BIOFORT) compared to non-fortified normal (CONTROL) wheat. It was found that increased Se intake from BIOFORT wheat increased plasma Se concentration effectively in a dose-response manner from a baseline of 122 μg/l up to 190 μg/l (P<0.001). Increased Se intake from PROFORT wheat also increased plasma Se with a plateau at 140 μg/l, being therefore less effective than BIOFORT wheat (P<0.001). There was no significant change in Se status in the CONTROL group. Improved plasma Se concentrations had no effect on platelet GPx activity or lymphocyte DNA damage in either of the intervention groups. Results from the food frequency questionnaire (FFQ) survey (n = 173) and plasma Se concentration survey (n = 179) suggested that the study population screened for participation in the in vivo trial described above had a mean plasma Se concentration (± SD) of 102 (± 12) μg/l and a mean (± SD) estimated Se intake of 165 (± 68) μg/d. This is a higher estimated Se intake than found in previous Australian studies. The major dietary sources of Se were found to be bread/cereals, fish/seafood and meat. However, increased intake of nuts/seeds, which are rich in Se, may have undesirable effects on lymphocyte DNA oxidation in this Se-replete population. In conclusion, the in vitro studies suggest that (1) Se-met at higher concentrations at greater or equal to 1880 μg Se/l is cytotoxic; (2) Se-met may improve specific genome stability biomarkers such as nucleoplasmic bridge and nuclear bud at concentrations up to 430 μg Se/l, but further studies are needed to verify this effect. The in vivo studies in older men showed that Se from BIOFORT wheat is more effective in raising plasma Se concentration than Se from wheat process-fortified by the addition of Se-met, when both wheat products were subjected to strong heat. However, the platelet GPx activity and lymphocyte DNA damage appeared not to be modified by improved Se status. This work contains two publications: 1) "The effect of selenium, as selenomethionine, on genome stability and cytotoxicity in human lymphocytes as measured by the cytokinesis-block micronucleus cytome assay". Mutagenesis 2009 May;24(3):225-32. 2) "Increased consumption of wheat biofortified with selenium does not modify biomarkers of cancer risk, oxidative stress or immune function in Australian males" Environmental Molecular Mutagenesis. 2009 July; 50 (6):489-501 The latter one was not able to be published in a journal of higher impact factor due to part of the data had been published elsewhere. Both articles are attached in Appendix.
http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1523459
Thesis (Ph.D.) -- University of Adelaide, School of Agriculture, Food and Wine, 2010

Omega-3 polyunsaturated fatty acids can reduce the risk of cardiovascular disease and cancers. Enriching broiler meat opportunities lack research on product quality. The fatty acid (FA) profile of birds fed flaxseed for various periods was analyzed. Another experiment assessed FA profile and oxidation products in frozen-raw and cooked thigh meat in birds fed 20% linPRO (50% extruded flaxseed) with antioxidant combinations. Males deposited more omega-3 in breast meat than females. It required 26.2 d (10%flax) or 11.3 d (17%flax) feeding to achieve the 300 mg omega-3/100g of breast. Eicosapentaenoic and docosahexaenoic acids were deposited in the phospholipids whereas a-linolenic acid associated with triacylglycerols. Oxysterol appearance was reduced in thighs of high vitamin E birds while the high selenium treatment had no effect or even raised oxysterols during roasting. Antioxidants inhibited thiobarbuturic reactive acid substances in stored frozen-raw meat. Stability of omega-3 broiler meat was improved with increased dietary antioxidant levels.
Food Science and Technology

Selenium (Se) is known to cause chronic toxicity in aquatic species. In particular, dietary exposure of fish to selenomethionine (SeMet), the primary form of Se in the diet, is of concern. Previous studies reported that chronic exposure to elevated dietary SeMet altered swimming performance, aerobic metabolism, and energy and endocrine homeostasis in adult fish. However, little is known about the direct effects of dietary SeMet exposure in juvenile fish. Therefore, the overall objective of this thesis was to investigate sublethal pathophysiological effects of subchronic dietary SeMet exposure in two juvenile fish species, fathead minnow (Pimephales promelas) and rainbow trout (Oncorhynchus mykiss). In the first experiment, 20 days post hatch (dph) juvenile fathead minnow were exposed to different measured concentrations (2.8, 5.4, 9.9, 26.5 µg Se/g dry mass [dm]) of Se in food in the form of SeMet for 60 days. In the second experiment, 14 dph juvenile rainbow trout were exposed for 37 days to different measured concentrations (1.0, 4.1, 11.2, 26.1 µg Se/g dm) of Se in food in the form of SeMet. Following exposure, samples were collected for Se analysis and fish were subjected to a swimming performance challenge to assess critical swim speed (Ucrit), tail beat frequency and tail beat amplitude, oxygen consumption (MO2), cost of transport (COT), standard metabolic rate (SMR), active metabolic rate (AMR), and factorial aerobic scope (F-AS). Dietary SeMet exposure impaired swimming ability in both fathead minnow and rainbow trout. Juvenile fathead minnow showed alterations in aerobic metabolism with increased MO2, COT and AMR at the 9.9 and 26.5 µg Se/g diets, while dietary SeMet exposure did not appear to affect aerobic metabolism in juvenile rainbow trout. After swim performance experiments, swam fish were considered fatigued and metabolic and energy storage endpoints were compared to non-swam (non-fatigued) fish. Energy storage capacity was measured via whole body (fathead minnow) and liver and muscle (rainbow trout) triglyceride and glycogen concentrations. For fathead minnow, triglyceride concentrations in non-swam fish were significantly elevated in the 5.4 µg Se/g group relative to controls, and swam fish had significantly lower whole body triglycerides than non-swam fish. All non-swam SeMet exposure groups had significantly decreased whole body glycogen concentrations compared to controls while the 5.4 and 26.5 µg Se/g exposure groups had significantly greater whole body glycogen concentrations in swam versus non-swam fish. In juvenile rainbow trout, liver triglyceride concentrations were significantly lower in all SeMet exposed groups compared to controls in non-swam fish. Swimming decreased liver and muscle triglycerides in the control and 11.2 µg Se/g treatment groups. Liver glycogen concentrations were greater in swam trout in the 4.1 µg Se/g dm exposure group. Muscle glycogen concentrations in non-swam fish, were significantly decreased in the 4.1 and 11.2 µg Se/g exposed groups compared to controls, while muscle glycogen in swam fish was unaffected by dietary SeMet exposure. For the swim status factor, muscle glycogen concentrations were significantly greater in swam versus non-swam trout in all treatment groups. Therefore, dietary SeMet exposure caused impaired swimming performance and metabolic alterations in both juvenile fathead minnow and juvenile rainbow trout. Species differences were apparent, especially in the patterns of altered energy status between swam and non-swam fish exposed to Se. Overall, the pathophysiological implications of these sublethal effects are unclear, but suggest that dietary SeMet exposure may negatively influence juvenile fish survivability in natural habitats.