Hepatic Selenium Research Articles

RNA-Seq Analysis in Liver of Selenium-deficient Selenocysteine Lyase Knockout Mouse (P24-023-19)

ObjectivesSelenium is a trace element critical for appropriate response to oxidative stress in cells. Once ingested, dietary selenium is mostly metabolized by the liver. Selenium is utilized to produce the amino acid selenocysteine, which can be incorporated into selenoproteins, most of them functioning in curbing reactive oxygen species. The enzyme selenocysteine lyase (Scly) decomposes selenocysteine into selenide, and its highest expression and activity occurs in the liver. Disrupting the Scly gene (Scly−/−) resulted in overweight mice with hyperlipidemia, hyperinsulinemia and glucose intolerance, phenotype traits that were aggravated by a selenium-deficient diet. In the liver, Scly−/−mice had lower hepatic selenium levels than their wild-type mice counterparts. Our objective was to identify differentially expressed genes and pathways in Scly−/- mice livers affected by dietary selenium levels. MethodsScly−/- and wild-type mice were fed diets containing 0.08 (mildly low) or 0.25 (adequate) ppm of sodium selenite. We extracted total RNA from livers with a commercial kit. High-quality RNA (RIN ≥ 7) as assessed by a BioAnalyzer was employed in RNA-sequencing. RNA-Seq data analysis was performed on Partek flow software followed by pathway analysis using Ingenuity Pathway Analysis software. Validation of results was pursued by real-time RT-qPCR using specific primer sets. ResultsHepatic RNA-Seq analysis revealed 52 genes differentially regulated by Scly disruption and low dietary selenium levels, encompassing 41 pathways, including PXR/RXR activation, LPS/IL-1-mediated inhibition of RXR function, xenobiotic metabolism signaling, nicotine degradation, adipogenesis, and acyl-CoA hydrolysis. Ten differentially expressed genes were validated by real-time RT-qPCR, including Selenobp2, Eif4ebp3, Mt1, and Mt2. ConclusionsWe identified pathways and validated genes in the Scly−/- mouse liver that are implicated in the metabolic phenotype displayed by this model on a low selenium diet. Funding SourcesThis project was supported by the National Institutes of Health (NIH) grants U54MD007601 Ola Hawaii (subproject 5544), P30-CA071789–128, R01DK47320, and P20GM103466. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Ecotoxicoparasitology of mercury and trace elements in semi-aquatic mammals and their endoparasite communities

Many contaminants persist in the environment for decades or more, influencing ecosystem health. Environmental contamination with mercury (Hg) is a particular concern due to its ability to biomagnify in food webs and its lethal and sub-lethal effects in exposed organisms. Despite the known impacts of anthropogenic contamination, there remains a need for data on wildlife exposure to Hg and other contaminants, and the effects of exposure on wildlife health. The objectives of this study were to: 1) quantify differences in concentrations of mercury and other trace elements among three sympatric semiaquatic mammals of different assumed trophic position: North American river otter (Lontra canadensis), raccoon (Procyon lotor), and North American beaver (Castor canadensis), 2) compare trace element concentrations between animals captured on the Savannah River Site (SRS) in South Carolina, USA, where known inputs of Hg and other trace elements have occurred, and reference sites in South Carolina (SC) and Georgia (GA), USA, and 3) investigate the relationship between host trace element concentrations and endoparasite communities. River otters, beavers, and raccoons were sampled from the SRS, SC, and GA to quantify trace element concentrations in liver tissue and quantify endoparasite communities. Both species and sampling location were important factors determining hepatic trace element concentration, however, there was no consistent trend of elevated trace element concentrations among animals sampled on the SRS. Only Hg demonstrated biomagnification based on assumed trophic position, with river otters having the highest Hg concentrations among the sampled species. Additionally, the results suggest a possible relationship between host hepatic mercury concentration and endoparasite abundance, while hepatic selenium concentration may be related to endoparasite diversity. These findings further demonstrate how wildlife can accumulate anthropogenic contamination, although future research is needed to determine the mechanisms contributing to patterns observed between endoparasite communities and the contaminant concentrations of their mammalian hosts.

Hepatic ZIP8 deficiency is associated with disrupted selenium homeostasis, liver pathology, and tumor formation.

Zrt/Irt-like protein 8 (ZIP8) (encoded by Slc39a8) is a multifunctional membrane transporter that influxes essential metal cations Zn2+, Mn2+, Fe2+, and nonmetal inorganic selenite (HSeO3-). Physiological roles of ZIP8 in different cell types and tissues remain to be elucidated. We aimed to investigate ZIP8 functions in liver. Two mouse models were used in this study: 1) 13- to 21-mo-old Slc39a8(+/neo) hypomorphs having diminished ZIP8 levels and 2) a liver-specific ZIP8 acute knockdown mouse (Ad-shZip8). Histology, immunohistochemistry, and Western blotting were used to investigate ZIP8-deficiency effects on hepatic injury, inflammatory changes, and oxidative stress. Selenium (Se) and zinc (Zn) were quantified in tissues by inductively coupled plasma-mass spectrophotometry. We found that ZIP8 is required to maintain normal liver function; moderate or acute decreases in ZIP8 activity resulted in hepatic pathology. Spontaneous liver neoplastic nodules appeared in ~50% of Slc39a8(+/neo) between 13 and 21 mo of age, exhibiting features of inflammation, fibrosis, and liver injury. In Ad-shZip8 mice, significant hepatomegaly was observed; histology showed ZIP8 deficiency was associated with hepatocyte injury, inflammation, and proliferation. Significant decreases in Se, but not Zn, were found in Ad-shZip8 liver. Consistent with this Se deficit, liver expression of selenoproteins glutathione peroxidases 1 and 2 was downregulated, along with decreases in antioxidant superoxide dismutases 1 and 2, consistent with increased oxidative stress. Thus, ZIP8 plays an important role in maintaining normal hepatic function, likely through regulating Se homeostasis and redox balance. Hepatic ZIP8 deficiency is associated with liver pathology, including oxidative stress, inflammation, proliferation, and hepatocellular injury. NEW & NOTEWORTHY Zrt/Irt-like protein 8 (ZIP8) is a multifunctional membrane transporter that facilitates biometal and mineral uptake. The role of ZIP8 in liver physiology has not been previously investigated. Liu et al. discovered unique ZIP8 functions, i.e., regulation of hepatic selenium content and association of ZIP8 deficiency in mouse liver with liver defects.

Selenium Supplementation Alters Hepatic Energy and Fatty Acid Metabolism in Mice

Human and animal studies have raised concerns that supplemental selenium can increase the risk of metabolic disorders, but underlying mechanisms are unclear. We used an integrated transcriptome and metabolome analysis of liver to test for functional pathway and network responses to supplemental selenium in mice. Male mice (8-wk-old, C57BL/6J) fed a standard diet (0.41 ppm Se) were given selenium (Na2SeO4, 20 μmol/L) or vehicle (drinking water) for 16 wk. Livers were analyzed for selenium concentration, activity of selenoproteins, reduced glutathione (GSH) redox state, gene expression, and high-resolution metabolomics. Transcriptomic and nontargeted metabolomic data were analyzed with biostatistics, bioinformatics, pathway enrichment analysis, and combined transcriptome-metabolome-wide association study (TMWAS). Mice supplemented with selenium had greater body mass gain from baseline to 16 wk (55%±5%) compared with controls (40%±3%) (P<0.05); however, no difference was observed in liver selenium content, selenoenzyme transcripts, or enzyme activity. Selenium was higher in the heart, kidney, and urine of mice supplemented with selenium. Gene enrichment analysis showed that supplemental selenium altered pathways of lipid and energy metabolism. Integrated transcriptome and metabolome network analysis showed 2 major gene-metabolite clusters, 1 centered on the transcript for the bidirectional glucose transporter 2 (Glut2) and the other centered on the transcripts for carnitine-palmitoyl transferase 2 (Cpt2) and acetyl-CoA acyltransferase (Acaa1). Pathway analysis showed that highly associated metabolites (P<0.05) were enriched in fatty acid metabolism and bile acid biosynthesis, including acylcarnitines, triglycerides and glycerophospholipids, long-chain acyl-coenzyme As, phosphatidylcholines, and sterols. TMWAS of body weight gain confirmed changes in the same pathways. Supplemental selenium in mice alters hepatic fatty acid and energy metabolism and causes increases in body mass. A lack of effect on hepatic selenium content suggests that signaling involves an extrahepatic mechanism.

Hepatobiliary Quiz (Answers)—15 (2015)

Hepatobiliary Quiz (Answers)—15 (2015)

Mercury and selenium relationship in a tropical estuarine fish

Event Abstract Back to Event Mercury and selenium relationship in a tropical estuarine fish André Pinheiro Almeida1, Ana Carolina Pizzochero1 and Paulo Renato Dorneles1* 1 Federal University of Rio de Janeiro, Carlos Chagas Filho Biophysics Institute, Brazil Aquatic systems have been considered as final sinks for persistent and bioaccumulative toxicants (PBTs), such as metals and organohalogen compounds. Among the trace elements, non-essential metals deserve special attention due to their toxicity. In this context, mercury (Hg) should be highlighted due to its toxic effects, which comprise neurotoxicity, nephrotoxicity, hepatotoxicity, genotoxicity, among others. Several studies have highlighted the selenium-mediated methylmercury detoxification process, via mercury selenide formation in tissues of marine vertebrates. Despite being an essential element, selenium may also be toxic in high concentrations. This study focused on Guanabara Bay (GB), a heavily polluted urban estuary in Rio de Janeiro state (Brazil), where the whitemouth croaker (Micropogonias furnieri) provides a valuable fishery resource. Therefore, hepatic (Hg and Se) and muscular (Hg) concentrations of these elements were determined in GB whitemouth croakers. Mercury and selenium measurements were performed by cold vapor atomic absorption spectrometry (CV-AAS) and electrothermal AAS (ET-AAS), respectively. Total mercury (THg) concentrations in muscle (n=19) ranged from 184.9 to 858.6 (ng/g), while in liver they varied from 11.05 to 1188 (ng/g). Hepatic selenium concentrations ranged from 7820 to 40085 (ng/g). The hepatic Se:THg molar ratio ranged from 40,8 to 3102,5. The results showed a significant correlation between hepatic mercury and selenium levels, but the molar ratio suggests the absence of mercury selenide formation. Some of the Se concentrations found were above the threshold level for freshwater fish (12000 ng/g); however, it is not yet clear if these concentrations are toxic for marine fish as well. More studies are necessary for evaluating the impact of such exposure in fish from Guanabara Bay. Acknowledgements This study was supported by CNPq (National Research Council, Brazilian Ministry of Science and Technology) and FAPERJ (Rio de Janeiro state Research Support Foundation). Keywords: Whitemouth croaker, Micropogonias furnieri, Guanabara Bay, Tropical estuary, mercury selenide. Conference: XV European Congress of Ichthyology, Porto, Portugal, 7 Sep - 11 Sep, 2015. Presentation Type: Poster Presentation Topic: Physiology, Behavior and Toxicology Citation: Almeida A, Pizzochero A and Dorneles P (2015). Mercury and selenium relationship in a tropical estuarine fish. Front. Mar. Sci. Conference Abstract: XV European Congress of Ichthyology. doi: 10.3389/conf.FMARS.2015.03.00146 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Nov 2015; Published Online: 27 Nov 2015. * Correspondence: PhD. Paulo Renato Dorneles, Federal University of Rio de Janeiro, Carlos Chagas Filho Biophysics Institute, Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil, dornelespr@biof.ufrj.br Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers André Pinheiro Almeida Ana Carolina Pizzochero Paulo Renato Dorneles Google André Pinheiro Almeida Ana Carolina Pizzochero Paulo Renato Dorneles Google Scholar André Pinheiro Almeida Ana Carolina Pizzochero Paulo Renato Dorneles PubMed André Pinheiro Almeida Ana Carolina Pizzochero Paulo Renato Dorneles Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Protonation of Epigallocatechin-3-gallate (EGCG) Results in Massive Aggregation and Reduced Oral Bioavailability of EGCG-Dispersed Selenium Nanoparticles

The current results show that epigallocatechin-3-gallate (EGCG), in the form of phenolic anions at pH 8.0, can effectively disperse selenium nanoparticles. However, at gastric juice pH (1.0), the EGCG-dispersed selenium nanoparticles (referred to as E-Se) extensively aggregated, so that nano features largely disappeared. This demonstrates that deprotonated phenolic anions of EGCG play an important role in maintaining E-Se stability and suggests that E-Se would suffer from reduced oral bioavailability. To validate this conjecture, size-equivalent E-Se and bovine serum albumin (BSA)-dispersed selenium nanoparticles (B-Se), whose physicochemical properties were not altered at pH 1.0, were orally administered to selenium-deficient mice. In comparison to B-Se, the bioavailabilities of E-Se as indicated with hepatic and renal glutathione peroxidase activity and hepatic selenium levels were significantly (p < 0.01) reduced by 39, 32, and 31%, respectively. Therefore, the present study reveals that size-equivalent selenium nanoparticles prepared by different dispersers do not necessarily guarantee equivalent oral bioavailability.

Dietary antioxidants (selenium and N-acetylcysteine) modulate paraoxonase 1 (PON1) in PCB 126-exposed rats.

Environmental pollutants polychlorinated biphenyls (PCBs), especially dioxin-like PCBs, cause oxidative stress and associated toxic effects, including cancer and possibly atherosclerosis. We previously reported that PCB 126, the most potent dioxin-like PCB congener, not only decreases antioxidants such as hepatic selenium (Se), Se-dependent glutathione peroxidase, and glutathione (GSH) but also increases levels of the antiatherosclerosis enzyme paraoxonase 1 (PON1) in liver and serum. To probe the interconnection of these three antioxidant systems, Se, GSH, and PON1, we examined the influence of varying levels of dietary Se and N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS) and precursor for GSH synthesis, on PON1 in the absence and presence of PCB 126 exposure. Male Sprague-Dawley rats, fed diets with differing Se levels (0.02, 0.2, or 2 ppm) or NAC (1%), were treated with a single intraperitoneal injection of corn oil or various doses of PCB 126 and euthanized 2 weeks later. PCB 126 significantly increased liver PON1 mRNA, protein level and activity, and serum PON1 activity in all dietary groups but did not consistently increase thiobarbituric acid levels (thiobarbituric acid reactive substances, TBARS), an indicator of lipid oxidation and oxidative stress, in liver or serum. Inadequate (high or low) dietary Se decreased baseline and PCB 126-induced aryl hydrocarbon receptor (AhR) expression but further increased PCB 126-induced cytochrome P450 1A1 (CYP1A1) expression, the enzyme believed to be the cause for PCB 126-induced oxidative stress. In addition, a significant inverse relationship was observed not only between dietary Se levels and PON1 mRNA and PON1 activity but also with TBARS levels in the liver, suggesting significant antioxidant protection from dietary Se. NAC lowered serum baseline TBARS levels in controls and increased serum PON1 activity but lowered liver PON1 activities in animals treated with 1 μmol/kg PCB 126, suggesting antioxidant activity by NAC primarily in serum. These results also show an unexpected predominantly inverse relationship between Se or NAC and PON1 during control and PCB 126 exposure conditions. These interactions should be further explored in the development of dietary protection regimens.

Does Dietary Copper Supplementation Enhance or Diminish PCB126 Toxicity in the Rodent Liver?

Copper is essential for the function of the mitochondrial electron transport chain and several antioxidant proteins. However, in its free form copper can participate in Fenton-like reactions that produce reactive hydroxyl radicals. Aryl-hydrocarbon receptor (AhR) agonists, including the most potent polychlorinated biphenyl (PCB) congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), increase copper levels in rodent livers. This is accompanied by biochemical and toxic changes. To assess the involvement of copper in PCB toxicity, male Sprague-Dawley rats were fed an AIN-93G diet with differing dietary copper levels: low (2 ppm), adequate (6 ppm), and high (10 ppm). After three weeks, rats from each group were given a single ip injection of corn oil (control), 1, or 5 μmol/kg body weight PCB126. Two weeks following injections, biochemical and morphological markers of hepatic toxicity, trace metal status, and hepatic gene expression of metalloproteins were evaluated. Increasing dietary copper was associated with elevated tissue levels of copper and ceruloplasmin. In the livers of PCB126-treated rats, the hallmark signs of AhR activation were present, including increased cytochrome P450 and lipid levels and decreased glutathione. In addition, a doubling of hepatic copper levels was seen, and overall metal homeostasis was disturbed, resulting in decreased hepatic selenium, manganese, zinc, and iron. Expression of key metalloproteins was either decreased (cytochrome c oxidase), unchanged (ceruloplasmin and CuZnSOD), or increased (tyrosinase and metallothioneins 1 and 2) with exposure to PCB126. Increases in metallothionein may contribute/reflect the increased copper seen. Alterations in dietary copper did not amplify or abrogate the hepatic toxicity of PCB126. PCB126 toxicity, i.e., oxidative stress and steatosis, is clearly associated with disturbed metal homeostasis. Understanding the mechanisms of this disturbance may provide tools to prevent liver toxicity by other AhR agonists.

Vitamin E and Selenium Levels are Within Normal Range in Pigs Diagnosed with Mulberry Heart Disease and Evidence for Viral Involvement in the Syndrome is Lacking

SummaryMulberry heart disease (MHD) in pigs is characterized by lesions of acute haemorrhagic myocarditis and myocardial necrosis. The objectives of this study were to determine the levels of vitamin E and selenium and 13 other trace minerals in heart and liver tissues and to determine the prevalence of certain viral infections in heart tissues from MHD‐affected and MHD‐unaffected pigs and the vitamin E and selenium concentration in feed samples from selected farms with MHD. Based on the pathological examination, 114 pigs were separated into MHD lesion‐negative (L‐NEG) (n = 57) and MHD lesion‐positive (L‐POS) (n = 57) groups. Seventy‐three samples (40 L‐NEG and 33 L‐POS) were subjected to chemical analysis, and 66 (32 L‐NEG and 34 L‐POS) were subjected to PCR detection for viral pathogens. Lower (P < 0.05) levels of myocardial copper, lower (P < 0.05) levels of hepatic magnesium and higher (P < 0.05) levels of myocardial and hepatic sodium were detected in the L‐POS cases. Although lower (P < 0.05) levels of hepatic selenium were detected in L‐POS group, all were within the normal range. Analysis of feed samples (n = 22) revealed that selenium levels in all the samples were above the legal limit (0.3 ppm) for pigs. Vitamin E levels in all feed samples were above 20 IU/kg. Among the 66 pigs subjected to PCR detection, there were 19, 4, 13, 8, 2 and 1 animals positive for porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, pan‐herpes virus, porcine enterovirus, pan‐pestivirus and porcine parvovirus, respectively. Clear evidence of viral association with L‐POS was lacking.

Glutathione Peroxidase (GSHPx) Activity in the Liver of Red Deer in Relation to Hepatic Selenium Concentrations, Sex, Body Weight and Season of the Year

The purpose of this study was to determine glutathione peroxidase (GSHPx) activity in the liver of red deer in relation to selenium concentrations in the liver, as well as to evaluate changes in GSHPx activity according to sex, body weight and season of the year. Total selenium concentration in the liver of red deer averaged 0.095 ± 0.018μg/g of wet weight. GSHPx activity in the liver of red deer ranged widely from 4.4 to 45.8U/g of protein. Females were characterized by higher GSHPx activity compared to males (21.2 vs. 17.0U/g protein). The highest GSHPx activity was recorded in autumn and the lowest in summer. The lowest GSHPx activity in the liver was found in the heaviest animals (>100kg body weight), averaging 14.0U/g protein. Animals weighing <66kg and 66-100kg were characterized by similar activity of 25.1 and 24.5U/g, respectively. Despite the differences in GSHPx activity according to sex, body weight and season of the year, these factors had no significant effect on the activity of this enzyme. The main factor regulating GSHPx activity in the liver of examined red deer was selenium concentration.

Supplemental Selenium Alleviates the Toxic Effects of Excessive Iodine on Thyroid

As excessive iodine intake is associated with a decrease of the activities of selenocysteine-containing enzymes, supplemental selenium was hypothesized to alleviate the toxic effects of excessive iodine. In order to verify this hypothesis, Balb/C mice were tested by giving tap water with or without potassium iodate and/or sodium selenite for 16weeks, and the levels of iodine in urine and thyroid, the hepatic selenium level, the activities of glutathione peroxidase (GSHPx), type 1 deiodinase (D1), and thyroid peroxidase (TPO) were assayed. It had been observed in excessive iodine group that hepatic selenium, the activities of GSHPx, D1, and TPO decreased, while in the groups of 0.2mg/L, 0.3mg/L and 0.4mg/L supplemental selenium, the urinary iodine increased significantly. Compared with the group of excessive iodine intake alone, supplemental selenium groups had higher activities of GSHPx, D1, and TPO. We could draw the conclusion that supplemental selenium could alleviate toxic effect of excessive iodine on thyroid. The optimal dosage of selenium ranges from 0.2 to 0.3mg/L which can protect against thyroid hormone dysfunction induced by excessive iodine intake.

HEPATIC MINERAL VALUES OF WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) FROM VIRGINIA

There is a lack of information on mineral requirements of free-ranging white-tailed deer (Odocoileus virginianus). In addition, mineral deficiencies or excesses may play a role in the development of parasitism/malnutrition syndrome. We measured hepatic mineral values in apparently healthy white-tailed deer from two sites in Virginia, USA, as well as in deer with presumptive parasitism/malnutrition syndrome during 2005-2007. Deer with presumptive parasitism/malnutrition syndrome that were displaying signs of emaciation and chronic diarrhea had significantly higher mean hepatic levels of magnesium (Mg) and zinc (Zn) compared with healthy deer. Healthy deer in our study from northern Virginia, USA (i.e., Fairfax, Fauquier, Loudoun, and Prince William counties) had significantly lower mean hepatic selenium (Se) levels compared with deer from Nottoway County, Virginia, USA, which is 200 km distant. Healthy deer from northern Virginia, USA, also had significantly lower mean hepatic cobalt (Co), copper (Cu), and molybdenum (Mo) levels. Adult deer had significantly higher mean levels of hepatic iron (Fe) compared with fawns. In addition, male deer had significantly higher mean hepatic Co levels compared with female deer. The significantly higher mean (+/-SD) level of Zn in sick deer from northern Virginia, USA (78.7+/-54.9 microg/g versus 35.8+/-7.4 microg/g in healthy deer) is potentially clinically significant, although no signs consistent with Zn poisoning were observed. All deer in our study from northern Virginia, USA, had marginal or deficient levels of Cu (mean+/-SD=27.4+/-18.3 microg/g) and Se (mean=0.08+/-0.03 microg/g), which may be predisposing this population to the development of parasitism/malnutrition syndrome.

Trace elements in different species of cetacean from Rio de Janeiro coast

The present work tested whether ecological and biological parameters have an influence on the accumulation of trace elements (As, Cd, Cu, Pb, Se and Ag) by the liver of three cetaceans species: two species of coastal habit (Pontoporia blainvillei and Sotalia guianensis) and one of oceanic habit (Stenella frontalis), that were incidentally caught in fishing nets along the north of Rio de Janeiro coast. Inter-species difference was observed on the accumulation of Cd and Pb (5.12 ± 0.74 µg g-1 and 21.25 ± 1.35 µg g-1, respectively). However, the three cetacean species, S. guianensis, P. blainvillei and S. frontalis presented similar hepatic concentrations of As, Cu and Ag. No gender differences were found on the bioaccumulation of trace elements. Hepatic trace element accumulation was influenced by body length, according to the cetacean species. S. guianensis, which co-habits the same coastal marine environment that P. blainvillei species, presented a significant difference between hepatic selenium concentration (20.70 ± 32.22 µg g-1 and 3.24 ± 2.02 µg g-1, respectively). Based on these results, it is possible to conclude that, not only the different environmental conditions, but also total length and mainly the feeding habit influenced the accumulation of trace elements by the liver of these cetacean species.

Sodium selenite enhances glutathione peroxidase activity and DNA strand breaks in hepatoma induced by N-nitrosodiethylamine and promoted by phenobarbital

An element/compound that acts as an antioxidant as well as, can increase the oxidative stress offers a new approach in differentiation therapy. Experiments were carried out to determine the effect of selenite on DNA damage and glutathione peroxidase (GPx) activity in N-nitrosodiethylamine (DEN) induced, phenobarbital promoted rat hepatoma. Supra-nutritional level of selenite (4 ppm) was supplemented at either, before-initiation/after-initiation and/or during entire period of the study. At the end of experiment period (20 weeks), extent of DNA damage (alkaline comet assay), selenium concentration, and GPx activity were assessed on nodular tissue (NL) cells, surrounding liver (SL) cells, and whole liver tissue (control) cells. Hepatic selenium level and GPx activity were decreased in DEN and PB-administered animals, whereas the DNA damage was found to be increased in both NL and SL cells compared with control group. However, the DNA damage is more in SL cells than in NL cells. Pre-supplementation of selenite did not show any difference in DNA (strand breaks) damage, selenium, and GPx activity. Increased hepatic selenium concentration and GPx activity were observed in both NL and SL cells in post-supplementation and entire period of selenite supplemented animals compared to DEN + PB treated animals. However, DNA damage was increased in NL but decreased in SL cells. Supplementation of selenite alone for 16 or 20 weeks had shown increased DNA damage, selenium concentration, and GPx activity compared to normal control animals. In summary, cancer bearing animals increased DNA damage and decreased Se level and GPx activity in NL and SL cells and other organs in cancer bearing animals, supplementation of Se further provoked DNA damage (no change in pretreatment) in NL cells, however it decreased DNA damage SL cells and other organs (kidney, lungs, and spleen). On the other hand Se levels and GPx activity were increased in NL and SL cells and other organs of Se-supplemented rats (no difference in group 3 animals). These results demonstrate that, in addition to chemopreventive and chemotherapeutic role of selenite, it also prevents cellular DNA damage induced in cancerous condition.

Thioacetamide-induced cirrhosis in selenium-adequate mice displays rapid and persistent abnormity of hepatic selenoenzymes which are mute to selenium supplementation

Selenium reduction in cirrhosis is frequently reported. The known beneficial effect of selenium supplementation on cirrhosis is probably obtained from nutritionally selenium-deficient subjects. Whether selenium supplementation truly improves cirrhosis in general needs additional experimental investigation. Thioacetamide was used to induce cirrhosis in selenium-adequate and -deficient mice. Selenoenzyme activity and selenium content were measured and the influence of selenium supplementation was evaluated. In Se-adequate mice, thioacetamide-mediated rapid onset of hepatic oxidative stress resulted in an increase in thioredoxin reductase activity and a decrease in both glutathione peroxidase activity and selenium content. The inverse activity of selenoenzymes (i.e. TrxR activity goes up and GPx activity goes down) was persistent and mute to selenium supplementation during the progress of cirrhosis; accordingly, cirrhosis was not improved by selenium supplementation in any period. On the other hand, selenium supplementation to selenium-deficient mice always more efficiently increased hepatic glutathione peroxidase activity and selenium content compared with those treated with thioacetamide, indicating that thioacetamide impairs the liver bioavailability of selenium. Although thioacetamide profoundly affects hepatic selenium status in selenium-adequate mice, selenium supplementation does not modify the changes. Selenium supplementation to cirrhotic subjects with a background of nutritional selenium deficiency can improve selenium status but cannot restore hepatic glutathione peroxidase and selenium to normal levels.

Chemopreventive activity of selenocysteine prodrugs against tobacco‐derived nitrosamine (NNK) induced lung tumors in the A/J mouse

Prodrugs of L-selenocysteine have potential utility in cancer chemoprevention. This study reports the efficacy of three selenazolidine-4(R)-carboxylic acids, (2-unsubstituted, 2-oxo, and 2-methyl derivatives; SCA, OSCA, and MSCA, respectively) against tobacco-related lung tumorigenesis in a mouse model. Seven days after initiation of an AIN-76A diet supplemented with sodium selenite (5 ppm Se), L-selenomethionine (3.75 ppm Se), Se-methyl-L-selenocysteine (3 ppm Se), L-selenocystine (15 ppm Se), SCA (15 ppm Se), OSCA (15 ppm Se), or MSCA (15 ppm Se), mice received 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 10 micromol, i.p.). After an additional 16 weeks on the diets, two compounds, OSCA and selenocystine, significantly reduced lung adenoma multiplicity from 7.2 tumors per mouse in the NNK group to 4.5 and 4.6 tumors per mouse, respectively. Neither selenium concentration nor glutathione peroxidase activity in either RBCs or liver served as surrogate indicators of tumor reduction. Hepatic selenium levels were significantly elevated by all selenium-containing compounds except Se-methyl-L-selenocysteine and SCA; RBC selenium levels by all except sodium selenite and MSCA. With the exception of L-selenomethionine, RBC glutathione peroxidase activity was increased along with the elevated selenium levels. Hepatic glutathione peroxidase activity was elevated by all Se-compounds except SCA. The two compounds showing significant tumor reduction (OSCA and selenocystine) were the only two compounds that showed ubiquity of changes, elevating both selenium levels and GPx activity in both liver and RBC.

Hepatic and renal tissue selenium levels in a mouse model of candidiasis

Hepatic and renal tissue selenium levels in a mouse model of candidiasis

Mercury and Selenium in Livers of Waterfowl Harvested in Northern Canada

Total mercury and selenium were measured in livers of green-winged teal, northern pintails, buffleheads, king eiders, Barrow's and common goldeneyes, surf and white-winged scoters collected from 12 sites across northern Canada between 1988 and 1994. Hepatic mercury concentrations were <1.0 mg x kg(-1) ww in 80% of the birds analyzed. Mercury levels did not vary much among species, with green-winged teal, northern pintails, and white-winged scoters, in particular, generally having quite low levels (<0.5 mg x kg(-1) ww). Northern pintails had the lowest Se concentrations (<2.5 mg x kg(-1) ww) overall whereas the higher Se concentrations (10-20 mg x kg(-1) ww) were found in the king eiders and scoters. Selenium showed a much greater variation in concentrations, particularly in the king eiders and scoters. Hepatic mercury concentrations found in the waterfowl analyzed in this study were an order of magnitude lower than toxicological threshold levels found in the literature. However, hepatic selenium concentrations in 33% of the females exceeded 3.0 mg x kg(-1) ww and some king eiders as well as some surf and white-winged scoters contained hepatic selenium concentrations >10 mg x kg(-1) ww suggesting levels of potential concern.

Temporal and geographic trends in trace element concentrations in moose from Yukon, Canada

The Yukon Contaminants Committee has conducted a hunter survey since 1994, annually requesting tissue samples from successful moose hunters in the Yukon. Moose kidney, liver and muscle tissue were analyzed for arsenic, cadmium, chromium, cobalt, copper, lead, mercury, molybdenum, selenium and zinc. Levels of most trace elements measured were not of concern toxicologically or in terms of deficiencies. Although hepatic selenium concentrations in Yukon moose were high compared to moose from other locations, and to domestic cattle, no indications of selenium toxicity have been observed. Renal and hepatic concentrations of cadmium in Yukon moose were also high when compared with moose from other locations. Results from this study suggest that 1) some moose in this area may be suffering from sublethal effects of Cd toxicity, 2) moose in this area may have evolved a high level of natural cadmium tolerance, 3) moose in this area may have developed a high level of cadmium tolerance over their lifetimes, or 4) moose, as a species, have a high level of Cd tolerance. Health Canada has recommended limiting consumption of Yukon moose kidneys and livers to one/year/person. Cadmium concentrations were positively correlated with age in moose kidneys, while arsenic, copper, molybdenum and selenium showed a negative correlation. Renal chromium and zinc showed an increasing trend from 1994–2001, while copper showed a decreasing trend, although in all three cases the r-values and the changes over time were low. None of the other elements tested exhibited a significant change over time. Analysis of moose renal element concentrations with stream sediment element concentrations was carried out on an ecoregion basis, a game management zone basis and a moose home range basis. Results suggest that, at least to some degree, renal element concentrations in moose are affected by the geology of their environment, particularly for cadmium, arsenic and lead. The results of these analyses are consistent with the hypothesis that the high levels of cadmium found in Yukon moose are coming from naturally occurring geological sources, likely via hyperaccumulating plants such as willows.