Modification of chemical toxicity by selenium deficiency.
Selenium deficiency causes a number of hepatic metabolic alterations in the rat which could lead to changes in chemical toxicity. It causes a decrease in glutathione peroxidase activity, an increase in glutathione S-transferase activity, and an increase in the rate of glutathione synthesis. The hepatotoxicities of three compounds which bind to glutathione S-transferase; iodipamide, acetaminophen, and aflatoxin B1, are decreased by selenium deficiency. The toxicity of redox cycling compounds is generally increased by selenium deficiency and is accompanied by evidence of lipid peroxidation. Thus, nitrofurantoin (100 mg/kg) causes renal tubular necrosis in selenium-deficient rats but not in controls. Selenium-deficient rats are much more sensitive to diquat toxicity than are controls. Lethality of diquat in selenium-deficient rats appears to be causally linked to lipid peroxidation. Lethality of diquat in control rats is not linked to lipid peroxidation. The effect of selenium does not appear to be mediated by glutathione peroxidase, however, indicating that selenium has another oxidant defense function. Another interesting observation made was that increases in inspired O2 tension decreased ethane production (lipid peroxidation) in selenium-deficient and in control rats given diquat. Thus, O2 appears to prevent diquat-induced lipid peroxidation.
D000082:Acetaminophen / Q000633:toxicity; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity; D000818:Animals; D004178:Diquat / Q000633:toxicity; D064420:Drug-Related Side Effects and Adverse Reactions; D005982:Glutathione Transferase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009582:Nitrofurantoin / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology / Q000633:toxicity; D004364:Pharmaceutical Preparations / Q000378:metabolism; D051381:Rats; D012643:Selenium / Q000172:deficiency*
D000348:Aflatoxins; D008054:Lipid Peroxides; D004364:Pharmaceutical Preparations; D000082:Acetaminophen; D009582:Nitrofurantoin; D016604:Aflatoxin B1; D004178:Diquat; D005982:Glutathione Transferase; D012643:Selenium; D010100:Oxygen