Effects of low selenium diets on antioxidant status and MPTP toxicity in mice.
To investigate the role of chronic oxidative stress in MPTP neurotoxicity, C57BL mice were maintained 6-8 weeks on diets deficient in nutrients essential to cellular antioxidant defenses, selenium (Se) and alpha-tocopherol (vit E), and the effects on tissue antioxidant status and MPTP toxicity were evaluated relative to controls on supplemented diets. Activities of the major antioxidant enzymes, glutathione peroxidase (GPx), catalase, and superoxide dismutase, and levels of malondialdehyde as a marker for oxidative stress, were measured in brain, lung, liver and blood. Caudate depletion of dopamine and its metabolites served as a measure of MPTP neurotoxicity. For mice on the Se deficient diet, levels of the selenoenzyme GPx decreased from 50% in brain to 90% in blood. No compensatory changes in the activities of the other antioxidant enzymes were observed and addition of vit E to the diet did not alter antioxidant enzyme activities or malondialdehyde levels. In animals not treated with MPTP, the Se deficient diet significantly increased malondialdehyde only in liver. No protective effect of the antioxidant supplements against caudate depletion of dopamine and its metabolites were observed. However, malondialdehyde levels were increased in the brains of MPTP treated mice on the low Se diets, suggesting the possibility of secondary oxidative damage to tissues accompanying the destruction of substantia nigra neurons by MPTP.
Sutphin
M S
MS
Division of Nutritional Sciences, UCLA School of Public Health 90024.
Buckman
T D
TD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002374:Catalase / Q000097:blood / Q000378:metabolism; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004032:Diet; D004298:Dopamine / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D020267:MPTP Poisoning; D008297:Male; D008315:Malondialdehyde; D051379:Mice; D008810:Mice, Inbred C57BL; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency*; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism; D014811:Vitamin E Deficiency / Q000378:metabolism
D000975:Antioxidants; D008315:Malondialdehyde; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D012643:Selenium; D004298:Dopamine