1-Methyl-4-phenylpyridinium has greater neurotoxic effect after selenium deficiency than after vitamin E deficiency in rat striatum.
The present study was designed to assess the extent of the protective effect of antioxidative capacity of dopaminergic neurons against the possible oxidative stress produced by 1-methyl-4-phenylpyridinium. We have studied the direct effect of 1-methyl-4-phenylpyridinium on striatum slices from rats fed with selenium-deficient or vitamin E-deficient diets for 30 days. Glutathione peroxidase activity decreased significantly after selenium dietary restriction. Our results showed that the effect of 1-methyl-4-phenylpyridinium on dopamine and its metabolites 3,4-dihydroxyphenylacetic acid, homovanillic homovanillic acid and 3-methoxytyramine in animals with both restriction diets was higher than in controls. However, this effect was significantly greater in animals with low selenium diets than with vitamin E-deficient diets in terms of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid, which were all significantly more depleted by 1-methyl-4-phenylpyridinium in selenium-deficient rats than in vitamin E-deficient rats. Therefore, considering changes in the levels of dopamine and its metabolites as an index of 1-methyl-4-phenylpyridinium toxicity, our results seem to indicate that the glutathione-glutathione peroxidase system has a greater protector effect than vitamin E.
Departamento de Bioquimica, Bromatologia y Toxicologia, Facultad de Farmacia, Sevilla, Spain.
M L
ML
Vizuete
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V
Steffen
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A
Machado
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J
Cano
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000502:physiology; D004435:Eating / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D020267:MPTP Poisoning; D008297:Male; D017072:Neostriatum / Q000201:enzymology / Q000473:pathology*; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000172:deficiency*; D014811:Vitamin E Deficiency / Q000473:pathology*
D005609:Free Radicals; D015102:3,4-Dihydroxyphenylacetic Acid; D005979:Glutathione Peroxidase; D012643:Selenium; C001746:3-methoxytyramine; D004298:Dopamine; D006719:Homovanillic Acid