Activity profile of glutathione-dependent enzymes and respiratory chain complexes in rats supplemented with antioxidants and treated with carcinogens.
Appropriate dietary interventions may reduce the potentially damaging effects of free radicals generated during metabolism and various physiological conditions. We have investigated the effects of dietary vitamins C, E, beta-carotene, or selenium (Se) on the activity of endogenous antioxidant enzymes and respiratory chain complexes in rats exposed to 7,12-dimethylbenz[a]anthracene (DMBA), a mammary carcinogen and bleomycin (BLM), an antineoplastic drug. These agents are known to generate DNA-reactive species during their metabolism, which may enhance oxidative stress in cells. Female Fischer 344 rats aged 4 months were given antioxidant supplements singly or as a mixture 2 weeks prior to mutagen treatments; antioxidant supplementation continued for an additional 4 weeks. In rats treated with mutagens, the antioxidant intake lowered the activity of Se-dependent glutathione peroxidase (Se-GPx) in liver cytosolic and mitochondrial fractions, compared to activity in rats treated with mutagens alone. However, the vitamins, but not Se supplement, persistently increased Se-GPx activity in untreated control animals. Treatment of animals with mutagen raised K(m) value of Se-GPx and this correlated with an increase in V(max). However, Se intake, either singly or mixture, significantly reduced K(m) value in mutagen-treated and untreated rats in both fractions. Se intake increased glutathione S-transferases (GST) activity (P < 0.05) in both liver fractions of mutagen-treated and untreated animals. Similar response was seen in Se-independent GPx. Since GST-alpha possesses Se-independent GPx activity, the enhanced effect observed in GST activity may be due, in part, to increased activity in Se-independent GPx. Also, selenium or the antioxidant vitamin supplementation increased the activity of all four respiratory chain complexes in untreated rats. Although BLM treatment significantly increased the activity of electron transport complexes III and IV, selenium or the vitamin supplements modulated the responses. These results indicate that the intake of dietary vitamins or Se enhances antioxidant capacity in chemically exposed animals compared to animals receiving antioxidants alone. Furthermore, in addition to being an enhancer of the catalytic function of glutathione peroxidase, selenium may directly play a role as an antioxidant.
Desai
V G
VG
Department of Health and Human Services, National Center for Toxicological Research, Jefferson, Arkansas 72079, USA. vdesai@nctr.fda.gov
Casciano
D
D
Feuers
R J
RJ
Aidoo
A
A
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage; D001761:Bleomycin / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D019587:Dietary Supplements; D004334:Drug Administration Schedule; D004579:Electron Transport / Q000187:drug effects*; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012643:Selenium / Q000008:administration & dosage; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage; D019207:beta Carotene / Q000008:administration & dosage
D000975:Antioxidants; D002273:Carcinogens; D009097:Multienzyme Complexes; D019207:beta Carotene; D001761:Bleomycin; D014810:Vitamin E; D015127:9,10-Dimethyl-1,2-benzanthracene; D010088:Oxidoreductases; D005979:Glutathione Peroxidase; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D005982:Glutathione Transferase; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D005978:Glutathione; D012643:Selenium; D001205:Ascorbic Acid