Resveratrol, melatonin, vitamin E, and PBN protect against renal oxidative DNA damage induced by the kidney carcinogen KBrO3.
Free radical scavengers can protect against the genotoxicity induced by chemical carcinogens by decreasing oxidative damage. The protective effect of the antioxidants melatonin, resveratrol, vitamin E, butylated hydroxytoluene and 2-mercaptoethylamine, and the spin-trapping compound alpha-phenyl-N-tert-butyl nitrone (PBN) against oxidative DNA damage was studied in the kidney of rats treated with the kidney-specific carcinogen potassium bromate (KBrO3). KBrO3 was given to rats previously treated with melatonin, resveratrol, PBN, vitamin E, butylated hydroxytoluene, or 2-mercaptoethylamine. Oxidative damage to kidney DNA was estimated 6 hours afterwards by measuring 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxo8dG) referred to deoxyguanosine (dG) by means of high performance liquid chromatography with electrochemical-coulometric and ultraviolet detection. Levels of oxo8dG in the renal genomic DNA significantly increased by more than 100% after the KBrO3 treatment. This increase was completely abolished by the treatment with resveratrol and was partially prevented by melatonin, PBN and vitamin E. Resveratrol and PBN also prevented the increase in relative kidney weight induced by KBrO3. These results show that various different antioxidants and a free radical trap, working in either the water-soluble or the lipid-soluble compartments, can prevent the oxidative DNA damage induced in the kidney by the carcinogen KBrO3.
Cadenas
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Department of Animal Biology-II (Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain.
Barja
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G
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001959:Bromates / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003497:Cyclic N-Oxides; D004249:DNA Damage; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013113:Spin Labels; D013267:Stilbenes / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D001959:Bromates; D002273:Carcinogens; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D013113:Spin Labels; D013267:Stilbenes; C019536:potassium bromate; D014810:Vitamin E; C029217:phenyl-N-tert-butylnitrone; D008550:Melatonin; D000077185:Resveratrol