Protective effects of antioxidants against benomyl-induced lipid peroxidation and glutathione depletion in rats.
The present in vivo study was designed to examine the effects of the antioxidants, N,N-diphenyl-p-phenylenediamine (DPPD) and a 21-aminosteroid (U74389G), on methyl 1-(butylcarbamoyl)-2-benzimidazole-carbamate (benomyl)-induced lipid peroxidation and glutathione depletion in rats. Male Sprague Dawley rats weighing 200 250 g were used in this study and were fasted for 8 12 h before treatment. Benomyl (200 mg/kg/day in olive oil) was administered orally for 7 days to groups of untreated rats and to rats pretreated with two doses (15 mg/kg) of either DPPD or U74389G. Benomyl treatment resulted in a significant increase in serum hydroperoxides and a significant decline in hepatic reduced glutathione (GSH) levels. These results indicate that benomyl induces lipid peroxidation and glutathione depletion in rats. Benomyl-induced lipid peroxidation was blocked by DPPD pretreatment but was not significantly altered by U74389G. However, both antioxidants, DPPD and U74389G, were able to inhibit glutathione depletion induced by benomyl. The present findings indicate that the in vivo toxicity of benomyl may be associated with oxidative stress to cellular membranes and that some degree of protection against this toxicity could be afforded by antioxidants.
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College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee 32307, USA.
Soliman
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MR
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001542:Benomyl / Q000633:toxicity*; D004347:Drug Interactions; D005659:Fungicides, Industrial / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010545:Peroxides / Q000097:blood; D010655:Phenylenediamines / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D005659:Fungicides, Industrial; D010545:Peroxides; D010655:Phenylenediamines; D011281:Pregnatrienes; C074965:U 74389F; C004845:N,N'-diphenyl-4-phenylenediamine; D005978:Glutathione; D001542:Benomyl