Relative contributions of protein sulfhydryl loss and lipid peroxidation to allyl alcohol-induced cytotoxicity in isolated rat hepatocytes.
The time course of allyl alcohol-induced toxicity was studied in freshly isolated rat hepatocytes. The sequence of events was as follows: an initial, rapid depletion of glutathione (GSH), a subsequent increase in malondialdehyde (MDA) and decrease in protein sulfhydryl groups (PSH), and the eventual loss of membrane integrity. The sulfhydryl compounds, N-acetylcysteine and dithiothreitol, markedly delayed the depletion of GSH, prevented significant loss of PSH, and protected the cells against viability loss. In contrast, the antioxidants, butylated hydroxytoluene and Trolox C, and the iron-chelating agent, deferoxamine, suppressed allyl alcohol-induced MDA production without affecting the depletion of cellular thiols or the loss of viability. The results suggest that the inactivation of protein thiol groups is critical for allyl alcohol toxicity whereas lipid peroxidation is not essential to the toxic process.
Hormann
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Department of Pharmacology, College of Medicine, University of Oklahoma, Health Sciences Center, Oklahoma City 73190.
Moore
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Rikans
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D000433:1-Propanol / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000032:analysis; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020005:Propanols; D011506:Proteins / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D013438:Sulfhydryl Compounds / Q000032:analysis*
D000975:Antioxidants; D020005:Propanols; D011506:Proteins; D013438:Sulfhydryl Compounds; C006463:allyl alcohol; D000433:1-Propanol; D005978:Glutathione; D003676:Deferoxamine