Dithiothreitol reversal of allyl alcohol cytotoxicity in isolated rat hepatocytes.
Reversal by dithiothreitol (DTT) of allyl alcohol cytotoxicity was investigated in isolated rat hepatocytes. Allyl alcohol-induced protein sulfhydryl loss, bleb formation, and cell death were prevented by DTT, when it was added to hepatocytes 30 min after the toxicant. The protective effect of DTT also was demonstrated in cells that were washed after 30 min of exposure to allyl alcohol, indicating that protection was not related to inhibition of allyl alcohol metabolism or inactivation of acrolein. DTT reversed the cell surface protrusions that formed during exposure to allyl alcohol, but reversal of blebbing did not insure that the cells would remain viable. Glutathione disulfide was not formed in allyl alcohol-treated cells, and DTT reversal of cytotoxicity occurred without restoring glutathione levels. Moreover, protection against allyl alcohol toxicity required the continuous presence of DTT. The results suggest that initial events in the toxic process are reversible, and that DTT can prevent cytotoxicity if added to hepatocytes before irreversible damage occurs; however, the mechanism by which DTT exerts its protection is not clear.
Rikans
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Department of Pharmacology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
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D000433:1-Propanol / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D004229:Dithiothreitol / Q000627:therapeutic use*; D004347:Drug Interactions; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D020005:Propanols; D011506:Proteins / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000502:physiology
D020005:Propanols; D011506:Proteins; D013438:Sulfhydryl Compounds; C006463:allyl alcohol; D000433:1-Propanol; D005978:Glutathione; D004229:Dithiothreitol; D019803:Glutathione Disulfide