DITHIOTHREITOL REVERSAL OF ALLYL ALCOHOL CYTOTOXICITY IN ISOLATED RATHEPATOCYTES

Reversal by dithiothreitol (DTT) of allyl alcohol cytotoxicity was inv estigated in isolated rat hepatocytes. Allyl alcohol-induced protein s ulfhydryl loss, bleb formation, and cell death were prevented by DTT, when it was added to hepatocytes 30 min after the toxicant. The protec tive effect of DTT also was demonstrated in cells that were washed aft er 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 du ring exposure to; allyl alcohol, but reversal of blebbing did not insu re that the cells would remain viable. Glutathione disulfide was not f ormed in allyl alcohol-treated cells, and DTT reversal of cytotoxicity occurred without restoring glutathione levels. Moreover, protection a gainst allyl alcohol toxicity required the continuous presence of DTT. The results suggest that initial events in the toxic process are reve rsible, 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.