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.