ALLYL ALCOHOL CYTOTOXICITY IN ISOLATED RAT HEPATOCYTES - EFFECTS OF AZIDE, FASTING, AND FRUCTOSE

The role of altered energy homeostasis in the lethality of allyl alcoh ol to isolated rat hepatocytes was studied. ATP, ADP, AMP, and viabili ty loss (leakage of lactate dehydrogenase into the medium) were measur ed in isolated hepatocytes of fed or fasted rats exposed to 0.5 mM all yl alcohol. Adenine mononucleotides and cytotoxicity were determined a lso in hepatocytes incubated with allyl alcohol in the presence of 4 m M sodium azide or 15 mM fructose. Allyl alcohol-induced cell death in hepatocytes of fed rats was preceded by slight decreases in ATP conten t and energy charge (16% and 12%, respectively). More substantial decr eases in these parameters occurred in parallel with cell killing, but the effect of allyl alcohol on energy status did not exceed the effect produced by a nonlethal concentration of sodium azide. Neither azide nor fructose affected the development of allyl alcohol cytotoxicity. M oreover, allyl alcohol-induced cytotoxicity was similar in hepatocytes of fed and fasted rats. The results suggest that altered energy homeo stasis is a consequence rather than a cause of allyl alcohol-induced h epatocyte lethality.