Isolated hepatocytes as a model for aging effects on hepatotoxicity: studies with allyl alcohol.

The influence of aging on the toxicity of allyl alcohol was studied in hepatocytes isolated from male Fischer 344 rats. Initial values for trypan blue uptake, lactate dehydrogenase (LDH) release, alanine aminotransferase release, and glutathione content were similar in cells isolated from rats aged 5, 15, or 26 months. Incubation with 0.1 to 0.8 mM allyl alcohol resulted in a dose- and time-dependent loss of viability. Dose-effect and time-effect curves were displaced to the left with hepatocytes isolated from old rats compared with those from young rats. Intermediate values were found for hepatocytes of middle-aged rats. Inhibition by pyrazole of allyl alcohol-induced LDH release from hepatocytes also was affected by age. Total protection was observed for cells from young rats whereas no protection was found for those of old rats. Cells from middle-aged rats were between the extremes. The results demonstrate that isolated hepatocytes can be used to study age-related differences in hepatotoxicity.