Use of Isolated Periportal and Perivenous Rat Hepatocytes for Studying the Acinar Heterogeneity of Xenobiotic Metabolism: Cytotoxicity of Allyl Alcohol

Abstract

The periportal hepatotoxicity of allyl alcohol (AlOH) was investigated by studying its metabolism and cytotoxicity in suspensions of periportal (pp) and perivenous (pv) rat hepatocytes isolated by digitonin-collagenase perfusion. No marked difference in alcohol dehydrogenase activity between the cell types was observed. The cells also oxidised AlOH at about equal rates. AlOH depleted cellular glutathione by about 95% within 10 minutes in both cell types, but was partially restored during subsequent incubation. The pp cells suffering from AlOH toxicity in vivo tended to resist AlOH in vitro better than pv hepatocytes, as judged from the measurement of cellular ATP and K+ ion content, and LDH leakage. It is suggested that the oxidation of AlOH may be restricted to the pp region in intact liver simply because of the high rate of uptake and oxidation of AlOH by the liver tissue.