The Decisive Porlevels in Haloalkane-Mediated Liver Cell Injury

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Abstract
The model hepatotoxine carbon tetrachloride (CC14) was used to study haloalkane free radical-induced lipid peroxidation in isolated rat hepatocytes at steady state oxygen partial pressures (pO,) between 0.2 and IOOmmHg. Equilibrium oxygen conditions were achieved by using an oxystat system. Monitoring of hepatocellular oxygen uptake, malondialdehyde-formation and low-level chemilumine-scence during incubations of CC14-supplemented hepatocytes indicated a drastic stimulation of lipid peroxidation at p02-levels between 1 and lOmmHg. Above and below this pO2-region the potency of CC14 to induce lipid peroxidation sharply decreased. The evaluation of cellular damages by determining trypan blue exclusion and lactate dehydrogenase leakage revealed that in the presence of CC14 hepatocellular injury was significantly increased at those pO2-levels which were optimal for CC14-mediated lipid peroxidation. The present results demonstrate that CC14 is a potent inducer of lipid peroxidation also in the intact hepatocyte, provided that the p02 is maintained at distinct low levels. The coincidence of lipid peroxidation and loss of cell viability at the same pO,-range provides further evidence for the assumption that the haloalkane-mediated liver cell injury is due to a peroxidative process which primarily occurs at the hypoxic end of the physiological pO, -levels (1-70 mmHg) in liver.

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