Peroxidation of Mitochondrial Lipids of Rat Liver Following Chronic and Acute Alcohol Treatment

Abstract

Liver mitochondria were isolated from normal or alcohol treated rats. Their susceptibility to lipid peroxidation (LPO) on Fe-ADP addition was studied by following malondialdehyde production. Chronic alcohol dosing (3 weeks) resulted in a decreased LPO (initial rates less than half). In vitro additions of ethanol to normal mitochondria enhanced LPO, almost doubling initial rates at 2 ‰, whereas mitochondria from chronically treated animals showed little effect. Furthermore, chronic treatment decreased mitochondrial coupling as measured by the acceptor control ratio (ACR). In vitro additions had no effect. On alcohol treatment, the decreases in LPO and ACR showed individual, but parallel variations; for a given substrate, a close correlation of both parameters could be shown. Since the ACR reflects the maximum capability of a mitochondrial preparation for membrane energization brought about by charge separation due to respiration, we studied the effects of respiratory inhibitors and effectors of the surface charge density of the membrane. Respiratory inhibition by antimycin A or KCN almost halved LPO. Atractyloside or bromosulfophthalein which increased the negative surface charge by binding to the mitochondrial membrane enhanced LPO. LPO in mitochondria from chronically treated animals — though at lower levels — was affected analogously. The dependence of LPO on the energizeability of the mitochondrial membrane can also be demonstrated by titration with an uncoupler resulting in a decrease in ACR by successive increases in the proton permeability of the membrane and, consequently, decreased energizeability. Again, decreases in ACR and LPO were correlated.