LIPID-PEROXIDATION, CYP2E1 AND ARACHIDONIC-ACID METABOLISM IN ALCOHOLIC LIVER-DISEASE IN RATS

The role of cytochrome P450 metabolism of fatty acids and lipid peroxi dation in the alterations of the fatty acid composition of the liver a nd liver pathology was investigated. The CYP2E1 inhibitors partially p revented CYP2E1 induction by ethanol and completely blocked lipid pero xidation. However, the liver pathology induced by ethanol was only par tially prevented as was the decrease in arachidonic acid in total live r lipid, triglycerides and cholesterol esters. This means that liver p eroxidation induced by ethanol can not completely account for the live r pathology or the decrease in arachidonic acid caused by ethanol. Lau ric acid omega-1 hydroxidation by the liver microsomes in vitro was in creased by ethanol and partially blocked by CYP2E1 inhibitors, However , although ethanol feeding increased the total hydroxidation and epoxi dation of arachidonic acid, these were not inhibited by CYP2E1 inhibit ors. Thus the ethanol-induced arachidonic acid depletion is not likely due to CYP2E1 metabolism of arachidonic acid, since the severity of l iver pathology correlated negatively with the decrease in arachidonic acid in the ethanol-fed rats. The increase in its metabolism by micros omes and decrease in synthesis may be an important mechanism of ethano l-induced liver injury.