FATTY-ACID OMEGA-HYDROXYLATION AND (OMEGA-1)-HYDROXYLATION IN EXPERIMENTAL ALCOHOLIC LIVER-DISEASE - RELATIONSHIP TO DIFFERENT DIETARY FATTY-ACIDS

Arachidonic acid concentrations in liver are decreased in response to ethanol administration. In addition, the oxygenated products of arachi donic acid metabolites could affect the severity of alcoholic liver in jury. Selective utilization of arachidonic acid by the cytochrome P-45 0 system could, in part, account for the decrease in arachidonic acid. To evaluate this pathway further, male Wistar rats were fed different dietary fats: medium chain triglycerides, palm oil, and corn oil or f ish oil with either ethanol or isocaloric amounts of dextrose. Histopa thology, cytochrome P-4502E1 (CYP2E1) and cytochrome P-4504A (CYP4A), and omega- and (omega-1)-hydroxylation products of lauric and arachido nic acids were evaluated. Ethanol induction of CYP2E1 was related to t he concentration of polyunsaturated fatty acids in the diet; induction of CYP4A by ethanol was seen in all groups. The highest levels of 11- hydroxy-lauric acid and 19-hydroxyarachidonic acid (omega-1) were seen in rats fed ethanol with palm oil and corn oil. Highly significant co rrelations were seen between the (omega-1)-hydroxylation products and CYP2E1 activity. No correlation was seen between the omega-hydroxylati on products and CYP2E1 activity. In contrast, the levels of w-hydroxyl ation products correlated with CYP4A. The overall results showed a sig nificant increase in (omega-1)-hydroxylation products in rats fed diet s containing significant amounts of linoleic acid (i.e., palm oil and corn oil).