FISH-OIL, ALCOHOL, AND LIVER PATHOLOGY - ROLE OF CYTOCHROME-P450 2E1

Rats were fed ethanol in combination with fish oil or a corn diet in o rder to evaluate the effect of fish oil feeding on liver injury, micro somal ethanol oxidation, and NADPH-dependent lipid peroxidation. The r ats were maintained on the dietary regimen for 72 days, and for compar ison, pair-fed controls were studied. The liver pathology score progre ssively worsened in rats fed alcohol, both in combination with fish oi l and corn oil, but the severity of inflammation and focal fibrosis wa s greater in the ethanol fish oil fed rats as compared with the ethano l corn oil group, whereas the fatty change was greater in the ethanol corn oil fed rats. The alcohol treatment caused a 5-fold increase of t he liver microsomal P450 content, and about a similar increase in the rate of microsomal NADPH oxidation. The amount of ethanol-inducible CY P2E1 was about 10-fold higher in alcohol-fed rats as compared with pai r-fed controls. The NADPH-dependent lipid peroxidation in liver micros omes was about 10-fold higher in microsomes from alcohol-treated rats fed corn oil as compared with controls, but only 2- to 3-fold higher i n alcohol-fed rats receiving fish oil than in pair-fed controls. This was due to a higher rate of NADPH-dependent lipid peroxidation in the control rats receiving fish oil. There was a pronounced correlation be tween the amount of CYP2E1 and the microsomal NADPH peroxidation in va riously treated rats, and between the 2E1 levels and the pathology sco re. The data suggest that fish oil diet, like corn oil, supports ethan ol-induced liver injury which is related to CYP2E1 induction and the p resence of polyunsaturated fatty acids in the diet (i.e., either n-6 o r n-3).