REDUCTION IN HEPATIC CYTOCHROME-P-450 IS CORRELATED TO THE DEGREE OF LIVER FAT-CONTENT IN ANIMAL-MODELS OF STEATOSIS IN THE ABSENCE OF INFLAMMATION

Background/Aim: Fatty liver has been associated with an increased risk of primary graft non-function and drug toxicity. However, these effec ts have been observed mainly in fatty liver with inflammation, a situa tion characterized by an overall reduction in cytochrome P-450 (CYP)-d ependent activities as well as a contrasting increase in CYP2E1 activi ty. Our aim was to examine the impact of liver-fat accumulation on CYP in two animal models of fatty liver without necroinflammation. Method s: Ducks were force-fed with a high-glucidic diet and male Wistar rats , after 48 h fasting, were refed a high-glucidic, fat-free diet for 48 h. Total CYP, aminopyrine- (AND), erythromycin-N-demethylase (END) an d chlorzoxazone hydroxylase (CZOHase) activities as well as CYP2E1 and CYP3A proteins were quantified on microsomal proteins. Results: Liver s from force-fed ducks exhibited significant decreases in total CYP, A ND, END and CZOHase activities, inversely correlated with fat-liver co ntent. Refeeding male Wistar rats a high-glucidic, fat-free diet after 48 h fasting, resulting in a 235% increased liver fat content, was as sociated with a decrease in total CYP (55%), AND (78%), END (55%) and CZOHase (62%) activities as well as in CYP3A (70%) and CYP2E1 (80%) pr otein content. A significant inverse correlation was observed between CYP and total lipid content. Conclusions: In these models of steatosis induced by nutritional manipulations, fat liver accumulation was asso ciated with a significant decrease in CYP activities and in CYP protei n expression. Furthermore, the decreases In both CYP content and relat ed activities were correlated with the degree of liver fat content.