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J Hepatol. 1998 Mar;28(3):410-6.

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.

Author information

1
Department of Gastroenterology, Catholic University of Louvain, Brussels, Belgium.

Abstract

BACKGROUND/AIM:

Fatty liver has been associated with an increased risk of primary graft non-function and drug toxicity. However, these effects have been observed mainly in fatty liver with inflammation, a situation characterized by an overall reduction in cytochrome P-450 (CYP)-dependent activities as well as a contrasting increase in CYP2E1 activity. Our aim was to examine the impact of liver-fat accumulation on CYP in two animal models of fatty liver without necroinflammation.

METHODS:

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) and chlorzoxazone hydroxylase (CZOHase) activities as well as CYP2E1 and CYP3A proteins were quantified on microsomal proteins.

RESULTS:

Livers from force-fed ducks exhibited significant decreases in total CYP, AND, END and CZOHase activities, inversely correlated with fat-liver content. Refeeding male Wistar rats a high-glucidic, fat-free diet after 48 h fasting, resulting in a 235% increased liver fat content, was associated with a decrease in total CYP (55%), AND (78%), END (55%) and CZOHase (62%) activities as well as in CYP3A (70%) and CYP2E1 (80%) protein 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 associated with a significant decrease in CYP activities and in CYP protein expression. Furthermore, the decreases in both CYP content and related activities were correlated with the degree of liver fat content.

PMID:
9551678
DOI:
10.1016/s0168-8278(98)80314-0
[Indexed for MEDLINE]

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