PMID: 9551678Apr 29, 1998Paper

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

Journal of Hepatology
Isabelle LeclercqA P Geubel

Abstract

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. 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. 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 sign...Continue Reading

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Citations

Feb 19, 2000·Biochemical and Biophysical Research Communications·I A LeclercqG R Robertson
May 23, 2006·Pharmaceutical Research·Kouichi YoshinariMasao Miwa
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