Alterations in drug metabolizing activities in acute hepatosteatosis induced by intake of a high-carbohydrate/fat-free diet after food deprivation
DOI:
https://doi.org/10.31989/ffhd.v6i1.238Abstract
ABSTRACT
Background: Lipid accumulation in hepatocytes constitutes a major component in the pathogenesis of chronic liver injury. However, the impact of lipid deposition in liver on drug metabolizing capacity remains unclear.
Purpose of the study: The present study was undertaken to evaluate the changes in hepatic cytochrome P-450 (CYP) enzymes in acute hepatosteatosis.
Methods: Rats were fasted for 48 h, and then provided with a high-carbohydrate/fat-free diet (FH) or a normal diet (FN) for 48 h.
Results: Hepatic lipid accumulation was significant in the FH group. In the FN group there was a small increase in microsomal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase, and erythromycin N-demethylase activities, but aminopyrine N-demethylase activity was decreased markedly. However, the microsomal enzyme activities were all inhibited by FH intake. Immunoblotting analysis showed that CYP2E1, CYP1A, CYP3A, and CYP2B1/2 proteins were decreased in the FH group. Expression of corresponding CYP mRNAs was also down-regulated. A dose of CCl4, a CYP2E1 substrate,was administered to the rats fed the different diets. The liver injury was significantly lower in the FH group as determined by elevation of serum enzyme activities and histopathological examination.
Conclusions: The results show that acute hepatosteatosis may result in a significant alteration in hepatic CYP-mediated metabolizing capacity, which can precipitate erratic responses of liver to various endogenous and exogenous substances.
Key words: hepatosteatosis, cytochrome P450, non-alcoholic fatty liver disease, drug metabolizing capacity
Downloads
Published
Issue
Section
License
Authors retain the copyright of their articles and grant the Functional Food Center (FFC) and its journals the right of first publication under the terms of the Creative Commons Attribution 4.0 International License.
This license permits unrestricted use, distribution, and reproduction in any medium, including commercial use, provided the original author(s) and source are properly credited. Authors may post and share their published work freely, provided that the original publication in this journal is acknowledged.
By submitting to this journal, authors confirm that their manuscripts are original, not under consideration elsewhere, and that they hold the necessary rights to grant this license. The Functional Food Center encourages open scientific exchange and allows derivative and extended works, provided attribution to the original publication is maintained.