Elsevier

Biochemical Pharmacology

Volume 37, Issue 7, 1 April 1988, Pages 1203-1206
Biochemical Pharmacology

Co-induction of microsomal cytochrome P-452 and the peroxisomal fatty acid β-oxidation pathway in the rat by clofibrate and di-(2-ethylhexyl)phthalate: Dose-response studies

https://doi.org/10.1016/0006-2952(88)90771-XGet rights and content

Abstract

Male Wistar rats have been pretreated with either clofibrate or diethylhexylphthalate and the dose-dependency of induction of the microsomal, cytochrome P-452-driven fatty acid hydroxylase and peroxisomal fatty acid β-oxidation system investigated. Both clofibrate and DEHP specifically induced (approximately 10-fold) the 12-hydroxylation of lauric acid in a dose-dependent manner and only marginally increased the associated 11-hydroxylase activity. This dose-dependent increase in fatty acid hydroxylase activity was accompanied by a similar ten-fold increase in the specific content of the cytochrome P-452 isoenzyme responsible for this activity, as assessed by an immunochemical-based ELISA method. Similarly, both clofibrate and DEHP induced the peroxisomal fatty acid β-oxidation pathway in a dose-dependent manner. Furthermore, our results provide evidence that, after oral administration, clofibrate has a higher in vivo potency in inducing the above enzymes of fatty acid metabolism than is exhibited by DEHP.

A correlation matrix analysis of the above data indicated a close association between the induction of microsomal cytochrome P-452 (and its associated fatty acid hydroxylase activity) and peroxisomal β-oxidation enzymes, implicating a mechanistic inter-relationship between changes in fatty acid metabolising enzymes in these two hepatic subcellular organelles.

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