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

doi:10.1016/0006-2952(88)90771-X

Biochemical Pharmacology

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

https://doi.org/10.1016/0006-2952(88)90771-X Get 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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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

Abstract

Food Cosmet. Toxic.

Biochem. Pharmac.

Toxic. appl. Pharmac.

Toxic. appl. Pharmac.

J. biol. Chem.

Toxic. appl. Pharmac.

J. biol. Chem.

Toxic. appl. Pharmac.

Food Cosmet. Toxic.

Toxic. appl. Pharmac.

Toxic. Environ. Hlth

C.R.C. Crit. Rev. Toxic.