Induction of the cytochrome P450 I and IV families and peroxisomal proliferation in the liver of rats treated with benoxaprofen. Possible implications in its hepatotoxicity
- PMID:2069584
- DOI: 10.1016/0006-2952(91)90688-2
Induction of the cytochrome P450 I and IV families and peroxisomal proliferation in the liver of rats treated with benoxaprofen. Possible implications in its hepatotoxicity
Abstract
Administration of the non-steroidal anti-inflammatory drug benoxaprofen to rats gave rise to significant increases in the hepatic O-dealkylations of ethoxyresorufin and methoxyresorufin and in the 12-hydroxylation of lauric acid but, in contrast, the N-demethylation of dimethylnitrosamine was inhibited. Immunoblot studies employing solubilized microsomes from benoxaprofen-treated rats revealed that benoxaprofen increased the apoprotein levels of P450 IA1 and A2 and of P450 IVA1. The same treatment with benoxaprofen increased the beta-oxidation of palmitoyl CoA determined in liver homogenates, and immunoblot analysis showed an increase in the apoprotein levels of the trans-2-enoyl CoA hydratase bifunctional protein. It is concluded that benoxaprofen is a peroxisomal proliferator which selectively induces the hepatic cytochrome P450 I and IV families. The possible implications of these findings to the well-known hepatotoxicity of this drug are discussed.
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