1. Effect of 4- tert -octylphenol on cytochrome P450 enzymes in rat liver
- Author
-
Nobumitsu Hanioka, Toshiko Tanaka-Kagawa, Hideto Jinno, Tetsuji Nishimura, Youn-Son Chung, and Masanori Ando
- Subjects
Male ,medicine.medical_specialty ,Cytochrome ,Health, Toxicology and Mutagenesis ,Toxicology ,Rats, Sprague-Dawley ,Surface-Active Agents ,Cytochrome P-450 Enzyme System ,Phenols ,Cytochrome P-450 CYP1A2 ,Internal medicine ,medicine ,Animals ,Cytochrome P-450 CYP3A ,Cytochrome P450 Family 2 ,Testosterone ,Unspecific monooxygenase ,biology ,Chemistry ,Body Weight ,CYP1A2 ,Membrane Proteins ,Cytochrome P450 ,General Medicine ,CYP2E1 ,Monooxygenase ,Rats ,Kinetics ,Endocrinology ,Liver ,Steroid 16-alpha-Hydroxylase ,Steroid Hydroxylases ,Toxicity ,biology.protein ,Cytochromes ,Aryl Hydrocarbon Hydroxylases - Abstract
The effects were studied of 4-tert-octylphenol (OP) on hepatic cytochrome P450 enzymes in rats. Rats were treated intraperitoneally with OP twice, at doses of 5, 10, and 20 mg/kg. Among the cytochrome P450-dependent monooxygenase activities, testosterone 2α-hydroxylase activity, which is associated with CYP2C11, was significantly decreased by OP at all doses. The level relative to control activity was 67–22%. CYP3A2-dependent monooxygenase, testosterone 6β-hydroxylase activity was also decreased by 51% by OP at 20 mg/kg. Furthermore, immunoblotting showed that OP (10 or 20 mg/kg) significantly decreased CYP2C11/6 and CYP3A2/1 protein levels. However, the reduction ratio of CYP2C11/6 and CYP3A2/1 protein levels by OP treatment was lower than that of testosterone 2α-hydroxylase and testosterone 6β-hydroxylase activities. The Cl int (V max/K m) value for testosterone 2α-hydroxylase was significantly decreased by OP at all doses, whereas the Cl int value for testosterone 6β-hydroxylase was only decreased by OP at 20 mg/kg. In addition, 7-ethoxycoumarin O-deethylase activity was significantly decreased by 32% by the highest dose of OP. By contrast, CYP1A1-, CYP1A2-, CYP2A1-, CYP2B1/2-, CYP2D1-, CYP2E1- and CYP4A1/2/3- dependent monooxygenase activities were not affected by OP at any dose. These results suggest that OP changes the male-specific cytochrome P450 isoforms in rat liver, and that these changes closely relate to the toxicity of OP.
- Published
- 2000