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.
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Received: 29 September 1999 / Accepted: 18 October 1999
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Hanioka, N., **no, H., Chung, YS. et al. Effect of 4-tert-octylphenol on cytochrome P450 enzymes in rat liver. Arch Toxicol 73, 625–631 (2000). https://doi.org/10.1007/s002040050017
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DOI: https://doi.org/10.1007/s002040050017