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• W1984967504 abstract "Triptolide, a major active component of Tripterygium wilfordii Hook F (TWHF), has multiple pharmacological activities. However, its clinical use is often limited by its severe toxicity. In the present study, we evaluated the oral toxicity of triptolide in Sprague-Dawley rats for 28 days at the dosages of 0, 200 and 400microg/kg/day, respectively. Significant difference in the toxicity of triptolide at 400microg/kg was found between different sexes. The triptolide-treated female rats showed many abnormalities, including anorexia, diarrhea, leanness, suppression of weight gain and food intake, fatty liver, splenomegaly and atrophy of ovaries. In contrast, no such abnormalities were observed in male rats except for the significant reproductive toxicity. Furthermore, the metabolism of triptolide in liver microsomes from both sexes was investigated by HPLC. A greater rate of triptolide metabolism was observed in male rat hepatic microsomes, suggesting that one of the cytochrome P450s (CYPs) responsible for triptolide metabolism is male-specific or predominant at least. The inhibition experiments with CYP inhibitors showed that CYP3A and CYP2B were mainly involved in the metabolism of triptolide. In addition, since CYP3A2 is a male-predominant form in rats, significant sex difference in the metabolism of triptolide disappeared in vitro after anti-rat CYP3A2 antibody pretreatment. Results suggested that CYP3A2 made an important contribution to the sex-related metabolism of triptolide, which may result in the sex differences in triptolide toxicity." @default.
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• W1984967504 date "2010-04-01" @default.
• W1984967504 modified "2023-10-06" @default.
• W1984967504 title "Sex differences in subacute toxicity and hepatic microsomal metabolism of triptolide in rats" @default.
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• W1984967504 doi "https://doi.org/10.1016/j.tox.2010.03.004" @default.
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