Inhibition of CYP450 1A and 3A by berberine in crucian carp Carassius auratus gibelio

文献类型： 外文期刊

第一作者： Zhou, Chang

作者： Zhou, Chang;Li, Xin-Cang;Fang, Wen-Hong;Hu, Lin-Lin;Zhou, Shuai;Zhou, Jun-Fang;Zhou, Chang;Yang, Xian-Le

作者机构：

关键词： Berberine;Crucian carp;CYP1A and 3A;Inhibition

期刊名称：COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY （ 影响因子：3.228； 五年影响因子：3.289 ）

ISSN： 1532-0456

年卷期： 2011 年 154 卷 4 期

页码：

收录情况： SCI

摘要： Berberine has long been considered as an antibiotic candidate in aquaculture. However, studies regarding its effects on drug-metabolizing enzymes in fish are still limited. In the present study, the effects of berberine on cytochrome P4501A (CYP1A) and CYP3A in crucian carp were investigated. Injection of different concentrations of berberine (0, 5, 25, 50, and 100 mg/kg) inhibited the CYP1A mRNA expression, thereby inhibiting further the catalytic activity of CYP1A-related ethoxyresorufin-O-deethylase (EROD). Furthermore, both CYP1A expression and EROD activity were further inhibited with increasing berberine concentrations. In addition, the CYP3A expressions at both the mRNA and the protein levels were downregulated by higher berberine concentrations. The catalytic activity of CYP3A-related erythromycin N-demethylase (ERND) was also inhibited by berberine at a dose of no less than 25 mg/kg. Moreover, at the berberine concentration exceeding 25 mg/kg, the inhibition of CYP3A expression and ERND activity increased with increasing berberine concentrations. In vitro experiments were also performed. When berberine was pre-incubated with the crucian carp liver microsomes, it competitively inhibited the corresponding EROD activity with the IC50 of 11.7 mu M. However, the ERND activity was slightly inhibited by berberine with the IC50 of 206.4 mu M. These results suggest that, in crucian carp, berberine may be a potent inhibitor to CYP1A, whereas the CYP3A inhibition needs a higher concentration of berberine. (C) 2011 Elsevier Inc. All rights reserved.

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