Hakuei Yamashita, T. Kazawa, Y. Minatogawa, T. Ebisawa, T. Yamauchi
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引用次数: 13
摘要
最近的研究表明卡马西平(CBZ)诱导肝细胞色素p450 (CYP)蛋白亚家族。本研究检测了大鼠肝CYP亚家族(2B, 3A)出现的时间过程，以及CBZ治疗诱导的CBZ及其代谢物CBZ环氧化物(CBZE)的血清水平。雄性Wistar大鼠每1 kg饲料给予5 g CBZ (CBZ处理)，连续饲喂3、7、14、28和42 d或不饲喂CBZ(对照组)。采用高效液相色谱法测定血清CBZ、CBZE水平。Western blotting检测CYP2B和CYP3A的诱导率。CBZ和CBZE分别在给药14 d和7 d后达到最大。与最大剂量相比，42 d CBZ后两者均逐渐降低。在CBZ处理3、7、14、28和42 d时，CYP2B的诱导率无显著差异。CYP3A的诱导率在CBZ 14 d时达到最大值，在CBZ 28和42 d时显著降低。CBZ慢性治疗诱导CYP2B和CYP3A的差异是一个新的发现。
Time-course of hepatic cytochrome p450 subfamily induction by chronic carbamazepine treatment in rats.
Recent studies indicate that carbamazepine (CBZ) induces hepatic cytochrome p450 (CYP) protein subfamilies. The present study examines the time-course of the appearance of hepatic CYP subfamilies (2B, 3A) and serum levels of CBZ and its metabolite, CBZ epoxide (CBZE), induced by CBZ treatment in rats. Male Wistar rats were given 5 g of CBZ (CBZ-treated) per 1 kg of feed for 3, 7, 14, 28 and 42 d or feed without CBZ (control). Serum levels of CBZ and CBZE were evaluated by HPLC. Induction ratios of CYP2B and CYP3A were evaluated by Western blotting. Serum levels of CBZ and CBZE became maximal after 14 and 7 d, respectively, after CBZ treatment. Both levels gradually, then significantly decreased after 42 d CBZ compared with maximal levels. The induction ratio of CYP2B did not differ between 3, 7, 14, 28 and 42 d CBZ treatment. The induction ratio of CYP3A reached a maximum after 14 d CBZ, then significantly decreased after 28 and 42 d CBZ compared to the maximal rate. The difference between CYP2B and CYP3A induction by CBZ chronic treatment is a novel finding.
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