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目的:观察新药乙烷硒啉(BBSKE)对肿瘤H-22引起的小鼠肝脏细胞色素P450含量及其主要亚型活性变化的影响。方法:H-22荷瘤小鼠,给予不同剂量的BBSKE10d后,提取肝微粒体,Omura法测定CYP450的含量,分光光度法测定CYP1A,CYP3A和CYP2E1活性。结果:肿瘤H-22能引起CYP1A活性升高(P<0.01),CYP3A活性降低(P<0.01);BBSKE能明显下调荷瘤鼠CYP1A活性,上调CYP3A活性作用(P<0.05)。肿瘤H-22和BBSKE对CYP450含量和CYP2E1均无明显影响。结论:BBSKE对荷瘤鼠CYP1A活性有下调作用;对CYP3A有诱导作用;对CYP2E1无明显影响。
OBJECTIVE: To observe the effect of ethambutol (BBSKE) on the changes of hepatic cytochrome P450 and its major subtypes in mice induced by tumor H-22. Methods: H22 tumor-bearing mice were treated with different doses of BBSKE for 10 days. Liver microsomes were extracted and the content of CYP450 was determined by Omura method. The activities of CYP1A, CYP3A and CYP2E1 were determined by spectrophotometry. Results: Tumor H-22 could induce CYP1A activity (P <0.01) and CYP3A activity (P <0.01). BBSKE could obviously down-regulate CYP1A activity and up-regulate CYP3A activity (P <0.05). Tumor H-22 and BBSKE had no significant effect on CYP450 content and CYP2E1. CONCLUSION: BBSKE can down-regulate CYP1A activity of tumor-bearing mice, induce CYP3A, and have no effect on CYP2E1.