氟他胺对大鼠肝生物转化酶和抗氧化功能的影响

Influence of Flutamide on Liver Biotransformation Enzymes and Antioxidation in Rats

目的 初步确定氟他胺 (flutamide,Flu)肝毒性发生的机制。方法 研究Flu 5 0、10 0、2 0 0mg/kg 3个剂量对SD大鼠的肝生物转化酶和抗氧化功能的影响。研究指标为谷丙转氨酶 (ALT)、谷草转氨酶 (AST)、碱性磷酸酶 (AKP)、总胆红素 (TBIN)、谷胱甘肽 (GSH)、谷胱甘肽 S转移酶 (GSH -ST)、谷胱甘肽过氧化物酶 (GSH Px)和肝脏指数。肝组织切片经HE染色观察其病理学改变。结果 Flu 10 0和 2 0 0mg/kg组可使血清中ALT、AST、TBIN、AKP和GSH Px水平显著升高 ,GSH含量显著降低 ,对GSH ST无明显影响。 3个剂量组 14d末的肝脏指数均明显增加。病理学观察发现Flu中、高剂量有明显肝细胞变性和坏死发生。结论 Flu对SD大鼠肝脏有一定毒性 。

Purpose: To study the liver toxicity mechanism of flutamide in SD rats. Methods: Flutamide 50,100,200 mg/kg were given to investigate the influence on liver biotransformation enzymes and antioxidation in rats. The level of ALT, AST, AKP, TBIN, GSH, GSH-ST, GSH-Px and liver index were determinated by colorimetric method. The histopathology was observed by HE staining. Results: The level of ALT, AST, TBIN, AKP and GSH-Px increased obviously in flutamide 100 and 200 mg/kg group, GSH decreased conversely. The liver index was also increased obviously in three groups of flutamide. Hepatocytes swelling and necrosis appeared in flutamide 100 and 200 mg/kg. Conclusions: The results indicated that flutamide has toxicity effect on SD rat liver, which is related to antioxidation.