抗癌药顺铂对小鼠的耳、肾和肝毒性及其机制的研究

Study of toxic effects on hearing, kidney and liver of mice induced by anticancer agent of cisplatin and their mechanisms

目的 以小鼠为实验对象建立抗癌药顺铂毒性研究的实验动物模型 ,并探讨其毒性作用产生的可能机制 ,为进一步对顺铂毒性作用的防治研究提供科学参考资料。方法 选择♂昆明种小鼠 ,经腹腔连续注射顺铂 5d ,观察不同剂量顺铂对小鼠的听力、肾脏和肝脏的毒性作用及肝和肾组织抗氧化系统各指标的变化。结果 顺铂可引起小鼠体重明显下降、全频率的听力阈值升高 ,肝和肾的脏器系数、血清尿素氮 (BUN)含量和丙氨酸氨基转换酶 (ALT)活性等指标的异常 ,并呈剂量依赖关系。此外 ,顺铂还可引起肝和肾抗氧化及氧化损伤指标的异常。结论 3 0～ 4 0mg·kg-1b w的顺铂可引起小鼠出现明显的听力、肾和肝组织的损伤。氧化损伤是抗癌药顺铂产生其毒性作用的可能机制之一 ,但对于不同的脏器和在不同的给药时期 。

AIM To establish an animal experimental model for study on prevention of cisplatin toxicity and explore the possible mechanisms of the toxicity induced by cisplatin administration. METHODS Cisplatin was administered i.p consecutively for five days to male mice weighted from 28 to 30 g. The toxic effects induced by different doses of cisplatin on hearing, liver and kidney were determined. RESULTS Dose dependent decrease of body weight, abnormality of kidney and liver coefficients, levels of BUN and activities of ALT in serum were induced by cisplatin administration. Furthermore, Levels of GSH, activities of GSH Px and SOD increased significantly in kidney. Reversely, levels of GSH, activities of GSH Px and SOD in liver decreased and levels of LPO increased significantly in animals given cisplatin compared with those in control animals. CONCLUSION Obvious damage on hearing, liver and kidney of mice could be induced after consecutively 5 days administration of cisplatin with doses range from 3 0 to 4 0 mg·kg -1 (body weight). Oxidative damage is one of the mechanisms of these toxic effects on liver and kidney induced by cisplatin. But for different organs or at different stages of cisplatin administration, the main mechanism may be different.