硒对顺铂毒性和肿瘤生长的影响及其与金属硫蛋白的关系探讨

DETOXIFYING EFFECT OF LISHENG-SE ON CISPLATIN AND ITS RELATION TO METALLOTHIONEIN INDUCTION

观察硒利生对顺铂毒性和小鼠肿瘤生长的影响，发现硒利生对顺铂致死毒性，肾脏和造血系统毒性均有不同程度保护作用，其效果优于亚硒酸钠和现已证实可诱导金属硫蛋白（ＭＴ）合成、降低顺铂毒性的有效药物次硝酸铋。经ＭＴ测定结果表明，硒利生的ＭＴ诱导作用最强（Ｐ＜０．０１），亚硒酸钠次之。由此证明了诱导体内ＭＴ增加是应用微量元素药物解救顺铂引起的重金属中毒的环节之一，但两者均不引起肿瘤中ＭＴ升高。体内抑瘤实验和体外细胞毒实验提示，硒利生对肿瘤生长没有促进作用，也不降低顺铂疗效。

Abstract The effects of Lisheng-Se(Seleninized wheat germ)on metallothionein (MT)induction,lethalsystemic toxicity,nephrotoxicity, hemotoxicity and anticancer activity of cisplatin (CDDP),were investigated in mice. The systemic toxicity of CDDP was significantly reduced by preadministration of Lisheng-Se(P<0.05 or P< 0.01).The protective effects were better than its inorganic form(Na2SeO3)and Bi(BSN),(0.05 < P< 0.1).The MT level in the liver, kidney,heart and tumor tis-sues of mice treated with one of those compounds was determined.The results show that the levelsof MT induced by Lisheng- Se were significantly increased in liver and kidney(P<0.01 andP<0.05).It was just in conformity with the conclusion that the best protective effect appeared inthe groups treated with Lisheng- Se. These results suggest that increased MT synthesis in the liverand kidney may be involved in the protective effects of Lisheng-Se tested on the lethal toxicity,nephrotoxicity and hemotoxicity produced by CDDP. The experiments also show that Lisheng-Sedid not affect the anticancer activity of CDDP in viro and in vivo, while the MT level was not in- creased in cancer(P<0.05),so Lisheng-Se might not only improve the therapeutic index ofCDDP,but also did not cause drug-resistance of cancer cells.