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牛磺酸对顺铂诱导的大鼠性腺毒性和睾丸细胞凋亡作用的防御机制

The defensive role of taurine against gonadotoxicity and testicular apoptosis effects induced by cisplatin in rats.

作者信息

Azab Sherif Salah, Kamel Ihab, Ismail Nashaat Nabil, El Din Hosni Hossam, El Fatah Mohamed Abd

机构信息

Urology Department, Faculty of Medicine, October 6 University, Cairo, Egypt.

Andrology Department, Faculty of Medicine, Cairo University, Egypt.

出版信息

J Infect Chemother. 2020 Jan;26(1):51-57. doi: 10.1016/j.jiac.2019.07.004. Epub 2019 Jul 25.

Abstract

INTRODUCTION

Cisplatin (CIS), which is used as a therapeutic antineoplastic agent may produce gonadotoxicity in a process linked to chemotherapy. Taurine, through its potential antioxidant effect, has a protective role against cisplatin-induced oxidative stress and apoptosis.

OBJECTIVE

To investigate whether taurine intake can ameliorate testicular damage induced by cisplatin and to study the possible mechanism that mediates this action, either through its antioxidant action alone or in addition to its anti-apoptotic effects.

PATIENTS AND METHODS

Fifty healthy adult white male albino rats were randomly distributed into five groups, each involving ten animals. The first group represents the negative control group. The other four groups received three equal doses (3 mg/kg body weight) intraperitoneal injections of cisplatin on alternate days. In the positive control group (group 2), saline only was given. Groups 3, 4 &5 received taurine in distilled water at oral doses of 50, 150, 250 mg/kg, respectively, on alternate days followed by cisplatin (each injection of cisplatin was given 1 day after taurine). On the 28th day after the first dose of normal saline, cisplatin or taurine, blood samples were examined for testosterone levels. All rats were killed and their testes were examined.

RESULTS

Rats treated with cisplatin alone showed reduced body weight in addition to reduced testicular weight, impaired sperm counts, and oxidative stress (reduced GSH, increased MDA level), decreased plasma testosterone, apoptotic marker (increased Bax, decreased bcl2). However following taurine induction, the figures for GSH and MDA changed significantly (P < 0.005) referring to the effect of taurine as a potent antioxidant.

CONCLUSIONS

Cisplatin-induced germ cell apoptosis may result in decreasing spermatogenesis. However, taurine could effectively prevent nearly all of these cisplatin-induced testicular abnormalities, thereby proving to be an effective cytoprotectant.

摘要

引言

顺铂(CIS)作为一种治疗性抗肿瘤药物,在化疗过程中可能会产生性腺毒性。牛磺酸通过其潜在的抗氧化作用,对顺铂诱导的氧化应激和细胞凋亡具有保护作用。

目的

研究摄入牛磺酸是否能改善顺铂诱导的睾丸损伤,并探讨介导这一作用的可能机制,是仅通过其抗氧化作用,还是除了抗凋亡作用之外。

患者和方法

50只健康成年白色雄性白化大鼠随机分为五组,每组10只。第一组为阴性对照组。其他四组每隔一天腹腔注射三次等量剂量(3mg/kg体重)的顺铂。阳性对照组(第2组)仅给予生理盐水。第3、4和5组每隔一天分别口服给予50、150、250mg/kg蒸馏水溶解的牛磺酸,随后注射顺铂(每次顺铂注射在牛磺酸给药1天后进行)。在首次给予生理盐水、顺铂或牛磺酸后的第28天,检测血样中的睾酮水平。处死所有大鼠并检查其睾丸。

结果

单独用顺铂治疗的大鼠除睾丸重量减轻外,体重也减轻,精子计数受损,出现氧化应激(谷胱甘肽减少,丙二醛水平升高),血浆睾酮降低,凋亡标志物(促凋亡蛋白Bax增加,抗凋亡蛋白bcl2减少)。然而,在给予牛磺酸后,谷胱甘肽和丙二醛的数据发生了显著变化(P<0.005),表明牛磺酸具有强大的抗氧化作用。

结论

顺铂诱导的生殖细胞凋亡可能导致精子发生减少。然而,牛磺酸可以有效预防几乎所有这些顺铂诱导的睾丸异常,从而证明是一种有效的细胞保护剂。

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