Selection of agents for prevention of cisplatin-induced hepatotoxicity
Selection of agents for prevention of cisplatin-induced hepatotoxicity
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DOI：
10.1016/j.phrs.2008.01.001
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发表时间：
2008-02-01
影响因子：
9.3
通讯作者：
Tang, Hao
中科院分区：
文献类型：
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作者：
Liao, Yingjun;Lu, Xiuqiang;Tang, Hao
本研究的目的是探索与顺铂沿着使用的药物的最佳组合，以保护肝毒性。动物实验采用L-8（2（7））正交设计，设7个因素，每个因素2个水平，共8组小鼠。本研究中测试的试剂为锌、硒、磷霉素、硫代硫酸钠（STS）、N-乙酰半胱氨酸（NAC）、蛋氨酸和牛磺酸。从顺铂给药前两天开始，通过管饲法向小鼠补充正交表中设计的各种试剂组合，每天一次，持续9天。3.5腹腔注射顺铂1 mg/kg体重，每日1次，连续5天。顺铂给药停止后，连续补充药物两天。停药后检测血清丙氨酸氨基转移酶（ALT）活性、肝脏谷胱甘肽（GSH）和丙二醛（MDA）含量。结果表明：锌、磷霉素和蛋氨酸是保护体重减轻的有效因素;磷霉素和蛋氨酸是防止肝率降低的有效因素;硒、磷霉素和STS是防止血清ALT活性升高的有效因素。蛋氨酸是防止肝脏GSH水平下降的唯一有效因素;锌、硒和磷霉素是防止肝脏MDA水平升高的有效因素。根据本研究中观察到的数据，试剂的最佳组合是硒、磷霉素、蛋氨酸和牛磺酸，以及锌、硒、STS和蛋氨酸。总之，本研究中使用的每种药物都可以在预防顺铂肝毒性方面发挥有益作用，但没有一种药物可以发挥关键作用。这些药物联合应用可增强顺铂肝毒性的预防作用。(C)2008爱思唯尔有限公司保留所有权利。
The objective of this study was to explore the optimal combination of agents used along with cisplatin for protection of hepatotoxicity. Animal experiment was carried out based on the orthogonal design L-8 (2(7)) setting seven factors with two different levels of each, and eight groups of mice were needed. The agents tested in this study were zinc, selenium, fosfomycin, sodium thiosulfate (STS), N-acetyl-cysteine (NAC), methionine and taurine. Mice were supplemented by gavage with various combinations of agents as designed in the orthogonal table once a day for nine days beginning two days before cisplatin administration. 3.5 mg/kg body weight of cisplatin was given intraperitoneally once a day for five days simultaneously. After cessation of cisplatin administration, the agents were supplemented continuously for two days. Activities of alanine aminotransferase (ALT) in serum, levels of glutathione (GSH) and malondialdehyde (MDA) in liver were analyzed after cessation of supplementation. Results showed zinc, fosfomycin and methionine were the effective factors for protection of weight loss; fosfomycin and methionine were the effective factors for prevention of decreased liver ratio; selenium, fosfomycin and STS were the effective factors for prevention of increased ALT activities in serum. On the other hand, methionine was the only effective factor for prevention of decreased GSH levels in liver; zinc, selenium and fosfomycin were the effective factors for prevention of increased MDA levels in liver. Based on the data observed in this study, the optimum combinations of agents were selenium, fosfomycin, methionine and taurine, and zinc, selenium, STS and methionine. In conclusion, each agent used in this study could play a beneficial role for prevention of cisplatin hepatotoxicity, however, none could play the crucial role. The potentiated actions for prevention of cisplatin hepatotoxicity could be achieved via combined use of these agents. (C) 2008 Elsevier Ltd. All rights reserved.