Arivarasu N A, Priyamvada Shubha, Mahmood Riaz
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, U.P., India.
Exp Toxicol Pathol. 2013 Jan;65(1-2):21-5. doi: 10.1016/j.etp.2011.05.004. Epub 2011 Jun 2.
Cisplatin (CP) is a widely used antineoplastic drug that exhibits gastrointestinal toxicity. We have previously shown that administration of a single dose of CP results in a decrease in the activities of several brush border membrane (BBM) enzymes, induces oxidative stress and alters the activities of several antioxidant enzymes in the small intestine of rats. In the present study we have investigated the effect of treatment with the dietary antioxidant caffeic acid (CA) on CP induced biochemical changes in the intestine. Administration of a single intraperitoneal dose of CP alone (6 mg/kg body weight) led to a decrease in the activities of the BBM enzymes, increase in lipid peroxidation, decrease in sulfhydryl groups and changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, glucose 6-phosphate dehydrogenase, glutathione reductase, glutathione S-transferase and thioredoxin reductase. Administration of two doses of CA (each of 250 mg/kg body weight), at 15 and 120 min after treatment with CP, significantly attenuated the CP-induced changes in all these parameters but the administration of CA alone had no effect. These results suggest that CA is an effective agent in reducing the effects of CP on the intestine and could prove to be useful in alleviating the gastrointestinal toxicity of this drug.
顺铂（CP）是一种广泛使用的具有胃肠道毒性的抗肿瘤药物。我们之前已经表明，单次给予CP会导致几种刷状缘膜（BBM）酶的活性降低，诱导氧化应激，并改变大鼠小肠中几种抗氧化酶的活性。在本研究中，我们研究了膳食抗氧化剂咖啡酸（CA）对CP诱导的肠道生化变化的影响。单独腹腔注射单次剂量的CP（6 mg/kg体重）导致BBM酶活性降低、脂质过氧化增加、巯基减少以及过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶、葡萄糖6-磷酸脱氢酶、谷胱甘肽还原酶、谷胱甘肽S-转移酶和硫氧还蛋白还原酶的活性发生变化。在CP治疗后15分钟和120分钟给予两剂CA（各250 mg/kg体重），显著减轻了CP诱导的所有这些参数的变化，但单独给予CA没有效果。这些结果表明，CA是一种有效减轻CP对肠道影响的药物，可能有助于减轻该药物的胃肠道毒性。
