Fatima Sabiha, Arivarasu N A, Mahmood Riaz
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202002 UP, India.
Hum Exp Toxicol. 2007 May;26(5):419-26. doi: 10.1177/0960327106072389.
Cisplatin is a widely used antineoplastic agent that exhibits dose limiting nephrotoxicity. We have previously shown that the administration of cisplatin results in decrease in the activities of renal brush border membrane (BBM) enzymes and transport of inorganic phosphate (Pi) across BBM vesicles. In the present study we have investigated the effect of pre-treatment with vitamin C (ascorbic acid) on cisplatin-induced nephrotoxicity and changes in BBM enzymes and Pi transport. Administration of a single dose of cisplatin (6 mg/kg body weight) caused nephrotoxicity in rats that manifested biochemically as an elevation of serum urea nitrogen and creatinine levels. Treatment of rats with a single dose of vitamin C, six hours prior to administration of cisplatin, protected the kidney from the damaging effect of cisplatin. Vitamin C pre-treatment significantly decreased the urea nitrogen and creatinine levels. It attenuated the cisplatin-induced reduction in the activities of BBM and anti-oxidant enzymes and also Pi transport. These results suggest that vitamin C is an effective chemoprotectant against cisplatin-induced acute renal failure and dysfunction of the renal BBM in rats.
顺铂是一种广泛使用的抗肿瘤药物,具有剂量限制性肾毒性。我们之前已经表明,给予顺铂会导致肾刷状缘膜(BBM)酶活性降低以及无机磷酸盐(Pi)跨BBM囊泡的转运减少。在本研究中,我们研究了维生素C(抗坏血酸)预处理对顺铂诱导的肾毒性以及BBM酶和Pi转运变化的影响。给予单剂量顺铂(6mg/kg体重)会导致大鼠肾毒性,生化表现为血清尿素氮和肌酐水平升高。在给予顺铂前6小时用单剂量维生素C治疗大鼠,可保护肾脏免受顺铂的损伤作用。维生素C预处理显著降低了尿素氮和肌酐水平。它减轻了顺铂诱导的BBM和抗氧化酶活性以及Pi转运的降低。这些结果表明,维生素C是一种有效的化学保护剂,可对抗顺铂诱导的大鼠急性肾衰竭和肾BBM功能障碍。