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槲皮素多次给药对顺铂诱导的大鼠肾毒性和肾氧化应激的比较研究

Comparative study of multiple dosage of quercetin against cisplatin-induced nephrotoxicity and oxidative stress in rat kidneys.

作者信息

Behling Estela B, Sendão Milena C, Francescato Heloísa D C, Antunes Lusânia M G, Costa Roberto S, Bianchi Maria de Lourdes P

机构信息

Departamento de Alimentos e Nutrição, Faculdade de Ciencias Farmaceuticas de Araraquara, UNESP, Rod. Araraquara/Jaú, km 01, 14801-902, Araraquara, SP, Brazil.

出版信息

Pharmacol Rep. 2006 Jul-Aug;58(4):526-32.

Abstract

Quercetin, a typical bioflavonoid ubiquitously present in fruits and vegetables, is considered to be helpful for human health. Cisplatin (cDDP) is one of the most active cytotoxic agents in the treatment of a wide range of solid tumors. The aim of this study was to investigate the possible effect of quercetin, a bioflavonoid with antioxidant potential, on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Gavage administrations of water, propylene glycol and quercetin (50 mg/kg) were made 24 and 1 h before saline or cDDP (5 mg/kg) ip injections and were repeated daily for 2, 5 or 20 subsequent days. Rats were killed 2, 5 and 20 days after ip injections, and blood and urine samples were collected to determine plasma creatinine, urine volume and osmolality. The kidneys were removed to determine the levels of thiobarbituric acid-reactive substances (TBARS) and for histological studies. Cisplatin increased lipid peroxidation, urine volume and plasma creatinine levels and decreased urine osmolality. Treatment with quercetin attenuated these alterations. These results demonstrate the role of oxidative stress and suggest a protective effect of quercetin on cisplatin-induced nephrotoxicity in adult Wistar rats.

摘要

槲皮素是一种广泛存在于水果和蔬菜中的典型生物类黄酮,被认为对人体健康有益。顺铂(cDDP)是治疗多种实体瘤最有效的细胞毒性药物之一。本研究旨在探讨具有抗氧化潜力的生物类黄酮槲皮素对顺铂诱导的大鼠肾毒性和脂质过氧化的可能影响。在腹腔注射生理盐水或顺铂(5mg/kg)前24小时和1小时,分别经口灌胃给予水、丙二醇和槲皮素(50mg/kg),并在随后的2、5或20天每天重复给药。腹腔注射后2、5和20天处死大鼠,采集血液和尿液样本以测定血浆肌酐、尿量和渗透压。取出肾脏以测定硫代巴比妥酸反应性物质(TBARS)水平并进行组织学研究。顺铂增加了脂质过氧化、尿量和血浆肌酐水平,并降低了尿渗透压。槲皮素治疗减轻了这些改变。这些结果证明了氧化应激的作用,并提示槲皮素对成年Wistar大鼠顺铂诱导的肾毒性具有保护作用。

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