Resveratrol attenuates cisplatin-induced nephrotoxicity in rats
Resveratrol attenuates cisplatin-induced nephrotoxicity in rats
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DOI：
10.1007/s00204-007-0262-x
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发表时间：
2008-06-01
影响因子：
6.1
通讯作者：
Pires Bianchi, Maria De Lourdes
中科院分区：
文献类型：
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作者：
Do Amaral, Catia Lira;Francescato, Heloisa Della Coletta;Pires Bianchi, Maria De Lourdes
顺铂是一种抗肿瘤药物，广泛应用于多种恶性肿瘤的治疗。然而，最常见的副作用，肾毒性，限制了这种药物在许多癌症患者中的使用。白藜芦醇是一种植物抗毒素，在实验性肾毒性模型中表现出高效的保护作用。本研究评价了白藜芦醇对顺铂所致肾损伤的影响。雄性Wistar大鼠用白藜芦醇（25 mg/kg b.w.，i.p.）在施用顺铂（5 mg/kgb.w.，i.p.）两到五天后被杀采集血液和尿液样本，并取出肾脏。与对照组相比，顺铂组大鼠显示急性肾小管细胞坏死，肾皮质和外髓质中ED 1（巨噬细胞/单核细胞）和T淋巴细胞的免疫染色增加。这些变化在用白藜芦醇预处理的动物中不那么强烈。此外，肾损伤的指标，如增加的血清肌酐水平，尿量和尿蛋白引起的顺铂的管理，也显着减少与白藜芦醇。白藜芦醇可降低组织中脂质过氧化和谷胱甘肽耗竭。结论：白藜芦醇通过减少自由基和抑制炎性细胞浸润减轻顺铂诱导的肾脏结构和功能变化。
Cisplatin is an antitumor drug widely used in the treatment of many malignant tumors. However, the most common adverse effect, nephrotoxicity, limits the use of this drug in many cancer patients. Resveratrol is a phytoalexin that presents highly efficient protection in experimental nephrotoxicity models. This study evaluated the effect of resveratrol on cisplatin-induced kidney damage. Male Wistar rats were treated with resveratrol (25 mg/kg b.w., i.p.) before the administration of cisplatin (5 mg/kg b.w., i.p.) and killed 2 or 5 days later. Blood and urine samples were collected and the kidneys were removed. Rats from the cisplatin group showed acute tubular cell necrosis and increased immunostaining for ED1 (macrophages/monocytes) and T-lymphocytes in the renal cortex and outer medulla when compared with the control group. These alterations were less intense in animals pre-treated with resveratrol. Moreover, indicators of renal injury such as increased serum creatinine levels, urinary volume and urinary protein caused by the administration of cisplatin, were also significantly reduced with resveratrol. Increased lipid peroxidation and glutathione depletion in tissue were attenuated by resveratrol. In conclusion, resveratrol attenuated the cisplatin-induced structural and functional renal changes by reducing free radicals and inhibiting inflammatory cell infiltrates.