Resveratrol attenuates cisplatin-induced nephrotoxicity in rats

被引:94
作者
Do Amaral, Catia Lira [1 ]
Francescato, Heloisa Della Coletta [2 ]
Coimbra, Terezila Machado [2 ]
Costa, Roberto Silva [3 ]
Castania Darin, Joana D'arc [1 ]
Greggi Antunes, Lusania Maria [1 ]
Pires Bianchi, Maria De Lourdes [1 ]
机构
[1] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut, BR-14041903 Ribeirao Preto, Brazil
[2] Univ Sao Paulo, Dept Fisiol, Fac Med Ribeirao Preto, BR-14041903 Ribeirao Preto, Brazil
[3] Univ Sao Paulo, Dept Patol, Fac Med Ribeirao Preto, BR-14041903 Ribeirao Preto, Brazil
关键词
cisplatin; resveratrol; nephrotoxicity; macrophage; T-lymphocyte;
D O I
10.1007/s00204-007-0262-x
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:363 / 370
页数:8
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