Resveratrol attenuates cisplatin-induced nephrotoxicity in rats.
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.
Do Amaral
Cátia Lira
CL
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Do Café, s/n, 14041-903 Ribeirao Preto, Brazil. caamaral@fcfrp.usp.br
Francescato
Heloísa Della Coletta
HD
Coimbra
Terezila Machado
TM
Costa
Roberto Silva
RS
Darin
Joana D'arc Castania
JD
Antunes
Lusânia Maria Greggi
LM
Bianchi
Maria De Lourdes Pires
Mde L
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D053331:Ectodysplasins / Q000378:metabolism; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014554:Urination / Q000187:drug effects
D000970:Antineoplastic Agents; D000975:Antioxidants; D053331:Ectodysplasins; D013267:Stilbenes; D003404:Creatinine; D002945:Cisplatin; D000077185:Resveratrol