Resveratrol attenuates cisplatin-induced nephrotoxicity in rats

• Published in: Archives of toxicology Vol. 82; no. 6; pp. 363 - 370
• Main Authors: Do Amaral, Cátia Lira, Francescato, Heloísa Della Coletta, Coimbra, Terezila Machado, Costa, Roberto Silva, Darin, Joana D’arc Castania, Antunes, Lusânia Maria Greggi, Bianchi, Maria De Lourdes Pires
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.06.2008; Springer; Springer Nature B.V
• Subjects: Animals; Antineoplastic Agents - toxicity; Antioxidants - pharmacology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cisplatin - toxicity; Creatinine - blood; Drug therapy; Drug Therapy, Combination; Ectodysplasins - metabolism; Environmental Health; Kidney diseases; Kidney Tubular Necrosis, Acute - chemically induced; Kidney Tubular Necrosis, Acute - pathology; Kidney Tubular Necrosis, Acute - prevention & control; Kidney Tubules - drug effects; Kidney Tubules - metabolism; Kidney Tubules - pathology; Lymphocytes; Macrophages - drug effects; Macrophages - metabolism; Male; Medical sciences; Monocytes - drug effects; Monocytes - metabolism; Occupational Medicine/Industrial Medicine; Organ Toxicity and Mechanisms; Pharmacology/Toxicology; Proteinuria - chemically induced; Proteinuria - urine; Rats; Rats, Wistar; Rodents; Side effects; Stilbenes - pharmacology; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Toxicity; Toxicology; Urination - drug effects; T-lymphocyte; Nephrotoxicity; Cisplatin; Resveratrol; Macrophage; Antineoplastic agent; Kidney disease; Urinary system disease; Rat; Toxicity; Rodentia; Antioxidant; Stilbene derivatives; Kidney; Alkylating agent; Vertebrata; Polyphenol; Mammalia; Urinary system; Phytoalexin; Animal; T-Lymphocyte; Phenols; Platinum II Complexes
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-007-0262-x

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.