Protective effect of quercetin on the evolution of cisplatin-induced acute tubular necrosis.
BACKGROUND
The mechanism of cisplatin-induced nephrotoxicity is unknown, but has been associated with renal lipid peroxidation. The bioflavonoid quercetin may be a potential alternative to reduce cisplatin-induced nephrotoxicity. The aim of this study was to evaluate the effect of quercetin on the evolution of cisplatin-induced acute tubular necrosis.


METHODS
One hundred and three male Wistar rats were injected with cisplatin (5 mg/kg, i.p.), 43 of them received quercetin (50 mg/kg, by gavage) before cisplatin injection. Blood and urine were collected 5 and 20 days after the injection for the determination of plasma creatinine, urine volume and osmolality. The kidneys were removed for the determination of renal malondialdehyde (MDA) and for histological and immunohistochemical studies. The renal expression of fibronectin, alpha-smooth muscle actin, vimentin, Jun N-terminal kinase, nuclear factor-kappaB, and macrophages during the evolution of the acute tubular necrosis induced by cisplatin and the histological changes observed in the kidneys were analyzed.


RESULTS
Cisplatin-treated rats presented a transitory increase in plasma creatinine levels, tubular cell necrosis and increased immunostaining for vimentin, alpha-SM-actin, fibronectin, ED1, NF-kappaB, and p-JNK in the renal cortex and outer medulla. These alterations were less intense in animals treated with quercetin.


CONCLUSIONS
Quercetin treatment attenuated the functional, histological and immunohistochemical alterations induced by cisplatin.
Francescato
Heloísa D Coletta
HD
Department of Clinical, Toxicological and Bromatological Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
Coimbra
Terezila M
TM
Costa
Roberto S
RS
Bianchi
Maria de L P
Mde L
D000199:Actins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D003401:Creatine / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D000970:Antineoplastic Agents; D005609:Free Radicals; D016328:NF-kappa B; D014746:Vimentin; D011794:Quercetin; D009195:Peroxidase; D048031:JNK Mitogen-Activated Protein Kinases; D003401:Creatine; D002945:Cisplatin