title: Characterization of N-diethylnitrosamine-initiated and ferric nitrilotriacetate-promoted renal cell carcinoma experimental model and effect of a tamarind seed extract against acute nephrotoxicity and carcinogenesis.
abstract: Renal cell carcinoma (RCC), the commonest malignancy in adult kidney, lacks of early signs, resulting often in metastasis at first diagnosis. N-Diethylnitrosamine (DEN)-initiated and ferric nitrilotriacetate (FeNTA)-promoted RCC may be a useful experimental model, but it is not well characterized. In this study, histological alterations and oxidative stress markers were analyzed at different times throughout RCC development, histological subtype was re-evaluated in the light of current classification, and a tamarind seed extract (TSE) effect was examined. Male Wistar rats experimental groups were control, TSE, DEN, DEN+FeNTA, and TSE+DEN+FeNTA. TSE was given 2 weeks before DEN administration (200 mg/kg) and throughout the experiment. Fourteen days after DEN treatment, two FeNTA doses (9 mg Fe/kg) for acute nephrotoxicity study, and increasing FeNTA doses (3-9 mg Fe/kg) twice a week for 16 weeks for carcinogenesis protocol, were administered. In acute study, necrosis and renal failure were observed and TSE ameliorated them. Throughout carcinogenesis protocol, preneoplastic lesions were observed since 1 month of FeNTA treatment, which were more evident at 2 months, when also renal cysts and RCC were already detected. RCC tumors were obtained without changes in renal function, and clear cell histological subtype was identified in all cases. 4-Hydroxy-2-nonenal and 3-nitro-L: -tyrosine levels increased progressively throughout protocol. TSE decreased both oxidative stress markers and, although there was no statistical difference, it delayed RCC progress and decreased its incidence (21 %). This study brings an insight of the time course events in this carcinogenesis model, identifies clear cell subtype and establishes TSE renoprotective effects.
authors: Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Mexico, DF, Mexico. iqluna@yahoo.com
authors: Chabetty Y
authors: CY
authors: Vargas-Olvera
authors: Dolores Javier
authors: DJ
authors: Sánchez-González
authors: José D
authors: JD
authors: Solano
authors: Francisco A
authors: FA
authors: Aguilar-Alonso
authors: Fernando
authors: F
authors: Montalvo-Muñoz
authors: Claudia María
authors: CM
authors: Martínez-Martínez
authors: Omar N
authors: ON
authors: Medina-Campos
authors: María Elena
authors: ME
authors: Ibarra-Rubio
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000188:drug therapy; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004052:Diethylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000633:toxicity; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D018384:Oxidative Stress; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry; D029861:Tamarindus / Q000737:chemistry*
chemical_list: D002273:Carcinogens; D005290:Ferric Compounds; D010936:Plant Extracts; D004052:Diethylnitrosamine; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate