TY - JOUR
T1 - 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
AU - Vargas-Olvera, Chabetty Y.
AU - Sánchez-González, Dolores Javier
AU - Solano, José D.
AU - Aguilar-Alonso, Francisco A.
AU - Montalvo-Muñoz, Fernando
AU - Martínez-Martínez, Claudia María
AU - Medina-Campos, Omar N.
AU - Ibarra-Rubio, María Elena
N1 - Funding Information:
Acknowledgments This study was supported by Universidad Nacional Autónoma de México-Dirección General de Asuntos del Personal Académico-Programa de Apoyo a Proyectos de Investiga-ción e Innovación Tecnológica (UNAM-DGAPA-PAPIIT) under projects IN214307 and IN227010; by Consejo Nacional de Ciencia y Tecnología (CONACYT) 81026 and PAIP 6190-10 given to MEIR. CYVO and FAAA received a fellowship from CONACYT. The authors appreciate the collaboration of M. V. Z. Lucía Macías Rosales for her valuable assistance in animal care and treatment. The funding sponsors had no involvement in this study design, the data collection, analysis and interpretation, the manuscript writing, or the decision to submit the manuscript for publication.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Acute nephrotoxicity
KW - Carcinogenesis
KW - Ferric nitrilotriacetate
KW - Oxidative stress
KW - Renal cell carcinoma
KW - Tamarindus indica
UR - http://www.scopus.com/inward/record.url?scp=84865660200&partnerID=8YFLogxK
U2 - 10.1007/s11010-012-1373-0
DO - 10.1007/s11010-012-1373-0
M3 - Artículo
C2 - 22761015
AN - SCOPUS:84865660200
SN - 0300-8177
VL - 369
SP - 105
EP - 117
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -