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Hum Exp Toxicol ; 30(7): 603-15, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20650967

RESUMO

We investigated whether pravastatin ameliorates renal damage induced by cisplatin (CP). Forty-three male Wistar rats were divided into four groups: rats treated with a control diet for 19 days and saline injection on day 14 (group1), group 1 with pravastatin treatment with 19 days (group 2), group 1 with CP injection on day 14 (group 3), and group 2 with CP injection (group 4). Renal function and serum lipids, renal malondialdehyde (MDA) and glutathione (GSH) levels, glutathione peroxidase (GPx) mRNA expression and activity, and kidney triglyceride (TG) concentrations were measured. Histology was evaluated by light microscopy with immunohistochemistry for p53, p53-upregulated modulation of apoptosis (PUMA), and terminal deoxynucleotide transferase dUTP nick end-labeling (TUNEL) staining. CP induced renal tubular damage with a higher MDA level, increased PUMA expression, p53- and TUNEL-positive cells counts, elevation of serum lipids, and decreased GSH level, GPx mRNA expression, and activity. Pravastatin partially ameliorated CP-induced renal injury, based on suppression of the renal MDA and TG levels, decreased p53 expression, and apoptosis in CP-treated rats. These findings suggest that pravastatin has a partial protective effect against CP nephrotoxicity via antioxidant activity as well as attenuation of the p53 response, and lipid-lowering effects.


Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Pravastatina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/patologia , Testes de Função Renal , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
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