RESUMO
Doxorubicin (DOX) exerts toxic effects in several organs particularly kidney. The present study aimed to assess the protective effect of proanthocyanidins (PAs) against DOX-induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg, i.v.) significantly increased kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha levels, and kidney contents of malondialdehyde, nitric oxide, cyclooxygenase-2, and caspase-3 activity with significant reduction in final body weight, serum albumin, kidney contents of reduced glutathione (GSH), and superoxide dismutase activity as compared with control group. In contrast, pretreatment with PAs (200 mg/kg, p.o.) for 14 days before DOX and for 7 days after DOX ameliorated kidney function and oxidative stress parameters. Histopathological evidence confirmed the protective effects of PAs from the tissue damage induced by DOX. In conclusion, PAs have a multi-nephroprotective effect that might be attributed to its antioxidant, anti-inflammatory, and antiapoptoic activities.
Assuntos
Doxorrubicina/efeitos adversos , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/patologia , Testes de Função Renal , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Albumina Sérica/metabolismoRESUMO
This study aimed to evaluate the protective effects of alpha lipoic acid (ALA) against doxorubicin (DOX)-induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg i.v.) induced nephrotoxicity evidenced by significant elevations in kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha, and renal contents of malondialdehyde, nitric oxide, cyclooxygenase-2, and caspase-3. Also, it causes significant reduction in final body weight, serum albumin, renal contents of reduced glutathione and superoxide dismutase activity. Histopathological changes in the kidney tissue confirmed the nephrotoxic effect. In contrast, pretreatment with ALA (50 mg/kg, orally) for 14 days before DOX and for 7 days after DOX administration mitigated renal toxicity evidenced by greater improvement in the examined oxidative stress, inflammation, and apoptosis parameters. In conclusion, ALA had promising protective effects against DOX-induced nephrotoxicity that might be attributed to its antioxidant, anti-inflammatory, and antiapoptoic activities.
