RESUMO
Cisplatin (CP), as a chemotherapeutic drug, causes nephrotoxicity that has limited the clinical utility of CP. Gliclazide (GLZ), as an antihyperglycemic drug, at low dose has antioxidant property. In this study, we aimed to investigate the protective effect of GLZ against CP-induced acute renal injury. Sixty-four BALB/c mice were randomly divided into eight groups. The groups were included as control, GLZ (5, 10, and 25 mg/kg), CP, and GLZ (5, 10, and 25 mg/kg) + CP. Renal function markers (serum creatinine and blood urea nitrogen), oxidative stress markers (malondialdehyde and glutathione), apoptotic marker (caspase-3), and NF-κB were histopathologically evaluated. The results of our study showed that increased urea and creatinine were evidence of CP-induced nephrotoxicity. Histopathological examination revealed tubular epithelial and Bowman degeneration, edema, and cytoplasmic vacuolation in renal tissue structure. Administration of GLZ reduced oxidative stress, caspase-3, and NF-κB activity, and improved kidney function markers in CP-treated mice compared with CP alone group. Also, we observed that the histological tissue structure of the kidney was maintained. GLZ at dose of 25 mg/kg had higher protective effect as compared with other doses. Overall, our study suggests that GLZ with antioxidant, antiapoptotic, and anti-inflammatory properties may be a promising new therapeutic agent to prevent CP-induced nephrotoxicity.
Assuntos
Caspase 3/química , Cisplatino/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Gliclazida/farmacologia , Hipoglicemiantes/farmacologia , Nefropatias/prevenção & controle , NF-kappa B/antagonistas & inibidores , Animais , Antineoplásicos/toxicidade , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de SinaisRESUMO
Testicular dysfunction is a complication of diabetes mellitus (DM). Juglans regia L. (JRL) leaf extract is a source of phenolic compounds that exhibits hypoglycemic and antioxidative properties. We investigated whether JRL leaf extract could inhibit the adverse effects of DM on oxidative stress, testis histology and testosterone hormone production. We used four groups of male rats: control group (non-diabetic) given saline, diabetic group, diabetic + JRL group that received JRL leaf extract, and JRL group (nondiabetic) that received JRL leaf extract only. To evaluate the effects of JRL leaf extract on testicular functions in diabetic animals, we evaluated histopathological and histomorphometric changes; serum testosterone; and malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. Decreased of MDA along with improved antioxidant status in the testis of diabetic rats; these abnormalities were attenuated by JRL leaf extract. We detected significantly decreased antioxidant biomarkers (GSH, SOD, CAT) and testosterone levels in the diabetic rats; these levels were normalized after JRL leaf extract administration. The MDA level and improved antioxidant status in the testis of diabetic rats was detected after JRL leaf extract administration. Our findings suggest that JRL leaf extract exerts preventive effects against diabetic dysfunction in the testis, which might be due to its antioxidant, anti-inflammatory and anti-apoptotic properties.