RESUMO
Abstract Purpose To investigate the effects of grape seed proanthocyanidin B2 (GSPB2) preconditioning on oxidative stress and apoptosis of renal tubular epithelial cells in mice after renal ischemia-reperfusion (RIR). Methods Forty male ICR mice were randomly divided into 4 groups: Group A: mice were treated with right nephrectomy. Group B: right kidney was resected and the left renal vessel was clamped for 45 minutes. Group C: mice were intraperitoneally injected with GSPB2 before RIR established. Group D: mice were intraperitoneally injected with GSPB2 plus brusatol before RIR established. Creatinine and urea nitrogen of mice were determined. Pathological and morphological changes of kidney were checked. Expressions of Nrf-2, HO-1, cleaved-caspase3 were detected by Western-blot. Results Compared to Group B, morphology and pathological damages of renal tissue were less serious in Group C. Western-blot showed that expressions of Nrf-2 and HO-1 in Group C were obviously higher than those in Group B. The expression of cleaved-caspase3 in Group C was significantly lower than that in Group B. Conclusion GSPB2 preconditioning could attenuate renal oxidative stress injury and renal tubular epithelial cell apoptosis by up-regulating expressions of Nrf-2 and HO-1 and down-regulating the expression of cleaved-caspase-3, but the protective effect could be reversed by brusatol.
Assuntos
Animais , Masculino , Camundongos , Traumatismo por Reperfusão , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proantocianidinas/uso terapêutico , Proantocianidinas/farmacologia , Extrato de Sementes de Uva/uso terapêutico , Extrato de Sementes de Uva/farmacologia , Células Epiteliais , Camundongos Endogâmicos ICRRESUMO
ABSTRACT PURPOSE: To investigate the potential effects of pretreatment with allopurinol on renal ischemia/reperfusion injury (IRI) in a rat model. METHODS: Twenty four rats were subjected to right kidney uninephrectomy were randomly distributed into the following three groups (n=8): Group A (sham-operated group); Group B (ischemic group) with 30 min of renal ischemia after surgery; and Group C (allopurinol + ischemia group) pretreated with allopurinol at 50 mg/kg for 14 days. At 72 h after renal reperfusion, the kidney was harvested to assess inflammation and apoptosis. RESULTS: Pretreatment with allopurinol significantly improved renal functional and histological grade scores following I/R injury (p<0.05). Compared with Group B, the expression levels of caspase-3 and Bax were markedly reduced in Group C, meanwhile, whereas expression of bcl-2 was clearly increased (p<0.05). A newly described marker of inflammation, High Mobility Group Box 1(HMGB1), showed reduced expression in Group C (p<0.05). CONCLUSION: Pretreatment with allopurinol had a protective effect on kidney ischemia/reperfusion injury, which might be related to the inhibition of HMGB1 expression.
Assuntos
Animais , Masculino , Traumatismo por Reperfusão/prevenção & controle , Alopurinol/farmacologia , Precondicionamento Isquêmico/métodos , Substâncias Protetoras/farmacologia , Proteína HMGB1/efeitos dos fármacos , Rim/irrigação sanguínea , Superóxido Dismutase/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Traumatismo por Reperfusão/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Apoptose/efeitos dos fármacos , Peroxidase/metabolismo , Proteína HMGB1/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Rim/patologiaRESUMO
PURPOSE:To investigate the effect of metformin on renal tubular epithelial cell apoptosis and inflammation after kidney ischemia/ reperfusion in rats.METHODS:Eighteen SD rats were randomly divided into three groups: Sham (S), Ischemia/reperfusion (I/R), and Metformin (E). Before establishing the I/R model, group E was administered metformin for three days, while groups S and I/R were administered equal volumes of saline. After three days, a right nephrectomy was performed on all groups, after which the left kidneys of groups E and I/R rats were subjected to 45 min renal ischemia. Renal function, histology, and cell apoptosis were assessed. AMPK, pAMPK, COX-2, and Caspase 3 were also detected.RESULTS:Compared to I/R group, Caspase 3 and COX-2 levels were decreased in group E. COX-2, Caspase3 and pAMPK levels were higher in groups E and I/R than in group S. The pAMPK level of group E was higher than that of I/R group, while COX-2 and caspase 3 were lower in group E than they were in the other groups. There was no significant difference between E and I/R groups in AMPK levels.CONCLUSION:Metformin preconditioning attenuated the inflammation caused by ischemia/reperfusion and inhibited the apoptosis of renal tubular epithelial cells.