RESUMO
AIM: The present study aims to investigate the protective effects of artemisinin (ATZ) on early renal damage in experimental diabetic rats and its probable mechanism. METHODS: Models of diabetic nephropathy (DN) rats was established utilizing streptozotocin (STZ)-injection intraperitoneally (55 mg/kg) method. All rats were subsequently divided into normal control group, model group and ATZ (25, 50, 75 mg/kg) group randomly. Biochemical parameters including body weight, kidney index, blood glucose, 24 h UAER, Scr, BUN, T-SOD, GSH-Px and MDA were comprehensively determined after 8-week consecutive administrations. HE and PAS stainings were performed to observe the histopathological alterations of kidney. Western blot was conducted to detect the expressions of TGF-ß1, Nrf2, HQ-1 and NQO1. KEY FINDINGS: ATZ at three concentrations in ATZ group significantly increased the body weight. Biochemical parameters altered significantly between model group and ATZ group. Moreover, ATZ inhibited TGF-ß1 protein expression and activated the Nrf2 signaling pathway. Pathological histology results revealed the alterations including mesangial cells proliferation, thickness of glomerular capillary basement membrane, extracellular matrix (ECM) and the 24 h UAER. Western blot analysis demonstrated the increase of antioxidant proteins HO-1 and NQO1 and Nrf2-related proteins. SIGNIFICANCE: ATZ could reduce early renal oxidative stress damage in DN rats by inhibiting TGF-ß1 protein expression in kidney tissues as well as activating the Nrf2 signaling pathway and enhancing the expression of antioxidant proteins, thereby exerting the protective effects on DN kidney. The current study is the first report of ATZ on attenuating effects on kidney of DN rats, which could lay solid theoretical foundations on clinical application of ATZ to treat DN.
Assuntos
Artemisininas/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Rim/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Animais , Artemisininas/farmacologia , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Peso Corporal/efeitos dos fármacos , Creatinina/sangue , Nefropatias Diabéticas/sangue , Heme Oxigenase-1/metabolismo , Rim/efeitos dos fármacos , Masculino , NAD(P)H Desidrogenase (Quinona)/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
A novel aerobic gram-negative bacterial strain capable of utilizing 2-hydroxyquinoxaline (2-HQ) as sole source of carbon and energy was isolated from Indian agricultural soil and named as HQ1. Strain HQ1 was identified as Ochrobactrum sp. on the basis of morphology, physico-biochemical characteristics and 16S rRNA sequence analysis. The generation time of Ochrobactrum sp. HQ1 on 2-HQ at log phase is 0.71 h or 42.6 min. The degradation of 2-HQ by HQ1 under various physico-chemical parameters was analysed by HPLC and observed to be optimum with a high inoculum density (1.0 OD) at pH 7-8, temperatures 37-40°C and a high concentration of 2-HQ (500 ppm). Degradation of 2-HQ was also improved when additional nitrogen sources were used and this was attributed to the enhanced growth of the bacterium on the readily available nitrogen sources. Analysis of 2-HQ degradation by GC-MS resulted in elucidation of the degradation pathway for HQ1, a novel observation for aerobic Gram-negative bacteria. These findings are a possible indication of the application of HQ1 in the bioremediation of pesticide/metabolite contamination.