Oxidative stress mediated mitochondrial damage plays roles in pathogenesis of diabetic nephropathy rat

X. Chen, M. Fang

Department of Endocrinology, Yiwu Central Hospital, Yiwu, Zhejiang, China. zudc8rjmfc71@sina.com

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• Metabolism

OBJECTIVE: Diabetic nephropathy (DN) is considered as a complication of diabetes and accounts for about 40%. Reactive oxygen species (ROS) level continues to increase in DN. However, whether specific ROS levels can alleviate renal damage by improving mitochondrial function has not been investigated.

MATERIALS AND METHODS: DN model was established by intraperitoneal injection of streptozotocin (STZ). The rats were divided into normal group, STZ model group, and N-acetylcysteine (NAC) group. Fasting blood glucose was tested to assess the modeling. The renal injury was evaluated by using hematoxylin-eosin (HE) staining and periodate-Schiff staining. Serum creatinine and 24 h urinary protein levels were determined by renal function detection kit. The levels of ROS and malondialdehyde (MDA) were assessed by the kit to evaluate the effects of oxidative stress and NAC in rats. The mitochondrial damage marker Cyto C level was detected by Western blot.

RESULTS: Blood glucose, serum creatinine, and urinary protein levels were significantly increased in model group compared with the normal group (p<0.05). Blood glucose levels, serum creatinine, and urinary protein levels were markedly improved after the ROS and MDA levels reduced by NAC. Meanwhile, glomerular hypertrophy, mesangial matrix accumulation, and severe renal injury were observed in the model group. NAC administration markedly improved glomerular morphology and mesangial matrix aggregation. Cyto C expression in the model group increased significantly compared with normal control group (p<0.05), while NAC effectively inhibited Cyto C levels.

CONCLUSIONS: Oxidative stress-mediated mitochondrial damage is an important part of the pathogenesis of DN. Inhibition of ROS production can be a potential target for DN treatment.

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