Extracellular superoxide dismutase ameliorates streptozotocin-induced rat diabetic nephropathy via inhibiting the ROS/ERK1/2 signaling

Chia Wen Kuo, Chih Jie Shen, Yu Tang Tung, Hsiao Ling Chen, Yu Hsuan Chen, Wen Hui Chang, Kai Chung Cheng, Shang Hsun Yang, Chuan Mu Chen

研究成果: 雜誌貢獻文章同行評審

41 引文 斯高帕斯(Scopus)

摘要

Aim Diabetic nephropathy is the leading cause of end stage renal disease in developed countries throughout the world. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system is the main problem that is responsible for the progression of diabetic kidney disease. In this study, we investigated whether human extracellular superoxide dismutase (hEC-SOD) can prevent diabetic nephropathy in the rat model. Main methods Diabetic nephropathy symptoms were induced by intraperitoneal injection with 60 mg/kg streptozotocin (STZ) in male Sprague-Dawley (SD) rats. After daily supplement of rhEC-SOD (3200 U/kg/day) for 4 weeks, the serum or urine biochemical markers (glucose, creatinine, blood urea nitrogen, triglyceride, hemoglobin A1c, and microalbuminuria), histological changes, gene expressions (phox47, opn, and gapdh), and protein levels (TGF-β, AT1-R, phospho-p42/p44 MAPK, and p42/p44 MAPK) were determined. Key findings Results showed that rhEC-SOD administration could reverse SOD activity measured in kidney and diabetic-associated changes, including the fibrosis change, expression of collagen I, transforming growth factor-beta (TGF-β) and angiotensin II type I receptor (AT1-R), as well as the activation of the intracellular mitogen-activated protein kinase (MAPK) signaling pathway, associating with its inhibition of p42MAPK/p44MAPK (ERK1/2) phosphorylation. Additionally, diabetic nephropathy up-regulated the expression of the phox47 and opn genes, and these changes could also be suppressed. Though the proteinuria did not significantly reduce. Treatment with rhEC-SOD ameliorates STZ-induced diabetic nephropathy, leading to reduced death rates, kidney weight/body weight ratio, fibrosis change, and TGF-β1 expression through the down-regulation of ROS/ERK1/2 signaling pathway. Significance We conclude that rhEC-SOD can act as a therapeutic agent to protect the progression of diabetic nephropathy.
原文英語
頁(從 - 到)77-86
頁數10
期刊Life Sciences
135
DOIs
出版狀態已發佈 - 6月 22 2015
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ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)
  • 藥理學、毒理學和藥劑學 (全部)

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