Piperazine ferulate ameliorates the development of diabetic nephropathy by regulating endothelial nitric oxide synthase

Yang,Yong‑Yu; Shi,Ling‑Xing; Li,Jian‑He; Yao,Liang‑Yuan; Xiang,Da‑Xiong

doi:10.3892/mmr.2019.9875

Piperazine ferulate ameliorates the development of diabetic nephropathy by regulating endothelial nitric oxide synthase

Authors:
- Yong‑Yu Yang
- Ling‑Xing Shi
- Jian‑He Li
- Liang‑Yuan Yao
- Da‑Xiong Xiang
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Affiliations: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Pharmacology, Changsha Medical University, Changsha, Hunan 410219, P.R. China, Hunan Provincial Engineering Research Center of Translational Medical and Innovative Drug, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
Published online on: January 17, 2019 https://doi.org/10.3892/mmr.2019.9875
Pages: 2245-2253
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic nephropathy (DN) is among the most common complications of diabetes mellitus. The disorder is associated with a decrease in the activity of the nitric oxide synthase/nitric oxide system. Piperazine ferulate (PF) is widely used for the treatment of kidney disease in China. The aim of the present study was to examine the effects of PF on streptozotocin (STZ)‑induced DN and the underlying mechanism of this process. STZ‑induced diabetic mice were intragastrically administered PF (100, 200 and 400 mg/kg/body weight/day) for 12 weeks. At the end of the treatment period, the parameters of 24‑h albuminuria and blood urea nitrogen, creatinine and oxidative stress levels were measured. Hematoxylin and eosin staining, periodic acid‑Schiff staining and electron microscopy were used to evaluate the histopathological alterations. mRNA and protein expression of endothelial nitric oxide synthase (eNOS) were measured by quantitative polymerase chain reaction and western blotting, respectively. PF significantly decreased blood urea nitrogen and creatinine levels and 24‑h albuminuria, and it alleviated oxidative stress, improved glomerular basement membrane thickness and caused an upregulation in eNOS expression and activity levels in diabetic mice. In addition, high glucose decreased eNOS expression levels, whereas PF caused a reversal in the nitric oxide (NO) levels of glomerular endothelial cells. The present results suggested that PF exhibited renoprotective effects on DN. The mechanism of its action was associated with the regulation of eNOS expression and activity.

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