Oncotarget

Research Papers:

Apocynin attenuates left ventricular remodeling in diabetic rabbits

Jiuchun Qiu, Jianping Zhao, Jian Li, Xue Liang, Yajuan Yang, Zhiwei Zhang, Xiaowei Zhang, Huaying Fu, Panagiotis Korantzopoulos, Gary Tse, Tong Liu and Guangping Li _

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Oncotarget. 2017; 8:38482-38490. https://doi.org/10.18632/oncotarget.16599

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Abstract

Jiuchun Qiu1, Jianping Zhao1, Jian Li1, Xue Liang1, Yajuan Yang1, Zhiwei Zhang1, Xiaowei Zhang1, Huaying Fu1, Panagiotis Korantzopoulos2, Gary Tse3,4, Tong Liu1, Guangping Li1

1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China

2First Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece

3Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, SAR, P.R. China

4Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, SAR, P.R. China

Correspondence to:

Tong Liu, email: liutongdoc@126.com

Guangping Li, email: tjcardiol@126.com

Keywords: left ventricular remodeling, diabetes mellitus, oxidative stress, apocynin, NADPH oxidase

Received: December 23, 2016     Accepted: March 14, 2017     Published: March 27, 2017

ABSTRACT

Introduction: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are responsible for the generation of reactive oxygen species, producing vascular and myocardial dysfunction in diabetes mellitus. However, the potential benefits of the NADPH oxidase inhibitor, apocynin, on left ventricular (LV) remodeling remain unknown.

Results: In the diabetic group, interventricular septal thickness and left ventricular posterior wall thickness were markedly increased compared to control. These changes were accompanied by increased LV cardiomyocyte cross-sectional area and greater degree of interstitial fibrosis. NO, myeloperoxidase, and malonaldehyde levels in the serum were significantly increased Moreover, protein expression levels of rac1, nuclear factor-κB, transforming growth factor-β, p38, P-p38, and metalloproteinase-9 were also raised. Apocynin treatment prevented all of these structural, histological and biochemical changes and additionally increased superoxide dismutase levels.

Methods: Thirty Japanese rabbits were randomized into three groups: control, alloxan-induced diabetes with and without apocynin treatment at 15 mg/kg/day for 8 weeks (n = 10 for each group). Echocardiography was performed and hemodynamics were assessed by carotid and LV catheterization. LV cardiomyocyte cross-sectional area and interstitial fibrosis were evaluated by histology. Serum nitric oxide (NO), malonaldehyde, myeloperoxidase, superoxide dismutase (SOD) levels, and activity of LV tissue NADPH oxidases was assessed. Expression of proteins involved in pro-inflammatory and pro-fibrotic signaling were determined by Western blotting.

Conclusions: Inhibition of NADPH oxidase using apocynin is an effective upstream therapy for preventing diabetes-induced adverse remodeling of the left ventricular myocardium.


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