title: Apocynin attenuates left ventricular remodeling in diabetic rabbits.
abstract: BACKGROUND
  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.
authors.affiliation: Tianjin 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.
authors.forename: Jiuchun
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Tianjin 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.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Tianjin 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Tianjin 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.
authors.forename: Xue
authors.initials: X
authors.lastname: Liang
authors.affiliation: Tianjin 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.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Tianjin 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.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Tianjin 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.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Tianjin 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.
authors.forename: Huaying
authors.initials: H
authors.lastname: Fu
authors.affiliation: First Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Korantzopoulos
authors.affiliation: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.|Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Gary
authors.initials: G
authors.lastname: Tse
authors.affiliation: Tianjin 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.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Tianjin 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.
authors.forename: Guangping
authors.initials: G
authors.lastname: Li
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; C056165:acetovanillone
keywords: NADPH oxidase; apocynin; diabetes mellitus; left ventricular remodeling; oxidative stress