title: NADPH oxidase inhibitor apocynin prevents atrial remodeling in alloxan-induced diabetic rabbits.
abstract: OBJECTIVE
  Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). The role of the NADPH oxidase (NOX) signaling in the setting of DM and the potential benefits of apocynin on diabetic atrial remodeling remain unknown.
  
  
  METHODS
  Sixty Japanese rabbits were randomized into 3 groups as follows: Control group (Control, n=20), alloxan-induced diabetic group (DM, n=20) and apocynin-treated diabetic group (APO, n=20). Rabbits in the APO group were orally administered apocynin (15mg/kg/day) for 8weeks. Serum malonaldehyde (MDA), superoxide dismutase (SOD) levels, and left atrial tissue NADPH oxidase (NOX) activities were measured. Isolated rabbit hearts were Langendorff perfused. Atrial refractory effective period (AERP), atrial effective refractory period dispersion (AERPD), interatrial conduction time (IACT) and vulnerability to AF were assessed. Atrial interstitial fibrosis was evaluated by Masson's trichrome staining. The protein expression of NF-κB, TGF-β, p38, P-p38, JNK, P-JNK, ERK and P-ERK was measured by Western blot analysis.
  
  
  RESULTS
  There were no significant differences regarding SBP, DBP, LVEDP and AERP in the three groups. Compared with the Control group, AF inducibility was increased in the DM group (46/450 vs. 5/450, P<0.05), and markedly reduced by apocynin (46/450 vs. 12/450, P<0.05). Apocynin also attenuated atrial structural remodeling in diabetic rabbits. Western-blot analysis indicated that apocynin reduced the DM-induced increased protein expression of TGF-β, NF-κB, P-p38, P-JNK, ERK and P-ERK.
  
  
  CONCLUSIONS
  Apocynin, a NADPH oxidase inhibitor, prevents AF and attenuates atrial remodeling in alloxan-induced diabetic rabbits.
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 300211, 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 300211, 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 300211, 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 300211, 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 300211, 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 300211, 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 300211, 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 300211, 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: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China. Electronic address: liutongdoc@126.com.
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 300211, People's Republic of China. Electronic address: tjcardiol@126.com.
authors.forename: Guangping
authors.initials: G
authors.lastname: Li
mesh_terms: D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000496:Alloxan; D000818:Animals; D001281:Atrial Fibrillation / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control*; D064752:Atrial Remodeling / Q000187:drug effects* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005260:Female; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation
chemical_list: D000098:Acetophenones; D000496:Alloxan; C056165:acetovanillone; D019255:NADPH Oxidases
keywords: Apocynin; Atrial remodeling; Diabetes; NADPH oxidase; Oxidative stress