title: Inhibition of poly (ADP-ribose) polymerase and inducible nitric oxide synthase protects against ischemic myocardial damage by reduction of apoptosis.
abstract: Myocardial infarction (MI) is defined as the deprivation of the myocardial tissue of oxygen and nutrients, resulting in the induction of inflammation and apoptosis of the cardiomyocytes. Poly (ADP‑ribose) polymerase 1 (PARP1) is a nuclear enzyme closely associated with MI, that can be activated by DNA damage. Inducible nitric oxide synthase (iNOS) is a critical enzyme among the inflammatory cytokines. The present study aimed to investigate the underlying mechanism of the protective effects of PARP1 and iNOS inhibitor against MI, in rats. A total of 40 male Wistar rats were divided into four groups. The rats were anesthetized with sodium pentobarbital (50 mg/kg), and the left anterior descending coronary artery was occluded by ligation, using a 6‑0 polypropylene monofilament suture, at the left atrial apex, in order to induce MI. The rats from each group received an abdominal injection of either dimethylsulfoxide (100 µl, for MI group); PARP‑1 inhibitor, 3,4‑dihydro‑5‑[4‑(1‑piperidinyl)butoxy]‑1(2H)‑ isoquinolinone (DPQ; 10 mg/kg); or iNOS inhibitor, N‑(1‑naphthyl)ethylenediamine dihydrochloride (1400W; 10 mg/kg). The hearts were harvested from the rats after four weeks. Inhibition of PARP and iNOS activity improved heart function, as determined by serial echocardiography. The rate of apoptosis, as determined by a terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay, was reduced by 39.71 and 39.00% in the DPQ and 1400W groups, respectively, and this was accompanied by the downregulated expression of cleaved caspase‑3 and PARP1. Effective inhibition of PARP and iNOS, by DPQ and 1400W, was detected by western blotting and immunofluorescence, and was shown to repress O2‑ and nitrotyrosine levels, following MI. The present study confirmed that inhibition of PARP1 and iNOS was able to protect against ischemic myocardial damage, by reducing the levels of apoptosis.
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Anesthesiology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250062, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Unit, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sheng
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Anesthesiology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250062, P.R. China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001596:Benzylamines / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D000578:Amidines; D001596:Benzylamines; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D007546:Isoquinolines; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D010880:Piperidines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C108729:3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone; D052247:Nitric Oxide Synthase Type II; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3