title: The cardioprotective effect of TG-6, a newly synthesized compound, on ischemia-reperfusion injury in rats.
abstract: We tested 3-nitro-4-((4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)methyl) benzoylguanidine tartrate (TG-6) which is combinated of two known cardioprotective agents cariporide and trimetazidine, whether additively to reduce ischemia-reperfusion injury in rats. Using models of in vitro perfusion (Langendorff system) and in vivo open chest left anterior descending coronary artery ligation causing ischemia-reperfusion injury. We also used Fura-2 to measure the cytosolic Ca²⁺ concentrations ([Ca²⁺]i) in cardiomyocytes, western blot analysis the protein expression of Kv1.4, Kv4.2, Kv4.3 in myocardial ischemia-reperfusion rats. TG-6 improved the cardiac function in both in vivo and in vitro models, lowered Lactate Dehydrogenase (LDH), Creatine Kinase (CK), Malodialdehyed (MDA) activity while enhanced Superoxide Dismutase (SOD) activity. High dose of TG-6 improved the hypoxia injury of cardiomyocytes induced by sodium dithionite (Na₂S₂O₄), enhanced the viability and decreased the [Ca²⁺]i. It also down-regulated the expression of Kv1.4 and increased the expression of Kv4.2 and Kv4.3, so it might through regulating the expression of the transient outward potassium current (Ito) to improve the cardiac function.
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Guoqing
authors.initials: G
authors.lastname: Gong
authors.forename: Wenhui
authors.initials: W
authors.lastname: Yang
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Yungen
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D020033:Protein Isoforms / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051637:Shaker Superfamily of Potassium Channels / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: C574796:3-nitro-4-((4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)methyl) benzoylguanidine; D002316:Cardiotonic Agents; D006146:Guanidines; D010879:Piperazines; D020033:Protein Isoforms; D051637:Shaker Superfamily of Potassium Channels; D013482:Superoxide Dismutase