title: Magnesium orotate elicits acute cardioprotection at reperfusion in isolated and in vivo rat hearts.
abstract: Orotic acid and its salts chronically administered have been shown to significantly improve cardiac function in pathological settings associated with ischemia-reperfusion (I/R) injury. The aim of our study was to investigate the effect of magnesium orotate (Mg-Or) administration at the onset of post-ischemic reperfusion on myocardial function and infarct size (IS). Ex-vivo experiments performed on isolated perfused rat hearts were used to compare Mg-Or administration with a control group (buffer treated), ischemic post-conditioning, orotic acid treatment, and MgCl2 treatment. Mg-Or administration was also investigated in an in-vivo model of regional I/R performed in rats undergoing reversible coronary ligation. The effect of Mg-Or on mitochondrial permeability transition pore (mPTP) opening after I/R was investigated in vitro to gain mechanistic insights. Both ex-vivo and in-vivo experiments showed a beneficial effect from Mg-Or administration at the onset of reperfusion on myocardial function and IS. In-vitro assays showed that Mg-Or significantly delayed mPTP opening after I/R. Our data suggest that Mg-Or administered at the very onset of reperfusion may preserve myocardial function and reduce IS. This beneficial effect may be related to a significant reduction of mPTP opening, a usual trigger of cardiac cell death following I/R.
authors: Department of Pathophysiology, University of Medicine and Pharmacy, Timisoara, Romania.
authors: Silvia N
authors: SN
authors: Mirica
authors: Oana M
authors: OM
authors: Duicu
authors: Simona L
authors: SL
authors: Trancota
authors: Ovidiu
authors: O
authors: Fira-Mladinescu
authors: Denis
authors: D
authors: Angoulvant
authors: Danina M
authors: DM
authors: Muntean
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D066298:In Vitro Techniques; D057775:Ischemic Postconditioning / Q000379:methods*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009963:Orotic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009963:Orotic Acid; C104468:magnesium orotate