Magnesium orotate elicits acute cardioprotection at reperfusion in isolated and in vivo rat hearts

Citations Over Time

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.

Related Papers

• → Ischaemic Preconditioning Inhibits Opening of Mitochondrial Permeability Transition Pores in the Reperfused Rat Heart(2003)342 cited
• → The mitochondrial permeability transition pore as a target for preconditioning and postconditioning(2009)263 cited
• → Mitochondrial permeability transition pore-dependent necrosis(2022)148 cited
• → Inhibition of Bcl-2 Sensitizes Mitochondrial Permeability Transition Pore (MPTP) Opening in Ischemia-Damaged Mitochondria(2015)61 cited
• → Sanglifehrin A inhibits opening of mitochondrial permeability transition pore (MPTP) during ischemia/reperfusion in the adult but not in the immature heart(2006)