title: Protective effects of a magnesium magnetic isotope (Mg25)-exchanging nanoparticle (25MgPMC16 ) on mitochondrial functional disorders in esmolol-induced cardiac arrest in rats.
abstract: In cardiac surgery, agents are needed to produce temporary cardiac arrest (cardioplegia). One of these agents is esmolol (ESM) which is a short-acting selective beta-1 adrenergic receptor antagonist and its overdose causes diastolic ventricular arrest. The (25) MgPMC(16) (porphyrin adducts of cyclohexil fullerene-C60) is known as a nanoparticle which has a cardioprotective effect when the heart is subjected to stressful conditions. In this study, we aimed to confirm the deleterious effects of ESM overdose on cardiac mitochondria and identify any protective effects of (25) MgPMC(16) in male Wistar rats. Esmolol 100 mg kg(-1) (LD50 = 71 mg kg(-1) ) was injected intravenously (i.v.) into tail vein to induce cardiac arrest. This dose was obtained from an ESM dose-response curve which induces at least 80% arrest in rats. (25) MgPMC(16) at three different doses (45, 90 and 224 mg kg(-1) ) was injected i.v. as pretreatment, eight hours before ESM injection. (25) MgCl(2) or (24) MgPMC(16) were used as controls. Following cardiac arrest, the heart was removed and the mitochondria extracted. Mitochondrial viability and the adenosine 5'-diphosphate sodium salt hydrate/Adenosine 5'-triphosphate disodium salt hydrate (ADP/ATP) ratio were measured as biomarkers of mitochondrial function. Results indicate that (25) MgPMC(16) caused a significant increase in mitochondrial viability and decrease in ADP/ATP ratio. No significant changes were seen with (24) MgPMC(16) or (25) MgCl(2) . It is concluded that cardiac arrest induced by ESM overdose leads to a significant decrease in mitochondrial viability and their ATP levels, whereas pretreatment by (25) MgPMC(16) can protect mitochondria by increasing ATP level through liberation of Mg into cells and the improvement of hypoxia.
authors.affiliation: Department of Pharmacology, Shiraz University of Medical Sciences, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Adeli
authors.forename: M R
authors.initials: MR
authors.lastname: Zarrindast
authors.forename: H
authors.initials: H
authors.lastname: Niknahad
authors.forename: S
authors.initials: S
authors.lastname: Sarkar
authors.forename: S A
authors.initials: SA
authors.lastname: Bidgoli
authors.forename: M
authors.initials: M
authors.lastname: Korani
authors.forename: P
authors.initials: P
authors.lastname: Ghasemzadeh
authors.forename: S M
authors.initials: SM
authors.lastname: Rezayat
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006323:Heart Arrest / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007554:Isotopes; D008274:Magnesium / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D053768:Metal Nanoparticles / Q000627:therapeutic use; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011166:Porphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D011412:Propanolamines / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D007554:Isotopes; D011166:Porphyrins; D011412:Propanolamines; D008274:Magnesium; C036604:esmolol