Protective effects of a magnesium magnetic isotope (Mg25)‐exchanging nanoparticle (25MgPMC16) on mitochondrial functional disorders in esmolol‐induced cardiac arrest in rats
1 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.
2 The 25MgPMC16 (porphyrin adducts of cyclohexil fullerene‐C60) is known as a nanoparticle which has a cardioprotective effect when the heart is subjected to stressful conditions.
3 In this study, we aimed to confirm the deleterious effects of ESM overdose on cardiac mitochondria and identify any protective effects of 25MgPMC16 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.
4 25MgPMC16 at three different doses (45, 90 and 224 mg kg−1) was injected i.v. as pretreatment, eight hours before ESM injection. 25MgCl2 or 24MgPMC16 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.
5 Results indicate that 25MgPMC16 caused a significant increase in mitochondrial viability and decrease in ADP/ATP ratio. No significant changes were seen with 24MgPMC16 or 25MgCl2. 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 25MgPMC16 can protect mitochondria by increasing ATP level through liberation of Mg into cells and the improvement of hypoxia.
Document Type: Research Article
Affiliations: 1: Department of Pharmacology, Faculty of Medicine 2: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences 3: Department of Nanotechnology, School of Advanced Sciences and Technology in Medicine, Tehran University of Medical Sciences (TUMS) 4: Department of Toxicology & Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran
Publication date: 01 April 2012