title: An electrocardiographic, molecular and biochemical approach to explore the cardioprotective effect of vasopressin and milrinone against phosphide toxicity in rats.
abstract: The present study was conducted to identify the protective effect of vasopressin (AVP) and milrinone on cardiovascular function, mitochondrial complex activities, cellular ATP reserve, oxidative stress, and apoptosis in rats poisoned by aluminum phosphide (AlP). Rats were divided into five groups (n = 12) including control, AlP (12.5 mg/kg), AlP + AVP (2.0 Units/kg), AlP + milrinone (0.25 mg/kg) and AlP + AVP + milrinone. After treatment, the animals were connected to an electronic cardiovascular monitoring device to monitor electrocardiographic (ECG) parameter. Finally, oxidative stress biomarkers, mitochondrial complex activities, ADP/ATP ratio and apoptosis were evaluated on the heart tissues. Results indicated that AlP administration induced ECG abnormalities along with a decline in blood pressure and heart rate. AVP and milrinone significantly ameliorated these changes in all treated groups. Considerable protective effects on oxidative stress biomarkers, complex IV activity, ADP/ATP ratio and caspase-3 and -9 activities in treated groups were also found. These findings were supported by flow cytometry assay of cardiomyocytes. In conclusion, administration of AVP and milrinone, not only improve cardiovascular functions in AlP poisoned rats in the short time, but after a long time can also restore mitochondrial function and ATP level and reduce the oxidative damage, which prevent cardiomyocytes from entering the apoptotic phase.
authors: Department of Toxicology and Pharmacology, Faculty of Pharmacy; and Pharmaceutical Sciences Research Center; and Poisoning & Toxicology Research Center; and Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
authors: Abbas
authors: A
authors: Jafari
authors: Department of Toxicology and Pharmacology, Faculty of Pharmacy; and Pharmaceutical Sciences Research Center; and Poisoning & Toxicology Research Center; and Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Amir
authors: A
authors: Baghaei
authors: Department of Toxicology and Pharmacology, Faculty of Pharmacy; and Pharmaceutical Sciences Research Center; and Poisoning & Toxicology Research Center; and Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Reza
authors: R
authors: Solgi
authors: Department of Toxicology and Pharmacology, Faculty of Pharmacy; and Pharmaceutical Sciences Research Center; and Poisoning & Toxicology Research Center; and Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Maryam
authors: M
authors: Baeeri
authors: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mohsen
authors: M
authors: Chamanara
authors: Department of Toxicology and Pharmacology, Faculty of Pharmacy; and Pharmaceutical Sciences Research Center; and Poisoning & Toxicology Research Center; and Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Shokoufeh
authors: S
authors: Hassani
authors: Department of Toxicology and Pharmacology, Faculty of Pharmacy; and Pharmaceutical Sciences Research Center; and Poisoning & Toxicology Research Center; and Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Mahdi
authors: M
authors: Gholami
authors: Department of Toxicology and Pharmacology, Faculty of Pharmacy; and Pharmaceutical Sciences Research Center; and Poisoning & Toxicology Research Center; and Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Seyed Nasser
authors: SN
authors: Ostad
authors: Department of Toxicology and Pharmacology, Faculty of Pharmacy; and Pharmaceutical Sciences Research Center; and Poisoning & Toxicology Research Center; and Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Moahmmad
authors: M
authors: Sharifzadeh
authors: Department of Toxicology and Pharmacology, Faculty of Pharmacy; and Pharmaceutical Sciences Research Center; and Poisoning & Toxicology Research Center; and Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran. Electronic address: mohammad@tums.ac.ir.
authors: Mohammad
authors: M
authors: Abdollahi
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D017607:Aluminum Compounds / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002316:Cardiotonic Agents / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004562:Electrocardiography; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007928:Lethal Dose 50; D020105:Milrinone / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects; D009336:Necrosis; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000187:drug effects; D010720:Phosphines / Q000633:toxicity*; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014667:Vasopressins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D017607:Aluminum Compounds; D015415:Biomarkers; D002316:Cardiotonic Agents; D010720:Phosphines; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C001864:aluminum phosphide; D053148:Caspase 3; D053453:Caspase 9; D020105:Milrinone
keywords: Cardiovascular function; Milrinone; Mitochondrial toxicity; Oxidative stress; Phosphine; Vasopressin (AVP)