title: Molecular and biochemical evidences on the protective effects of triiodothyronine against phosphine-induced cardiac and mitochondrial toxicity.
abstract: OBJECTIVE
  Aluminum phosphide (AlP) is a widely used fumigant and rodenticide. While AlP ingestion leads to high mortality, its exact mechanism of action is unclear. There are ample evidences suggesting cardioprotective effects of triiodothyronine (T3). In this study, we aimed to examine the potential of T3 in the protection of a rat model of AlP induced cardiotoxicity.
  
  
  METHODS
  In order to induce AlP intoxication animals were intoxicated with AlP (12 mg/kg; LD50) by gavage. In treatment groups, T3 (1, 2 and 3 μg/kg) was administered intra-peritoneally 30 min after AlP administration. Animals were connected to the electronic cardiovascular monitoring device simultaneously after T3 administration. Then, electrocardiogram (ECG), blood pressure (BP), and heart rate (HR) were monitored for 180 min. Additionally, 24h after AlP intoxication, rats were deceased and the hearts were dissected out for evaluation of oxidative stress, cardiac mitochondrial function (complexes I, II and IV), ATP/ADP ratio, caspases 3 & 9, and apoptosis by flow cytometry.
  
  
  RESULTS
  The results demonstrated that AlP intoxication causes cardiac toxicity presenting with changes in ECG patterns such as decrement of HR, BP and abnormal QRS complexes, QTc and ST height. T3 at a dose of 3 μg/kg significantly improved ECG and also oxidative stress parameters. Furthermore, T3 administration could increase mitochondrial function and ATP levels within the cardiac cells. In addition, administration of T3 showed a reduction in apoptosis through diminishing the caspase activities and improving cell viability.
  
  
  CONCLUSIONS
  Overall, the present data demonstrate the beneficial effects of T3 in cardiotoxicity of AlP.
authors.affiliation: Department of Pharmacology, School of Medicine, International Campus, Tehran University of Medical Sciences (TUMS-IC), 1417653861 Tehran, Iran; Pharmacology and Applied Medicine, Department of Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, 141554364 Karaj, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 1417614411 Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors.forename: Amir Hossein
authors.initials: AH
authors.lastname: Abdolghaffari
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Baghaei
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Solgi
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, 1417614411 Tehran, Iran; Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, 1417614411 Tehran, Iran.
authors.forename: Maziar
authors.initials: M
authors.lastname: Gooshe
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Baeeri
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors.forename: Mona
authors.initials: M
authors.lastname: Navaei-Nigjeh
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors.forename: Shokoufeh
authors.initials: S
authors.lastname: Hassani
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Jafari
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 1417614411 Tehran, Iran; Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch & Pharmaceutical Sciences Research Center, Islamic Azad University (IAUPS), 194193311 Tehran, Iran.
authors.forename: Seyed Mehdi
authors.initials: SM
authors.lastname: Rezayat
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 1417614411 Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, 1417614411 Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 1417614411 Tehran, Iran.
authors.forename: Shahram Ejtemaei
authors.initials: SE
authors.lastname: Mehr
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran; International Campus, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Endocrinology & Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Mohammad@TUMS.Ac.Ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D017607:Aluminum Compounds / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010575:Pesticides / Q000633:toxicity*; D010720:Phosphines / Q000633:toxicity*; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000627:therapeutic use*
chemical_list: D017607:Aluminum Compounds; D002316:Cardiotonic Agents; D010575:Pesticides; D010720:Phosphines; D014284:Triiodothyronine; C001864:aluminum phosphide
keywords: Aluminum phosphide; Apoptosis; Mitochondrial toxicity; Oxidative stress; Phosphine gas (PH(3)); Triiodothyronine