Molecular and Biochemical Evidences on the Protective Effects of Triiodothyronine Against Phosphine-Induced Cardiac and Mitochondrial Toxicity Publisher Pubmed



Abdolghaffari AH^{1, 2, 3, 4} ; Baghaei A⁴ ; Solgi R⁴ ; Gooshe M^{5, 6} ; Baeeri M⁴ ; Navaeinigjeh M⁴ ; Hassani S⁴ ; Jafari A⁴ ; Rezayat SM^{3, 7} ; Dehpour AR^{3, 5} ; Mehr SE³ ; Abdollahi M^{4, 8, 9} Show Affiliations
Source: Life Sciences Published:2015

Abstract

Aim: 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. Main 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, 24 h 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. Key findings: 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. Significance: Overall, the present data demonstrate the beneficial effects of T3 in cardiotoxicity of AlP. © 2015 Elsevier Inc. All rights reserved.