Molecular and biochemical evidences on the protective effects of triiodothyronine against phosphine-induced cardiac and mitochondrial toxicity

AimAluminum 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 methodsIn 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 findingsThe 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.SignificanceOverall, the present data demonstrate the beneficial effects of T3 in cardiotoxicity of AlP.

Proposed mechanism of the cardioprotective effects of T3 on AlP toxicity at the cellular level.AlP: aluminum phosphide, PH3: phosphine gas, T3: triiodothyronine, ECG: electrocardiogram, HR: heart rate, BP: blood pressure, ATP: adenosine triphosphate, ROS: reactive oxygen species, SOD: superoxide dismutase, LPO: lipid peroxidation.104