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Cardioprotective Effect of Paricalcitol on Amitriptyline-Induced Cardiotoxicity in Rats: Comparison of [99mTc]PYP Cardiac Scintigraphy with Electrocardiographic and Biochemical Findings

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Abstract

Taking an overdose of AMT, a commonly prescribed tricyclic antidepressant drug, has an increased risk of sudden cardiac death. The cardiotoxicity of amitriptyline (AMT) is a commonly observed toxicity with high morbidity and mortality rates in emergency departments (ED). Nevertheless, there are still no effective treatment options for AMT-induced cardiotoxicity. The aim of the present study was to evaluate the effects of paricalcitol (PRC), a Vitamin D receptor agonist, using electrocardiographic (ECG), biochemical, and scintigraphic methods. Twenty-eight male Wistar rats were randomly divided into four groups: untreated control (CON), amitriptyline-induced cardiotoxicity (AMT), paricalcitol (PRC), and amitriptyline + paricalcitol (AMT + PRC). Cardiotoxicity was induced by intraperitoneal (i.p) injection of a single-dose AMT (100 mg/kg). PRC was administered as 10 μg/kg (i.p.) after the injection of AMT. We examined ECG, biochemical, and scintigraphic results of PRC administration on AMT-induced changes. Cardiotoxicity of AMT was characterized by conduction abnormalities (increased QRS complex, T wave, and QT interval duration and elevation of ST segment amplitude), elevated 99mTechnetium Pyrophosphate ([99mTc]PYP) uptake, and increased cardiac troponin T (cTnT) levels. Treatment with PRC significantly decreased all AMT-associated conduction abnormalities in ECG (p < 0.001), and decreased [99mTc]PYP uptake (p < 0.001) and serum cTnT level (p < 0.001). The present study indicated that the vitamin D receptor agonist paricalcitol could decrease the AMT-induced cardiotoxicity. This suggests [99mTc]PYP as a non-invasive method for the evaluation of myocardial injury induced by AMT. According to the results of the present study, PRC has beneficial effects on AMT-induced cardiotoxicity.

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  1. Department of Physiology, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, 60030, Turkey

    Hatice Aygun

  2. Department of Emergency Medicine, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, Turkey

    Nursah Basol

  3. Department of Nuclear Medicine, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, Turkey

    Serdar Savas Gul

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  1. Hatice Aygun
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HA: designing the research concept. HA, NB, and SSG: conducting experiments, collecting data, analyzing, and interpreting the data. HA: preparing the manuscript and making revisions. All authors read and approved the final version of the manuscript.

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Aygun, H., Basol, N. & Gul, S.S. Cardioprotective Effect of Paricalcitol on Amitriptyline-Induced Cardiotoxicity in Rats: Comparison of [99mTc]PYP Cardiac Scintigraphy with Electrocardiographic and Biochemical Findings. Cardiovasc Toxicol 20, 427–436 (2020). https://doi.org/10.1007/s12012-020-09569-3

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