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


Aygun H., Basol N., Gul S. S.

Cardiovascular Toxicology, vol.20, no.4, pp.427-436, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 20 Issue: 4
  • Publication Date: 2020
  • Doi Number: 10.1007/s12012-020-09569-3
  • Title of Journal : Cardiovascular Toxicology
  • Page Numbers: pp.427-436
  • Keywords: Amitriptyline, Cardiotoxicity, ECG, Paricalcitol, (99m)tc pyrophosphate, ACUTE MYOCARDIAL-INFARCTION, INDUCED CARDIOVASCULAR TOXICITY, D-RECEPTOR ACTIVATORS, VITAMIN-D ANALOGS, 1,25-DIHYDROXYVITAMIN D-3, SKELETAL-MUSCLE, HEART-FAILURE, CALCIUM, ANTIDEPRESSANTS, CARDIOMYOPATHY

Abstract

© 2020, Springer Science+Business Media, LLC, part of Springer Nature.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.