Beneficial effects of edaravone in experimental model of amitriptyline-induced cardiotoxicity in rats


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

Naunyn-Schmiedeberg's Archives of Pharmacology, vol.392, no.11, pp.1447-1453, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 392 Issue: 11
  • Publication Date: 2019
  • Doi Number: 10.1007/s00210-019-01683-6
  • Title of Journal : Naunyn-Schmiedeberg's Archives of Pharmacology
  • Page Numbers: pp.1447-1453
  • Keywords: Amitriptyline, Cardiotoxicity, ECG, Edaravone, Rat, Tc-99m-PYP, ACUTE MYOCARDIAL-INFARCTION, FREE-RADICAL SCAVENGER, TROPONIN-I, ANTIDEPRESSANTS, TOXICITY, TL-201, DAMAGE

Abstract

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.Amitriptyline (AMT) cardiotoxicity is commonly seen with high morbidity and mortality rates in emergency departments. Nevertheless, there are still no effective treatment options for amitriptyline-induced cardiotoxicity. The aim of the present study was to evaluate the effects of edaravone, a potent antioxidant and free radical scavenger, in rats by electrocardiographic (ECG), biochemical, and scintigraphic methods. Twenty-eight male Wistar rats were randomly divided into four groups as untreated control (CON), amitriptyline-induced cardiotoxicity (AMT), edaravone treatment (EDO), and amitriptyline + edaravone treatment (AMT+EDO). Cardiotoxicity was induced by intraperitoneal (i.p.) injection of a single-dose amitriptyline (100 mg/kg). Edaravone was administered at a dose of 30 mg/kg (i.p.) after amitriptyline injection. ECG, biochemical, and scintigraphic changes due to edaravone were analyzed. AMT cardiotoxicity was characterized with conduction abnormalities (increased QRS complex, T wave, and duration of QT interval and elevation of ST segment amplitude), elevated 99mTechnetium Pyrophosphate (99mTc-PYP) uptake level, and increased cardiac troponin T level (cTnT). Edaravone treatment significantly decreased all amitriptyline-associated conduction abnormalities in ECG (p < 0.001), 99mTc-PYP uptake (p < 0.001), and serum cTnT level (p < 0.001). 99mTc-PYP scintigraphy can show amitriptyline cardiotoxicity as well as ECG abnormalities and increased values of cTnT. According to the results of the present study, edaravone has strong beneficial effects on amitriptyline-induced cardiotoxicity.