Assessment of trazodone-induced cardiotoxicity after repeated doses in rats

Abstract

<jats:p> Trazodone (TRZ) is an antidepressant drug commonly used in the treatment of depression, anxiety, and insomnia. Although some studies demonstrated the adverse effects of TRZ related to cardiovascular system, the conflicting results were observed in these studies. Therefore, we aimed to investigate the cardiac adverse effects of TRZ in rats at repeated doses in our study. In accordance with this purpose, TRZ was administered orally to rats at 5, 10, and 20 mg/kg doses for 28 days. Electrocardiogram records, serum aspartate aminotransferase (AST), lactate dehydrogenase, creatine kinase-myoglobin band, cardiac troponin-T (cTn-T) levels, DNA damage in cardiomyocytes, and histologic view of heart tissues were evaluated. In addition, glutathione (GSH) and malondialdehyde (MDA) levels were measured to determine the oxidative status of cardiac tissue after TRZ administration. Heart rate was decreased, PR interval was prolonged, and QRS and T amplitudes were decreased in 20 mg/kg TRZ-administered group compared to the control group. Serum AST and cTn-T levels were significantly increased in 10 and 20 mg/kg TRZ-administered rats with respect to control rats. DNA damage was significantly increased in these groups. Additionally, degenerative histopathologic findings were observed in TRZ-administered groups. Although there was no difference in MDA levels between groups, GSH levels were significantly decreased in 10 and 20 mg/kg TRZ-administered groups compared to the control group. Our results have shown that TRZ induced cardiotoxicity in rats dose-dependently. It is assumed that oxidative stress related to GSH depletion may be accompanied by these adverse effects. </jats:p>

l-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress

“…The current investigation found that TRZ administration elevated serum CK-MB, AST, and cTnI levels, as well as a substantial increase in cardiac necrosis and myolysis in rat hearts. Previous studies support our findings that TRZ treatment induces myocardial ischemia [ 1 , 28 ].…”

“…TRZ causes a reduction in heart rate, a longer PR interval, and smaller QRS and T amplitudes. In addition, serum AST and cTn-T levels were considerably higher than in the control group [1,13].…”

“…Trazodone can also cause drug-induced long QT syndrome, which can cause life-threatening cardiac arrhythmias in persons with mutations in cardiac ionic channel genes [ 25 ]. TRZ prolonged PR interval has also been linked to hypertrophy and other structural abnormalities like as cardiomyopathy [ 1 ].…”

“…TRZ causes a reduction in heart rate, a longer PR interval, and smaller QRS and T amplitudes. In addition, serum AST and cTn-T levels were considerably higher than in the control group [ 1 , 13 ]. LC ( l carnitine) group Rats received oral dose of l -carnitine (200 mg/kg BW/day) for 28 days.…”

“…Trazodone (TRZ) is a serotonin receptor type 2 (5-HT2) antagonist and reuptake inhibitor that has been clinically approved since 2001. Despite the fact that TRZ is a pharmacologically approved treatment for insomnia, it has a long list of documented side effects, including headaches, dizziness, hypotension, syncope, and feeling off balance problems [ 1 ]. Also, previous studies reported cardiovascular adverse effects such as electrocardiogram (ECG) irregularities (prolonged PR interval & long QT syndrome), postural hypotension, and cardiac arrhythmias were induced at therapeutic and even subtherapeutic doses of TRZ [ 2 ].…”