Atli O, Kilic V, Baysal M, Kilic G, Gormus G, Ucarcan S, Korkut B, Ilgin S
1 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey.
2 Department of Biology, Faculty of Science, Anadolu University, Eskisehir, Turkey.
Hum Exp Toxicol. 2019 Jan;38(1):45-55. doi: 10.1177/0960327118769717. Epub 2018 May 18.
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.
曲唑酮（TRZ）是一种常用于治疗抑郁症、焦虑症和失眠症的抗抑郁药物。尽管一些研究表明TRZ对心血管系统有不良影响，但这些研究结果相互矛盾。因此，在本研究中，我们旨在研究重复给药剂量下TRZ对大鼠心脏的不良影响。按照这一目的，以5、10和20mg/kg的剂量给大鼠口服TRZ，持续28天。评估心电图记录、血清天冬氨酸转氨酶（AST）、乳酸脱氢酶、肌酸激酶-肌红蛋白条带、心肌肌钙蛋白T（cTn-T）水平、心肌细胞中的DNA损伤以及心脏组织的组织学观察结果。此外，测量谷胱甘肽（GSH）和丙二醛（MDA）水平，以确定TRZ给药后心脏组织的氧化状态。与对照组相比，20mg/kg TRZ给药组的心率降低，PR间期延长，QRS波和T波振幅降低。与对照大鼠相比，10mg/kg和20mg/kg TRZ给药大鼠的血清AST和cTn-T水平显著升高。这些组中的DNA损伤显著增加。此外，在TRZ给药组中观察到退行性组织病理学结果。尽管各组之间MDA水平没有差异，但与对照组相比，10mg/kg和20mg/kg TRZ给药组的GSH水平显著降低。我们的结果表明，TRZ在大鼠中剂量依赖性地诱导心脏毒性。推测与GSH消耗相关的氧化应激可能伴随着这些不良反应。
