Department of Biochemistry, Faculty of Pharmacy, Tanta University, Al-Baher Street, Medical Campus, Tanta, 31527, Egypt.
Clinical Pharmacy & Pharmacy Practice Department, Faculty of Pharmacy, Damanhur University, El-Bahiara, Egypt.
Cardiovasc Toxicol. 2022 Sep;22(9):831-841. doi: 10.1007/s12012-022-09759-1. Epub 2022 Jul 4.
Trazodone (TRZ) is an antidepressant drug which widely used to treat insomnia, but it has a cardiotoxic effect which considered one of the TRZ limitations. The aim of this study was to investigate the protective role of L-carnitine in rats against TRZ-induced cardiotoxicity, as well as to look into the molecular mechanisms underlying its cardioprotective effects via autophagy-mediated cell death and oxidative stress. Male albino rats were randomized into four experimental groups (n = 8): normal control, TRZ group (TRZ, 20 mg/kg/day), L-carnitine group (LC, 200 mg/kg/day), and Co-treated group (L-carnitine and TRZ). All treatments were administered via oral gavage for 4 weeks. Cardiac enzymes (AST & CK-MB) and serum cardiac troponin T(cTnI) were assessed. Oxidative stress biomarkers in heart tissue (malondialdehyde; MDA, total thiol, and catalase activity) were measured. Autophagy related-genes (ATG-5 and Beclin-1), P62, and TNF-α were quantified. AST and CK-MB and cTnI significantly (p < 0.001) were increased with enhanced autophagy as well as severe histopathological changes which were manifested as scattered chronic inflammatory cells with focal fragmentation of myocardial fibers and loss of nuclei in TRZ-treated group. However, daily administration of L-carnitine (200 mg/kg) for 28 days completely reversed TRZ-induced the increased cardiac enzymes, autophagy, and myocardial inflammatory processes to the normal values. TRZ administration might have the potential to cause cardiotoxic effects that can be treated with L-carnitine administration.
曲唑酮（TRZ）是一种抗抑郁药，广泛用于治疗失眠，但它具有心脏毒性作用，这被认为是 TRZ 的限制之一。本研究旨在研究左旋肉碱（L-carnitine）对大鼠 TRZ 诱导的心脏毒性的保护作用，并探讨其通过自噬介导的细胞死亡和氧化应激发挥心脏保护作用的分子机制。雄性白化大鼠随机分为四组（每组 8 只）：正常对照组、TRZ 组（TRZ，20mg/kg/天）、L-肉碱组（LC，200mg/kg/天）和联合治疗组（L-肉碱和 TRZ）。所有治疗均通过口服灌胃进行，持续 4 周。检测心脏酶（AST 和 CK-MB）和血清心肌肌钙蛋白 T（cTnI）。测定心脏组织的氧化应激生物标志物（丙二醛；MDA、总巯基和过氧化氢酶活性）。定量自噬相关基因（ATG-5 和 Beclin-1）、P62 和 TNF-α。AST 和 CK-MB 和 cTnI 显著增加（p<0.001），同时自噬增强，以及心肌纤维局灶性慢性炎症细胞散在和心肌纤维局灶性碎裂，细胞核丢失等严重的组织病理学变化，这些变化在 TRZ 治疗组中表现明显。然而，每天给予 200mg/kg 的 L-肉碱治疗 28 天可完全逆转 TRZ 诱导的心脏酶、自噬和心肌炎症过程，使其恢复正常。TRZ 给药可能有引起心脏毒性的潜力，可以通过给予 L-肉碱来治疗。
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