College of Pharmacy, Xinxiang Medical University, Xinxiang, China.
Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, China.
J Biochem Mol Toxicol. 2022 Mar;36(3):e22971. doi: 10.1002/jbt.22971. Epub 2021 Nov 23.
The medical usage of Doxorubicin (DOX) as a chemotherapeutic agent is restricted owing to its cardiotoxic properties. This study was designed to explore the effect and underlying mechanisms of Citronellal (CT) on DOX-related cardiotoxicity in rats. Rats were divided into six groups: control, DOX, CT, Lithium chloride (LiCl) (a Na+/H+exchanger-1 [NHE1] activator), DOX + CT, and DOX + CT + LiCl. To induce cardiotoxicity, a cumulative dose of 15 mg/kg DOX was intraperitoneally injected into rats. CT (150 mg/kg) and LiCl (1 mg/kg) were given daily by oral gavage for 6 weeks. CT improved cardiac functional parameters and attenuated the cardiac pathological changes induced by DOX. Further study indicated that CT administration regulated the levels of oxidative stress and apoptosis-related factors and in myocardial tissues, reducing cell per-oxidative damage and apoptosis. Besides this, CT attenuated DOX-induced NHE1 upregulation, and the preventive effects of CT against DOX-induced cardiotoxicity were abrogated by the concurrent administration of LiCl. These results demonstrate that CT could ameliorate DOX-induced cardiotoxicity by inhibiting the NHE1-mediated oxidative stress, apoptosis in rats.
阿霉素（DOX）作为一种化疗药物，由于其心脏毒性而受到限制。本研究旨在探讨香茅醛（CT）对大鼠 DOX 相关心脏毒性的作用及其潜在机制。大鼠分为六组：对照组、DOX 组、CT 组、氯化锂（LiCl）（Na+/H+交换器-1 [NHE1] 激活剂）组、DOX+CT 组和 DOX+CT+LiCl 组。为了诱导心脏毒性，大鼠腹腔内注射累积剂量为 15mg/kg 的 DOX。CT（150mg/kg）和 LiCl（1mg/kg）每日通过口服灌胃给予 6 周。CT 改善了心脏功能参数，并减轻了 DOX 引起的心脏病理变化。进一步的研究表明，CT 给药调节了氧化应激和凋亡相关因子在心肌组织中的水平，减轻了细胞过氧化损伤和凋亡。此外，CT 减弱了 DOX 诱导的 NHE1 上调，而 LiCl 的同时给药消除了 CT 对 DOX 诱导的心脏毒性的预防作用。这些结果表明，CT 可通过抑制 NHE1 介导的氧化应激、凋亡来改善 DOX 诱导的大鼠心脏毒性。
