Few studies have reported a prophylactic effect of the anti‐ischemic trimetazidine (TRI) against cardiac toxicity caused by adriamycin (ADR). However, the mechanism of action of TRI remained incomplete. The cardioprotective mechanism(s) of TRI against ADR‐induced cardiotoxicity was investigated in this study. Cardiotoxicity was induced in three groups of Wistar rats by injecting a single dose of ADR (10 mg/kg, i.p.). TRI was administered in two doses regimen, low (L) (2.5 mg/kg, i.p.) and high (H) (10 mg/kg, i.p.). The results of the study showed that both TRI L and H doses improved cardiac enzymes and pathology, while only the TRI H dose improved the electrocardiogram. Both TRI L and H doses decreased malondialdehyde and increased reduced glutathione and superoxide dismutase. Only TRI H dose increased glutathione peroxidase and catalase. Both TRI L and H doses decreased interleukin‐1 beta and tumor necrosis factor‐alpha (TNF‐α). Both TRI L and H doses downregulated TNF‐α, BAX, and vascular endothelial growth factor cardiac protein expression. The data obtained in this study provided evidence that TRI opposed ADR‐induced cardiotoxicity. The mechanism could be due to improved antioxidant levels as well as inhibition of inflammation and programmed cell death.

中文翻译：

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曲美他嗪通过抗氧化机制下调TNF-α，BAX和VEGF免疫表达来改善阿霉素诱导的心肌病

很少有研究报道抗缺血性曲美他嗪（TRI）对由阿霉素（ADR）引起的心脏毒性的预防作用。但是，TRI的作用机制仍然不完整。在这项研究中研究了TRI对抗ADR引起的心脏毒性的心脏保护机制。通过注射单剂量的ADR（10 mg / kg，ip）在三组Wistar大鼠中诱发心脏毒性。TRI分两种剂量给药，低（L）（2.5 mg / kg，ip）和高（H）（10 mg / kg，ip）。研究结果表明，TRI L和H剂量均可改善心脏酶和病理，而只有TRI H剂量可改善心电图。TRI L和H剂量均可降低丙二醛含量，并增加减少的谷胱甘肽和超氧化物歧化酶含量。仅TRI H剂量增加了谷胱甘肽过氧化物酶和过氧化氢酶。TRI L和H剂量均可降低白介素-1β和肿瘤坏死因子-α（TNF-α）。TRI L和H剂量均下调TNF-α，BAX和血管内皮生长因子心脏蛋白的表达。本研究获得的数据提供了TRI对抗ADR引起的心脏毒性的证据。该机制可能归因于抗氧化剂水平的提高以及炎症和程序性细胞死亡的抑制。