心脏损伤是阿霉素（Dox）作为抗癌药物使用的主要剂量限制因素。Dox的心脏毒性与多种复杂机制相关，包括氧化应激、线粒体损伤、细胞内钙离子调节和凋亡/坏死。本研究探讨了Dox诱导的心脏毒性的几个方面。我们研究了罗伊司他汀和替米沙坦预处理对Dox诱导的急性心脏毒性的影响，这些药物以单独或联合的方式使用，并采用不同剂量。本研究结果显示，Dox引起了心肌细胞的明显病理变化。多个与心脏损伤相关的生物标志物（如心肌肌钙蛋白I（cTnI）和乳酸脱氢酶（LDH））、氧化应激（如丙二醛（MDA））和炎症过程（如白细胞介素-17（IL-17））显示不良反应，伴随着重要的组织病理学变化。我们阐述了这两种药物对Dox急性心脏毒性的心肌保护贡献。这表现为生物标志物水平和相关组织学损伤的显着改善。本研究指出罗伊司他汀和替米沙坦单独或联合作为临床选择降低Dox对心肌细胞急性毒性的有益用途。 版权所有© 2022 The Authors。由Elsevier Masson SAS.发表。保留所有权利。

Cardiac injury is the main dose-limiting factor for doxorubicin (Dox) use as an anticancer agent. The cardiotoxicity of Dox is linked to a number of complex mechanisms, including oxidative stress, mitochondrial damage, intracellular calcium dysregulation, and apoptosis/necrosis. This study investigates several aspects of Dox-induced cardiotoxicity. We investigated the effects of pre-treatment with rosuvastatin and telmisartan, which were used in different doses alone or combination, on the acute cardiotoxicity induced by Dox. The results of this study showed that Dox induced significant pathological changes in the cardiomyocytes. Adverse effects were observed on several biomarkers related to cardiac damage like cardiac troponin I (cTnI) and lactate dehydrogenase (LDH), oxidative stress like malondialdehyde (MDA), an inflammatory process like interleukin-17 (IL-17) with important histopathological changes. We illusterate the cardio-protective contribution of the two pharmacological agents against the acute cardiotoxic effects of Dox. This is manifested by the significant improvement in the biomarker levels and the associated histological damage. This study points out the beneficial use of both rosuvastatin and telmisartan alone or in combination as a clinical option for decreasing the acute toxicity of Dox on cardiomyocytes.Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.