Al-Kuraishy Hayder M, Al-Gareeb Ali I, Alkhuriji Afrah Fahad, Al-Megrin Wafa Abdullah I, Elekhnawy Engy, Negm Walaa A, De Waard Michel, Batiha Gaber El-Saber
Department of Clinical Pharmacology and Medicine, College of Medicine, Al-mustansiriyiah University, Iraq.
Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Biomed Pharmacother. 2022 Oct;154:113673. doi: 10.1016/j.biopha.2022.113673. Epub 2022 Sep 7.
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.
心脏损伤是阿霉素（Dox）作为抗癌药物使用时的主要剂量限制因素。阿霉素的心脏毒性与多种复杂机制有关，包括氧化应激、线粒体损伤、细胞内钙失调以及细胞凋亡/坏死。本研究调查了阿霉素诱导的心脏毒性的几个方面。我们研究了单独或联合使用不同剂量的瑞舒伐他汀和替米沙坦预处理对阿霉素诱导的急性心脏毒性的影响。本研究结果表明，阿霉素可诱导心肌细胞发生显著的病理变化。在与心脏损伤相关的几种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）、炎症过程如白细胞介素-17（IL-17）方面观察到不良反应，并伴有重要的组织病理学变化。我们阐述了这两种药物对阿霉素急性心脏毒性的心脏保护作用。这表现为生物标志物水平的显著改善以及相关的组织学损伤。本研究指出，单独或联合使用瑞舒伐他汀和替米沙坦作为一种临床选择，对于降低阿霉素对心肌细胞的急性毒性有益。
