Kabel Ahmed M, Salama Samir A, Adwas Almokhtar A, Estfanous Remon S
Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.
Division of Biochemistry, Department of Pharmacology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Pharmaceuticals (Basel). 2021 Nov 20;14(11):1188. doi: 10.3390/ph14111188.
Doxorubicin belongs to the class of anthracycline antibiotics that is widely used in the treatment protocols of a wide range of malignancies. The major deleterious effect of doxorubicin use is the possible occurrence of cardiotoxicity. This study aimed to delineate the possible effects of targeting oxidative stress, NLRP3 inflammasome, and autophagy by fraxetin on doxorubicin-induced cardiac dysfunction in rats. In a model of doxorubicin-induced cardiotoxicity, the effects of different doses of fraxetin were assessed by determination of biochemical, histopathological, immunohistochemical, and electron microscopic changes. Fraxetin, in a dose-dependent manner, was found to have the ability to mitigate the harmful effects of oxidative stress and inflammation on myocardial muscles with significant decrease in NLRP3 inflammasome, augmentation of autophagy, and amelioration of the apoptotic signaling pathways. In addition, fraxetin, in a dose-dependent manner, had the ability to combat the echocardiographic, histopathological, immunohistochemical, and electron microscopic changes induced by doxorubicin in cardiomyocytes. As a result, fraxetin may be put into consideration as a new adjuvant line of therapy on the way to mitigate doxorubicin-induced cardiotoxicity.
阿霉素属于蒽环类抗生素，广泛应用于多种恶性肿瘤的治疗方案中。使用阿霉素的主要有害影响是可能发生心脏毒性。本研究旨在阐明白蜡素靶向氧化应激、NLRP3炎性小体和自噬对阿霉素诱导的大鼠心脏功能障碍可能产生的影响。在阿霉素诱导的心脏毒性模型中，通过测定生化、组织病理学、免疫组织化学和电子显微镜变化来评估不同剂量白蜡素的作用。发现白蜡素能够以剂量依赖的方式减轻氧化应激和炎症对心肌的有害影响，NLRP3炎性小体显著减少，自噬增强，凋亡信号通路改善。此外，白蜡素能够以剂量依赖的方式对抗阿霉素诱导的心肌细胞超声心动图、组织病理学、免疫组织化学和电子显微镜变化。因此，在减轻阿霉素诱导的心脏毒性方面，白蜡素可被视为一种新的辅助治疗方法。
