Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Cell Biochem Funct. 2023 Jun;41(4):450-460. doi: 10.1002/cbf.3795. Epub 2023 Apr 12.
The cardiotoxic effect of chemotherapeutic agents as cisplatin has become a major issue recently. Interference with mitochondrial dynamics, biogenesis, redox status, and apoptosis are the most possible underlying mechanisms. Semaglutide is a human glucagon-like peptide-1 receptor agonist (GLP-1R), which is used primarily for the treatment of DM. Various recent studies have investigated (GLP-1R) role in cardiovascular diseases due to antiapoptotic and antioxidant effects. The current study aimed to investigate the curative role of semaglutide's against cisplatin- induced cardiotoxicity and its relation to mitochondrial functions, dynamics, biogenesis, apoptosis, and redox status pathways. The study included 30 male rats divided into three groups: control, cisplatin-induced cardiotoxicity, and cisplatin-induced cardiotoxicity treated with semaglutide. At the end of the experiment heart index, serum cardiotoxicity markers, SOD, GPX activities and H O level were estimated. Mitochondrial transmembrane potential, complex I and citrate synthase enzyme activities, ATP level, Mfn2 in addition to PGC-1 α levels were assessed as biogenesis markers. Mitophagy markers PINK1 and Parkin mRNA gene expression were estimated. Histopathological examination of cardiac muscles of all studied groups and immunoassay of P53 and caspase 3 in cardiac tissue were examined to assess apoptosis. Cisplatin has disturbed mitochondrial function and dynamics, dysregulate redox status and induced mitophagy and apoptosis, in the other hand semaglutide treatment has normalized dysregulated mitochondrial function and dynamics, redox status and suppressed mitophagy and apoptosis. Semaglutide has ameliorative effect against cisplatin- induced cardiotoxicity via modulation of mitochondrial functions, dynamics, biogenesis, apoptosis, and redox status pathways.
化疗药物如顺铂的心脏毒性作用最近成为一个主要问题。干扰线粒体动力学、生物发生、氧化还原状态和细胞凋亡是最可能的潜在机制。司美格鲁肽是一种人胰高血糖素样肽-1 受体激动剂（GLP-1R），主要用于治疗糖尿病。由于具有抗细胞凋亡和抗氧化作用，最近的各种研究调查了（GLP-1R）在心血管疾病中的作用。本研究旨在探讨司美格鲁肽对顺铂诱导的心肌毒性的治疗作用及其与线粒体功能、动力学、生物发生、细胞凋亡和氧化还原状态途径的关系。该研究包括 30 只雄性大鼠，分为三组：对照组、顺铂诱导的心肌毒性组和用司美格鲁肽治疗的顺铂诱导的心肌毒性组。实验结束时，评估了心脏指数、血清心肌毒性标志物、SOD、GPX 活性和 H2O2 水平。评估了线粒体跨膜电位、复合物 I 和柠檬酸合酶酶活性、ATP 水平、作为生物发生标志物的 Mfn2 以及 PGC-1α 水平。估计了自噬标志物 PINK1 和 Parkin mRNA 基因表达。检查了所有研究组的心肌组织的组织病理学检查和心脏组织中 P53 和 caspase 3 的免疫测定，以评估细胞凋亡。顺铂扰乱了线粒体功能和动力学，使氧化还原状态失调并诱导自噬和细胞凋亡，另一方面，司美格鲁肽治疗使失调的线粒体功能和动力学、氧化还原状态正常化，并抑制自噬和细胞凋亡。司美格鲁肽通过调节线粒体功能、动力学、生物发生、细胞凋亡和氧化还原状态途径对顺铂诱导的心肌毒性具有改善作用。
