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姜黄素通过抑制氧化应激、预防炎症和细胞凋亡减轻阿霉素诱导的心脏毒性:超微结构和计算方法

Curcumin attenuates doxorubicin-induced cardiotoxicity suppressing oxidative Stress, preventing inflammation and apoptosis: Ultrastructural and computational approaches.

作者信息

Shati Ayed A, Eid Refaat A, El-Kott Attalla F, Alqahtani Youssef A, Shatoor Abdullah S, Ahmed Zaki Mohamed Samir

机构信息

Department of Child Health, College of Medicine, King Khalid University, Abha, Saudi Arabia.

Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia.

出版信息

Heliyon. 2024 Feb 27;10(5):e27164. doi: 10.1016/j.heliyon.2024.e27164. eCollection 2024 Mar 15.

Abstract

Currently, doxorubicin (DOX) is one of the medications commonly used in chemotherapy to treat different types of tumors.Nonetheless, despite being effective in multiple tumors, yet its use is limited owing to its cytotoxic effects, the therapeutic use of DOX has been limited. This work aimed to explore whether curcumin (CMN) can prevents DOX-induced cardiotoxicity in rats. Four groups of rats were created, with the first functioning as a control, while the second group received CMN. DOX alone was administered to the third group, whereas CMN and DOX were administered to the fourth group. Lipid peroxidation assessed as Malondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), oxidative stress markers as catalase (CAT), superoxide dismutase (SOD), and inflammatory markers as tumor necrosis factor-alpha (TNF-α) in heart homogenates, each one was assessed. Heart specimens was investigated histologically and ultrastructurally. Increased, AST, and ALT serum levels, increased MDA levels, decreased SOD and CAT levels, and increased TNF-α concentrations in heart homogenates were all signs of DOX-induced myocardial injury. Histological and ultrastructural examinations revealed vacuoles and larger, swollen mitochondria in the cytoplasm. Furthermore, DOX caused significant changes in the myocardium, most notably nuclei disintegration, myofibrillar loss, and myocyte vacuolization. Using CMN with DOX reduced the harmful consequences of DOX on the myocardium by returning the increased AST and ALT levels to their original levels as compared to the control and reducing them. In cardiac tissue, CMN significantly increased the concentrations of SOD and CAT and significantly decreased the concentrations of MDA and TNF-α. Biochemical and histological studies have demonstrated that CMN has a heart-protective effect that might be related to its antioxidant and anti-inflammatory capabilities.

摘要

目前,阿霉素(DOX)是化疗中常用于治疗不同类型肿瘤的药物之一。尽管如此,尽管它对多种肿瘤有效,但由于其细胞毒性作用,DOX的治疗用途受到限制。这项工作旨在探讨姜黄素(CMN)是否能预防DOX诱导的大鼠心脏毒性。将大鼠分为四组,第一组作为对照组,第二组接受CMN。第三组单独给予DOX,而第四组给予CMN和DOX。评估了心脏匀浆中作为丙二醛(MDA)的脂质过氧化、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、作为过氧化氢酶(CAT)和超氧化物歧化酶(SOD)的氧化应激标志物以及作为肿瘤坏死因子-α(TNF-α)的炎症标志物。对心脏标本进行了组织学和超微结构研究。血清AST和ALT水平升高、MDA水平升高、SOD和CAT水平降低以及心脏匀浆中TNF-α浓度升高均是DOX诱导心肌损伤的迹象。组织学和超微结构检查显示细胞质中有空泡和更大、肿胀的线粒体。此外,DOX引起心肌显著变化,最明显的是细胞核解体、肌原纤维丧失和心肌细胞空泡化。与DOX联合使用CMN可使升高的AST和ALT水平恢复到与对照组相比的原始水平,并降低其水平,从而减少DOX对心肌的有害影响。在心脏组织中,CMN显著提高了SOD和CAT的浓度,并显著降低了MDA和TNF-α的浓度。生化和组织学研究表明,CMN具有心脏保护作用,这可能与其抗氧化和抗炎能力有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4b9/10926088/0aa2cbad1e80/gr1.jpg

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