Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Drug Res (Stuttg). 2021 Apr;71(4):219-227. doi: 10.1055/a-1308-1585. Epub 2020 Dec 4.
The possible action of polyphenolic compounds in the reduction of reactive oxygen species (ROS) and mitochondrial toxicity may suggest them as putative agents for the treatment of drug-induced mitochondrial dysfunction and cardiotoxicity. This study was designed to explore protective effect of ellagic acid (EA) against celecoxib-induced cellular and mitochondrial toxicity in cardiomyocytes and their isolated mitochondria. In order to do this, isolated cardiomyocytes and mitochondria were pretreated with 3 different concentrations of EA (10, 50 and 100 µM), after which celecoxib (16 µg/ml) was added to promote deleterious effects on cells and mitochondria. Using flow cytometry and biochemical methods, the parameters of cellular and mitochondrial toxicity were investigated. Our results showed that celecoxib (16 µg/ml) caused a significant decrease in cell viability, mitochondrial membrane potential (MMP), glutathione (GSH) in intact cardiomyocytes and succinate dehydrogenase (SDH) activity, MMP collapse, and mitochondrial swelling, and a significant increase in reactive oxygen species (ROS) formation, lipid peroxidation (LP) and oxidative stress in isolated mitochondria. Also, our results revealed that co-administration of EA (50 and 100 µM) with celecoxib significantly attenuated the cellular and mitochondrial toxicity effects. In this study, we showed that simultaneous treatment with of EA ameliorated the cellular and mitochondrial toxicity induced by celecoxib, with cardiomyocytes presenting normal activity compared to the control group, and mitochondria retaining their normal activity.
多酚化合物在减少活性氧（ROS）和线粒体毒性方面的可能作用表明它们可能是治疗药物诱导的线粒体功能障碍和心脏毒性的潜在药物。本研究旨在探讨鞣花酸（EA）对塞来昔布诱导的心肌细胞及其分离的线粒体细胞和线粒体毒性的保护作用。为此，将分离的心肌细胞和线粒体用 3 种不同浓度的 EA（10、50 和 100µM）预处理，然后加入塞来昔布（16µg/ml）以促进对细胞和线粒体的有害影响。使用流式细胞术和生化方法研究了细胞毒性和线粒体毒性的参数。结果表明，塞来昔布（16µg/ml）显著降低了完整心肌细胞的细胞活力、线粒体膜电位（MMP）、谷胱甘肽（GSH）、琥珀酸脱氢酶（SDH）活性、MMP 崩溃和线粒体肿胀，以及活性氧（ROS）形成、脂质过氧化（LP）和分离线粒体中的氧化应激显著增加。此外，我们的结果还表明，EA（50 和 100µM）与塞来昔布同时给药可显著减轻细胞毒性和线粒体毒性作用。在这项研究中，我们表明，同时用 EA 治疗可改善塞来昔布诱导的细胞毒性和线粒体毒性，与对照组相比，心肌细胞呈现正常活性，线粒体保持正常活性。
