Department of Pharmacology and Toxicology, School of Pharmacy, 48413Ardabil University of Medical Sciences, Ardabil, Iran.
Traditional Medicine and Hydrotherapy Research Center, 48413Ardabil University of Medical Sciences, Ardabil, Iran.
Hum Exp Toxicol. 2021 Dec;40(12_suppl):S530-S539. doi: 10.1177/09603271211053299. Epub 2021 Oct 29.
Mitochondria are the main target organelles through which drugs and chemicals exert their toxic effect on cardiomyocytes. The mitochondria-related mechanisms of celecoxib-induced cardiotoxicity have been extensively studied. Accumulated evidence shows natural molecules targeting mitochondria have proven to be effective in preventing cardiotoxicity.
In the present study, we examined the ameliorative effect of gallic acid (GA) against celecoxib-induced cellular and mitochondrial toxicity in isolated cardiomyocytes and mitochondria.
The isolated cardiomyocytes and mitochondria were divided into various group, namely, control, celecoxib, celecoxib + GA (10, 50, and 100 µM). Several cellular and mitochondrial parameters such as cell viability, lipid peroxidation, succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling were assessed in isolated cardiomyocytes and mitochondria.
Our results showed that administration of celecoxib (16 µg/ml) induced cytotoxicity and mitochondrial dysfunction at 6 h and 1 h, respectively, which is associated with lipid peroxidation intact cardiomyocytes, mitochondrial ROS formation, MMP collapse, and mitochondrial swelling. The cardiomyocytes and mitochondria treated with celecoxib + GA (10, 50, and 100 µM) significantly and dose-dependently restore the altered levels of cellular and mitochondrial parameters.
We concluded that GA through antioxidant potential and inhibition of mitochondrial permeability transition (MPT) pore exerted ameliorative role in celecoxib-induced toxicity in isolated cardiomyocytes and mitochondria. The data of the current study suggested that GA supplementation may reduce celecoxib-induced cellular and mitochondrial toxicity during exposure and may provide a potential prophylactic and defensive candidate for coxibs-induced mitochondrial dysfunction, oxidative stress, and cardiotoxicity.
线粒体是药物和化学物质对心肌细胞发挥毒性作用的主要靶细胞器。塞来昔布诱导的心脏毒性的线粒体相关机制已得到广泛研究。越来越多的证据表明，靶向线粒体的天然分子已被证明可有效预防心脏毒性。
本研究旨在探讨没食子酸（GA）对分离的心肌细胞和线粒体中塞来昔布诱导的细胞和线粒体毒性的改善作用。
将分离的心肌细胞和线粒体分为对照组、塞来昔布组、塞来昔布+GA（10、50 和 100μM）组。评估了分离的心肌细胞和线粒体中的细胞活力、脂质过氧化、琥珀酸脱氢酶（SDH）活性、活性氧（ROS）形成、线粒体膜电位（MMP）崩溃和线粒体肿胀等多种细胞和线粒体参数。
结果表明，给予塞来昔布（16μg/ml）可在 6 小时和 1 小时分别诱导细胞毒性和线粒体功能障碍，与完整的心肌细胞脂质过氧化、线粒体 ROS 形成、MMP 崩溃和线粒体肿胀有关。用塞来昔布+GA（10、50 和 100μM）处理的心肌细胞和线粒体可显著和剂量依赖性地恢复改变的细胞和线粒体参数水平。
GA 通过抗氧化潜力和抑制线粒体通透性转换（MPT）孔，在分离的心肌细胞和线粒体中发挥了对塞来昔布诱导的毒性的改善作用。本研究的数据表明，GA 补充可能会减少暴露过程中塞来昔布引起的细胞和线粒体毒性，并为 COXIB 诱导的线粒体功能障碍、氧化应激和心脏毒性提供潜在的预防和防御候选物。
