Salimi Ahmad, Bahreini Farnaz, Jamali Zhaleh, Pourahmad Jalal
Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Int J Toxicol. 2020 May/Jun;39(3):241-247. doi: 10.1177/1091581820918163. Epub 2020 Apr 20.
Mesalazine is widely used in the management of inflammatory bowel disease. Previous studies reported that mesalazine-induced cardiotoxicity is a rare, potentially fatal complication. Mitochondria play an important role in myocardial tissue homeostasis. Deterioration in mitochondrial function will eventually lead to cardiomyocyte death and consequently cardiovascular dysfunction. The aim of the current study was to investigate the effects of mesalazine on rat heart mitochondria. Rat heart mitochondria were isolated by mechanical lysis and differential centrifugation. Parameters of mitochondrial toxicity including succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release were evaluated. Results revealed that mesalazine induced a concentration- and time-dependent rise in mitochondrial ROS formation, inhibition of SDH, MMP collapse, mitochondrial swelling, and cytochrome c release in rat heart mitochondria. These results indicate that the cardiotoxic effects of mesalazine are most likely associated with mitochondrial dysfunction and ROS formation, which finally ends in cytochrome c release signaling and induction of apoptosis.
美沙拉嗪广泛用于炎症性肠病的治疗。先前的研究报道，美沙拉嗪诱导的心脏毒性是一种罕见的、潜在致命的并发症。线粒体在心肌组织稳态中起重要作用。线粒体功能的恶化最终将导致心肌细胞死亡，进而导致心血管功能障碍。本研究的目的是探讨美沙拉嗪对大鼠心脏线粒体的影响。通过机械裂解和差速离心分离大鼠心脏线粒体。评估线粒体毒性参数，包括琥珀酸脱氢酶（SDH）活性、活性氧（ROS）生成、线粒体膜电位（MMP）崩溃、线粒体肿胀和细胞色素c释放。结果显示，美沙拉嗪诱导大鼠心脏线粒体中ROS生成、SDH抑制、MMP崩溃、线粒体肿胀和细胞色素c释放呈浓度和时间依赖性增加。这些结果表明，美沙拉嗪的心脏毒性作用很可能与线粒体功能障碍和ROS生成有关，最终导致细胞色素c释放信号和凋亡诱导。
