Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Feb;397(2):889-897. doi: 10.1007/s00210-023-02648-6. Epub 2023 Aug 1.
It is reported that tramadol can induce neurotoxic effects with the production of DNA damage, mitochondrial dysfunction, and oxidative stress. The current study aimed to evaluate the potential role of mitochondrial impairment in the pathogenesis of tramadol-induced neurotoxicity, and protective effect of sinapic acid (SA) against it in isolated mitochondria from rat brain. Mitochondria were isolated and were incubated with toxic concentrations (100 μM) of tramadol and then cotreated with tramadol + SA (10, 50, and 100 μM). Biomarkers of mitochondrial toxicity including succinate dehydrogenases (SDH) activity, reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), GSH depletion, and mitochondrial swelling were assessed. Our results showed a significant decrease in SDH activity, and a significant increase in ROS, LPO, GSH depletion, MMP collapse, and mitochondrial swelling was detected in tramadol group. We observed that 50 and 100 μM SA cotreatment for 1 h efficiently ameliorated tramadol-caused damage in mitochondrial dysfunction, accumulation of ROS, LPO, GSH depletion, depolarization of mitochondrial membrane potential, and mitochondrial swelling. These data suggest that mitochondrial impairment and oxidative stress are mechanisms involved in the pathogenesis of tramadol-induced neurotoxicity. Also, results indicate that SA antagonizes against tramadol-induced mitochondrial toxicity and suggest SA may be a preventive/therapeutic agent for tramadol-induced neurotoxicity complications.
据报道，曲马多可引起神经毒性作用，导致 DNA 损伤、线粒体功能障碍和氧化应激。本研究旨在评估线粒体损伤在曲马多诱导的神经毒性发病机制中的潜在作用，以及芥子酸（SA）对其的保护作用。分离大鼠脑线粒体并孵育于毒性浓度（100 μM）的曲马多，然后用曲马多+SA（10、50 和 100 μM）进行共处理。评估线粒体毒性的生物标志物，包括琥珀酸脱氢酶（SDH）活性、活性氧（ROS）、脂质过氧化（LPO）、线粒体膜电位（MMP）、GSH 耗竭和线粒体肿胀。结果显示，在曲马多组中，SDH 活性显著降低，ROS、LPO、GSH 耗竭、MMP 崩溃和线粒体肿胀显著增加。我们观察到，50 和 100 μM SA 共处理 1 h 可有效改善线粒体功能障碍、ROS 积累、LPO、GSH 耗竭、线粒体膜电位去极化和线粒体肿胀引起的曲马多损伤。这些数据表明，线粒体损伤和氧化应激是曲马多诱导的神经毒性发病机制中的机制。此外，结果表明 SA 拮抗曲马多诱导的线粒体毒性，并提示 SA 可能是曲马多诱导的神经毒性并发症的预防/治疗剂。
