In spite of the cardiotoxic effect of selective cyclooxygenase-2 inhibitors, they are most widely used as anti-inflammatory and analgesic drugs. Today, valdecoxib and rofecoxib have been withdrawn in the market but celecoxib remains. In this study, we focused on an analysis of celecoxib toxic effects on isolated mitochondria. Isolated rat heart mitochondria were obtained using differential centrifugation. Using flow cytometry and biochemical assays, we searched succinate dehydrogenases, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) formation, mitochondrial swelling, ATP/ADP ratio, lipid peroxidation, and mitochondrial complexes activity in rat heart isolated mitochondria. Herein, our results indicated a significant decrease in the activity of complex IV after exposure with celecoxib (16 µg/ml). This decrease in the activity of complex IV is paralleled by the MMP collapse, ROS formation, mitochondrial swelling, depletion of ATP, and lipid peroxidation. For the first time, this introductory study has shown a significant decrease in the activity of complex IV and mitochondrial dysfunction after exposure with celecoxib in rat heart isolated mitochondria.

中文翻译：

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塞来昔布在离体大鼠心脏线粒体中降低线粒体复合物 IV 活性并诱导氧化应激：对其心脏毒性副作用的分析

尽管选择性环氧合酶2抑制剂具有心脏毒性作用，但它们最广泛地用作抗炎和镇痛药物。如今，伐地昔布和罗非昔布已经退出市场，但塞来昔布仍然存在。在这项研究中，我们重点分析了塞来昔布对离体线粒体的毒性作用。使用差速离心获得分离的大鼠心脏线粒体。使用流式细胞术和生化分析，我们在大鼠心脏分离的线粒体中搜索了琥珀酸脱氢酶、线粒体膜电位 (MMP)、活性氧 (ROS) 形成、线粒体肿胀、ATP/ADP 比率、脂质过氧化和线粒体复合物活性。在此，我们的结果表明在接触塞来昔布（16 µg/ml）后复合物 IV 的活性显着降低。这种复合物 IV 活性的降低与 MMP 崩溃、ROS 形成、线粒体肿胀、ATP 消耗和脂质过氧化平行。这项介绍性研究首次表明，在大鼠心脏分离的线粒体中暴露于塞来昔布后，复合体 IV 的活性和线粒体功能障碍显着降低。