Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, PR China; Institute of Biophysics, Chinese Academy of Science, Beijing 100101, PR China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, PR China; Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, PR China.
Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, PR China; Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, PR China.
Free Radic Biol Med. 2024 Nov 1;224:117-129. doi: 10.1016/j.freeradbiomed.2024.08.022. Epub 2024 Aug 22.
MitoTEMPO (MT) and Visomitin (SKQ1) are regareded as mitochondria-targeted antioxidants, which inhibit production of mitochondrial reactive oxygen species (ROS). However, the differences in function between MT and SKQ1 remain unexplored. Herein, we investigated the differential potency of MT and SKQ1 in mitigating oxidative stress under different conditions. The results indicated that high levels of SKQ1 induced cell death. The appropriate concentrations of MT and SKQ1 can prevent or rescue cell damage triggered by hydrogen peroxide (HO) and menadione (MEN). MT and SKQ1 reduced ROS levels and reversed the down-regulation of antioxidant defence genes and enzymes. These effects can alleviate the damage to lipids, proteins, and deoxyribonucleic acid (DNA) caused by oxidative stress and restore adenosine 5' triphosphate (ATP) generation. Subsequently, we found that MT administration in ischemic reperfusion kidney injury in mice provided superior renal protection compared to SKQ1, as evidenced by reduced plasma levels of kidney injury markers, improved renal morphology, decreased apoptosis, restored mitochondrial function, and enhanced antioxidant capacity. Overall, our findings suggest that MT is safer and has greater potential than SKQ1 as a therapeutic agent to mitigate oxidative stress damage or oxidative renal injury.
MitoTEMPO (MT) 和 Visomitin (SKQ1) 被认为是线粒体靶向抗氧化剂，可抑制线粒体活性氧 (ROS) 的产生。然而，MT 和 SKQ1 的功能差异仍未得到探索。在此，我们研究了 MT 和 SKQ1 在不同条件下缓解氧化应激的效力差异。结果表明，高浓度的 SKQ1 诱导细胞死亡。适当浓度的 MT 和 SKQ1 可以预防或挽救过氧化氢 (HO) 和 menadione (MEN) 引发的细胞损伤。MT 和 SKQ1 降低了 ROS 水平，并逆转了抗氧化防御基因和酶的下调。这些作用可以减轻氧化应激对脂质、蛋白质和脱氧核糖核酸 (DNA) 的损伤，并恢复三磷酸腺苷 (ATP) 的产生。随后，我们发现与 SKQ1 相比，MT 给药可在小鼠缺血再灌注肾损伤中提供更好的肾脏保护作用，这表现在损伤标志物的血浆水平降低、改善的肾脏形态学、减少的细胞凋亡、恢复的线粒体功能和增强的抗氧化能力。总的来说，我们的研究结果表明，MT 比 SKQ1 更安全，更有潜力作为一种治疗剂来减轻氧化应激损伤或氧化肾损伤。
