1. Academic Validation
  2. A comparative study of the efficiency of mitochondria-targeted antioxidants MitoTEMPO and SKQ1 under oxidative stress

A comparative study of the efficiency of mitochondria-targeted antioxidants MitoTEMPO and SKQ1 under oxidative stress

  • Free Radic Biol Med. 2024 Aug 22:224:117-129. doi: 10.1016/j.freeradbiomed.2024.08.022.
Bilin Liu 1 Lei Chen 2 Meng Gao 2 Mengting Dai 3 Yejing Zheng 2 Linke Qu 3 Junming Zhang 3 Guohua Gong 4
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, PR China.
  • 4 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, Tongji University, Shanghai, 200120, PR China. Electronic address: guohgong@wmu.edu.cn.
Abstract

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 (H2O2) 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.

Keywords

Comparative; Ischemia‒reperfusion; MitoTEMPO; Mitochondria-targeted antioxidant; Oxidative stress; SKQ1.

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