The effect of the radioprotector WR-2721 and WR-1065 on mitochondrial lipid peroxidation
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Updated: Aug 2, 2026

Fluorescence-Based Quantification of Mitochondrial Membrane Potential and Superoxide Levels Using Live Imaging in HeLa Cells
Published on: May 12, 2023
L Tretter1, E Rónai, G Szabados
1Second Institute of Biochemistry, Semmelweis University Medical School, Budapest, Hungary.
Abstract:
The radioprotective agent WR-2721 is dephosphorylated to the free thiol form WR-1065 in vivo. The effects of WR-2721, WR-1065 and reduced glutathione on a mitochondrial lipid peroxidation system were compared. WR-2721 had no effect on mitochondrial lipid peroxidation in vitro, and could not prevent the inactivation of mitochondrial enzymes. Both WR-1065 and glutathione were effective inhibitors of mitochondrial lipid peroxidation induced by ADP/Fe/NADPH or by ADP/Fe/ascorbate. Both thiols correspondingly delayed the free radical-mediated inactivation of succinate dehydrogenase and isocitrate dehydrogenase. WR-1065 was able to reduce cumene hydroperoxide non-enzymatically, and proved to be weak substrate for glutathione peroxidase. The disulfide formed from WR-1065 could be reduced by glutathione without the participation of glutathione reductase. A redox cycle is proposed between WR-1065, glutathione and glutathione reductase to explain the inhibitory effect of WR-1065 on lipid peroxidation.
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