The Effect of the Radioprotector WR-2721 and WR-1065 on Mitochondrial Lipid Peroxidation

L. Tretter Second Institute of Biochemistry, Semmelweis University Medical School, 1088 Puskin u. 9, H-1444, Budapest, Hungary

É. Rónai Frederic Joliot Curie National Research Institute for Radiobiology and Radiohygiene, 1088 Puskin u. 9, H-1121, Budapest, Hungary

Gy. Szabados Second Institute of Biochemistry, Semmelweis University Medical School, 1088 Puskin u. 9, H-1444, Budapest, Hungary

R. Hermann Frederic Joliot Curie National Research Institute for Radiobiology and Radiohygiene, 1088 Puskin u. 9, H-1121, Budapest, Hungary

A. Andó Second Institute of Biochemistry, Semmelweis University Medical School, 1088 Puskin u. 9, H-1444, Budapest, Hungary

I. Horváth Frederic Joliot Curie National Research Institute for Radiobiology and Radiohygiene, 1088 Puskin u. 9, H-1121, Budapest, Hungary

Summary

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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The Effect of the Radioprotector WR-2721 and WR-1065 on Mitochondrial Lipid Peroxidation

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The Effect of the Radioprotector WR-2721 and WR-1065 on Mitochondrial Lipid Peroxidation

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