The effect of the radioprotector WR-2721 and WR-1065 on mitochondrial lipid peroxidation.
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.
Tretter
L
L
Second Institute of Biochemistry, Semmelweis University Medical School, Budapest, Hungary.
Rónai
E
E
Szabados
G
G
Hermann
R
R
Andó
A
A
Horváth
I
I
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D005980:Glutathione Reductase / Q000378:metabolism; D066298:In Vitro Techniques; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008624:Mercaptoethylamines / Q000494:pharmacology*; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013385:Succinate Dehydrogenase / Q000378:metabolism
D001555:Benzene Derivatives; D005609:Free Radicals; D008624:Mercaptoethylamines; D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D007521:Isocitrate Dehydrogenase; D013385:Succinate Dehydrogenase; D005980:Glutathione Reductase; D005978:Glutathione; D004999:Amifostine; C007164:cumene hydroperoxide