Cancer chemopreventive oltipraz generates superoxide anion radical.
The cancer chemopreventive actions of oltipraz, a member of a class of 1,2-dithiolethiones, have been primarily associated with the induction of phase 2 enzymes mediated by a 41bp enhancer element known as the anti-oxidant response element in the promoter regions of many phase 2 genes. It has been suggested that oxygen radical formation by oltipraz may be a critical mechanism by which it exerts chemoprevention. Therefore, in the present work, studies were performed to directly determine if oltipraz generates oxygen free radicals. Electron paramagnetic resonance (EPR) spin trapping demonstrated that oltipraz slowly reacts in the presence of oxygen to generate the superoxide anion radical. This formation of superoxide by oltipraz was concentration- and time-dependent. EPR oximetry studies showed that oxygen was also slowly consumed paralleling the process of superoxide formation. Thus, oltipraz induced superoxide formation occurs and could be involved in the mechanism by which it exerts chemoprotection.
Velayutham
Murugesan
M
Department of Internal Medicine, Center for Biomedical EPR Spectroscopy and Imaging, The Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Villamena
Frederick A
FA
Fishbein
James C
JC
Zweier
Jay L
JL
D000970:Antineoplastic Agents / Q000008:administration & dosage; D002460:Cell Line; D018890:Chemoprevention / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000138:chemical synthesis / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism*; D011719:Pyrazines / Q000008:administration & dosage* / Q000737:chemistry*; D013481:Superoxides / Q000138:chemical synthesis* / Q000378:metabolism*; D013871:Thiones; D013876:Thiophenes
D000970:Antineoplastic Agents; D005609:Free Radicals; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; D013481:Superoxides; C026209:oltipraz; D010100:Oxygen