5,5-dimethyl-1-pyrroline-N-oxide alone enhances the spontaneous superoxide generation by primaquine.
Primaquine (PQ), a well-known antimalarial drug, has been reported to generate superoxide (O2-) in the presence of reducing agents such as NADPH. In the present study, chemiluminescence was detected by adding only PQ to aqueous 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo-[1,2-alpha] pyrazin-3-one (MCLA), which is a specific chemiluminescent probe for O2-, and was quenched by superoxide dismutase (SOD), indicating that PQ alone can generate O2- in aerobic conditions. Furthermore, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) enhanced the O2- generation by PQ. Superoxide spin adduct, DMPO-OOH, was also detected by ESR both in aqueous solutions and in dimethyl sulfoxide with DMPO. The level of O2- generation showed a linear correlation with the DMPO concentration, and SOD competitively inhibited the DMPO-OOH formation. The results suggested that in aerobic conditions PQ is autoxidized to 5-hydroxy-PQ, which generates O2-, and DMPO accelerates the autoxidation process by trapping O2-. DMPO or M4PO alone enhances the spontaneous O2- generation by PQ, therefore cautious evaluation is necessary in all studies using the ESR/spin trapping technique to elucidate the mechanism of PQ-related radical generation.
Prónai
L
L
Second Department of Physiology, Tokai University School of Medicine, Kanagawa-ken, Japan.
Ichimori
K
K
Saigusa
Y
Y
Nakazawa
H
H
D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D007093:Imidazoles; D008163:Luminescent Measurements; D011319:Primaquine; D011719:Pyrazines; D013053:Spectrophotometry; D013113:Spin Labels; D013481:Superoxides
D003497:Cyclic N-Oxides; D007093:Imidazoles; D011719:Pyrazines; D013113:Spin Labels; D013481:Superoxides; C063412:2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo(1,2-alpha)pyrazin-3-one; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D011319:Primaquine