Mechanism of hydroxyl radical scavenging by rebamipide: identification of mono-hydroxylated rebamipide as a major reaction product.
Free Radic Res
; 38(5): 487-94, 2004 May.
Article
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| MEDLINE
| ID: mdl-15293556
ABSTRACT
Rebamipide, an antiulcer agent, is known as a potent hydroxyl radical (*OH) scavenger. In the present study, we further characterized the scavenging effect of rebamipide against *OH generated by ultraviolet (UV) irradiation of hydrogen peroxide (H2O2), and identified the reaction products to elucidate the mechanism of the reaction. Scavenging effect of rebamipide was accessed by ESR using DMPO as a *OH-trapping agent after UVB exposure (305 nm) to H2O2 for 1 min in the presence of rebamipide. The signal intensity of *OH adduct of DMPO (DMPO-OH) was markedly reduced by rebamipide in a concentration-dependent fashion as well as by dimethyl sulfoxide and glutathione as reference radical scavengers. Their second order rate constant values were 5.62 x 10(10), 8.16 x 10(9) and 1.65 x 10(10) M(-1) s(-1), respectively. As the rebamipide absorption spectrum disappeared during the reaction, a new spectrum grew due to generation of rather specific reaction product. The reaction product was characterized by LC-MS/MS and NMR measurements. Finally, a hydroxylated rebamipide at the 3-position of the 2(1H)-quinolinone nucleus was newly identified as the major product exclusively formed in the reaction between rebamipide and the *OH generated by UVB/H2O2. Specific formation of this product explained the molecular characteristics of rebamipide as a potential *OH scavenger.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Depuradores de Radicales Libres
/
Radical Hidroxilo
/
Quinolonas
/
Alanina
/
Peróxido de Hidrógeno
/
Antiulcerosos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
Free Radic Res
Asunto de la revista:
BIOQUIMICA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Japón