The role of
reactive oxygen species in diabetes and its complications are well known. Two therapeutic agents commonly used in the treatment of diabetes are the sulfonylureas,
gliclazide and
glibenclamide. These drugs effectively reduce
blood sugar in non-
insulin dependent diabetes millitus by augmenting
insulin release.
Gliclazide is known to be a general
free radical scavenger as demonstrated by inhibition of
o-dianisidine photo-oxidation. In this study, the effects of
gliclazide and
glibenclamide on
free radicals were examined in vitro, using electron spin resonance (ESR) spectroscopy.
Superoxide radical (O2.-) generated from
hypoxanthine-xanthine oxidase system, or
hydroxyl radical (.
OH) generated by the Fenton reaction, were analyzed as spin adducts of
5,5-dimethyl-1-pyrroline-N-oxide (DMPO). NO was generated from 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7), and analyzed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (carboxy-PTI) produced from the reaction between
2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (
carboxy-PTIO) and NO.
Gliclazide scavenged O2.-, .
OH and NO in a dose-dependent manner whereas
glibenclamide was without effect. These findings suggest that
gliclazide is not only effective in reducing
blood sugar but also may be beneficial by inhibition of
lipid and protein denaturation, which leads to the development of
diabetic complications.