Previous studies have reported that
KIOM-79 shows a strong inhibitory effect on AGE formation and inhibited a proinflammatory state in a murine macrophage cell line. In the present study, we investigated the effect of
KIOM-79 on AGE accumulation and vascular
inflammation in the aorta of Zucker diabetic fatty (ZDF) rats, a commonly used model of
type 2 diabetes. Seven-week-old male ZDF rats were treated with
KIOM-79 (50 mg/kg) once a day orally for 13 weeks. We examined the dissected aortas for AGE accumulation, expression of the receptor for AGEs (RAGE), and the expression of proinflammatory factors, including
monocyte chemoattractant protein-1 (MCP-1),
vascular endothelial growth factor (
VEGF), and vascular adhesion molecule-1 (VCAM-1).
Nuclear factor-kappaB (NF-κB) and
inducible nitric oxide synthase (iNOS) were also measured by Southwestern histochemistry, electrophoretic mobility shift assay (EMSA), and immunohistochemistry, respectively.
KIOM-79 markedly reduced the accumulation of AGEs and the expression of RAGE in the aorta. We also found that
KIOM-79 attenuated the expression of inflammatory factors including NF-κB, MCP-1,
VEGF,
VCAM-1, and iNOS in the aortas of ZDF rats. These data suggest that
KIOM-79 may prevent or retard the development of
inflammation in
diabetic vascular disease.