Gliclazide decreases low-density lipoprotein oxidation and monocyte adhesion to the endothelium

Increasing evidence implicates oxidized low-density lipoprotein (LDL) and a dvanced glycation end products (AGE) in the atherogenesis associated with d iabetes mellitus, In the present study, we examined the in vitro effects of gliclazide on LDL oxidation and monocyte adhesion to endothelial cells ind uced by oxidized LDL and glycated albumin. To assess the clinical relevance of our in vitro findings, we also measured the effect on monocyte adhesion of gliclazide administration to type 2 diabetic patients. Incubation of hu man monocytes and endothelial cells with increasing concentrations of glicl azide (0 to 10 mu g/mL) and native LDL (100 mu g/mL) induced a dose-depende nt diminution of cell-mediated LDL oxidation, Pretreatment of endothelial c ells with gliclazide (0 to 10 mu g/mL) before addition of native LDL (100 m u g/mL) or glycated albumin (100 mu g/mL) resulted in a dose-dependent dimi nution of oxidized LDL- and glycated albumin-induced monocyte adhesion to e ndothelial cells, In type 2 diabetic patients, administration of gliclazide inhibits the increased adhesiveness of monocytes to levels similar to thos e observed in control subjects. These results indicate that gliclazide is a n antioxidant and suggest a beneficial effect of this drug in the preventio n of atherosclerosis associated with type 2 diabetes. Copyright (C) 2000 by W.B. Saunders Company.