Gliclazide decreases cell-mediated low-density lipoprotein (LDL) oxidation and reduces monocyte adhesion to endothelial cells induced by oxidatively modified LDL.
Low-density lipoprotein (LDL) oxidation has been suggested to play a key role in the pathogenesis of atherosclerosis, a major complication of diabetes mellitus. Gliclazide, a second-generation sulfonylurea, is widely used in the treatment of type II diabetes mellitus. Recently, a free-radical-scavenging activity of gliclazide has been reported. In the present study, we examined the effects of gliclazide on cell-mediated LDL oxidation and monocyte adhesion to endothelial cells induced by oxidatively modified LDL. Incubation of human monocytes and bovine aortic endothelial cells (BAE cells) with increasing concentrations of gliclazide (0 to 10 micrograms/mL) and native LDL (100 micrograms/mL) resulted in a dose-dependent diminution of cell-mediated LDL oxidation as assayed by measurement of thiobarbituric acid (TBA)-reactive substances (TBARS). In addition, exposure of BAE cells to gliclazide (0 to 10 micrograms/mL) and native LDL (100 micrograms/mL) induced a dose-dependent diminution of the oxidized LDL-induced monocyte adhesion to BAE cells as measured by the myeloperoxidase (MPO) assay. The effects of glyburide, another second-generation sulfonylurea, were also tested on cell-mediated oxidation of LDL and LDL-induced monocyte adhesion to the endothelium. No significant effect of this drug was observed on these two processes. These results therefore demonstrate that gliclazide is effective in vitro in reducing both cell-mediated LDL oxidation and monocyte adhesion to the endothelium. These findings suggest a potential beneficial effect of gliclazide in the prevention of atherosclerosis in diabetic patients.
Desfaits
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Metabolic Unit, Notre-Dame Hospital Research Center, Montreal, Canada.
Serri
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Renier
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D000818:Animals; D001011:Aorta; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019327:Copper Sulfate / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005907:Gliclazide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances
D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D005907:Gliclazide; D019327:Copper Sulfate; D005905:Glyburide