In vitro and in vivo antioxidant properties of gliclazide

Diabetes is a state of increased oxidant stress and there is evidence that oxidation may play a role in the genesis of complications. Gliclazide, a sulfonylurea hypoglycemic drug, has been shown to possess free radical scavenging properties. This study examined the effects of in vitro supplementation with gliclazide and other sulfonylureas as on low-density lipoprotein (LDL) oxidation and the total plasma antioxidant capacity (TPAC). In a separate study, the effects of 10 months of oral gliclazide therapy on oxidative parameters were assessed in 44 type 2 diabetic patients. Gliclazide, but not glibenclamide, glimepiride, glipizide or tolbutamide, inhibited LDL oxidation and enhanced TPAC. With the addition of 1 mu M gliclazide, oxidation lag time increased from 53.6 +/- 2.6 to 113.6 +/- 5.1 min (p < 0.001), and TPAC increased from 1.09 +/- 0.11 to 1.23 +/- 0.11 mM (p < 0.01). Administration of either modified release or standard gliclazide to type 2 diabetic patients resulted in a fall in 8-isoprostanes, a marker of lipid oxidation, and an increase in the antioxidant parameters TPAC, SOD and thiols. These studies show that gliclazide possesses antioxidant properties that produce measurable clinical effects at therapeutic doses. (C) 2000 Elsevier Science Inc. All rights reserved.