Effect of gliclazide on cardiovascular risk factors involved in split-dose streptozotocin induced neonatal rat model: a chronic study

Appropriate experimental models are essential for understanding the underlying mechanisms of diabetes and its complications. Investigations have unsuccessfully tried to recreate in experimental animals the cardiovascular complications of diabetes seen in humans. Sulfonylureas have remained the mainstay of antidiabetic therapy for almost three decades. 1 However the benefits of sulfonylureas beyond glycemic control has to be investigated. Gliclazide a second-generation sulfonylurea was preferred in the present study due to its vascular benefits beyond glycemic control. 2 Gliclazide possesses free radical scavenging property due to presence of aminoazabicyclo-octane ring, which is absent in other sulfonylureas. 2 In T2DM patients elicited a greater suppression of hepatic glucose production. 3 Gliclazide, but not glibenclamide, glimepiride, glipizide or tolbutamide, inhibited low density lipoprotein oxidation and enhanced total plasma antioxidant capacity. Thus, gliclazide possesses antioxidant properties that produce measurable clinical effects at therapeutic doses. 4 Gliclazide reduces DNA damage and improves DNA repair in diabetic patients, thus it may protect against the oxidative stressrelated chronic diabetes complications, including cancer, by decreasing the level of DNA damage induced by reactive oxygen species. 5 Gliclazide reduces oxidative stress 6 in enhanced nitric oxide (NO)-mediated vasodilatation. Also decrease in blood pressure was shown after gliclazide treatment which was mediated through NOmediated vasodilatation. 7 Improving the oxidative status of patients by using gliclazide for its hemovascular properties independent of its hypoglycemic action has led to improvements in oxidative stress, ABSTRACT