Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits

Abstract

Background:Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs, useful for control of diabetes mellitus type two and it may exert anti inflammatory activity, by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway. Repaglinide is a new hypoglycemic agent, and a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has favorable effects on the parameters of antioxidative balance.Objectives:The objective of the present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with the inflammatory and oxidative pathways.Materials and Methods:Twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits were fed with 1% cholesterol enriched diet. Group III rabbits were fed with 1% cholesterol enriched diet together with Glimepiride (0.1 mg/kg once daily before morning feed). Group IV rabbits were fed with 1% cholesterol enriched diet together with Repaglinide (0.3 mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), high sensitive C - reactive protein (hsCRP), Interleukin – 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α) levels. At the end of 10 weeks, the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness.Results:Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group (P < 0.05). Also, they significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P < 0.05), and they helped to restore the aortic GSH levels (P < 0.05).Conclusions:Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbits by interfering with the inflammatory and oxidative pathways without affecting lipid parameters.

Effect of glimepiride on the aorta of adult albino rats after induction of diabetes mellitus

“…These findings coincided with those of Hadi et al [21]. These findings coincided with those of Hadi et al [21].…”

“…This was found previously by Hadi et al [21] who stated that atherosclerosis is an inflammatory disease of the blood vessel wall, characterized during early stages by endothelial dysfunction and activation of monocytes/macrophages. A collection of foam cells was seen in the subendothelial region and in the media during light microscopic examination.…”

Differences between Mitiglinide/Voglibose Fixed-dose Combination and Glimepiride in Modifying Low-density Lipoprotein Heterogeneity in Japanese Type-2 Diabetic Patients: A Pilot Study

“…In addition, it is reasonable that when serum LDL-C levels are reduced, levels of sd-LDL, which constitutes LDL, are also reduced. It has also been reported that glimepiride has antiatherosclerotic effects such as an LDL oxidation inhibitory effect [16][17][18]. However, mitiglinide/voglibose fixed-dose combination did not change serum LDL-C levels significantly, but reduced the ratio of sd-LDL to LDL, i. e., sd-LDL proportion, and increased the mean particle size of all LDL particles, which is represented by LDL-C/apoB, indicating that mitiglinide/voglibose fixed-dose combination has an effect of inhibiting LDL-induced arteriosclerosis, an effect different from that of glimepiride [13,19].…”

High cholesterol diet effects on ischemia–reperfusion injury of the heart

“…In clinical practice, exogenous cholesterol is interesting since modifying eating habits can help lower cholesterol leveles. Some research was carried out on laboratory animals to evaluate hypercholesterolemia as follows: a) on genetically modified animals (endogenous) (Song G. et al 2011, Dworschak M et al 2005; b) on high-cholesterol-fed animals (exogenous) (Bulgarelli A et al 2011;Hadi NR et al 2012); c) combining both (endogenous and exogenous) (Ishibashi S et al 2011, Scalia R et al 2001…”