In vitro and in vivo antioxidant properties of gliclazide

O'Brien, Richard C; Luo, Ming; Balazs, N.D.H.; Mercuri, J.

doi:10.1016/s1056-8727(00)00084-2

Cited by 122 publications

(86 citation statements)

References 26 publications

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“…Gliclazide could have certain non-metabolic effects specifically related to vascular function, which other sulphonylurea agents might not have [13,14,15,16,17,18,32,33,34]. For example, gliclazide was reported to have free-radical scavenging activity [13,14,15,16].…”

Section: Discussionmentioning

confidence: 99%

“…For example, gliclazide was reported to have free-radical scavenging activity [13,14,15,16]. It was shown that gliclazide reduced oxidized low-density lipoprotein (LDL)-induced monocyte adhesion to cultured endothelial cells as well as vascular cell-mediated LDL oxidation in vitro [16] and that gliclazide given to patients with Type II diabetes inhibits the increased adhesiveness of diabetic monocytes to cultured endothelial cells [17].…”

Section: Discussionmentioning

confidence: 99%

“…Gliclazide, a second generation sulphonylurea that has free radical scavenging activity [13,14,15,16], is widely used for the treatment of Type II (non-insulindependent) diabetes mellitus. It was shown that enhanced adhesion of diabetic patients' monocytes to cultured bovine aortic endothelial cells was normalized after treating the patients with gliclazide [17].…”

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confidence: 99%

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Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide

Kinoshita¹,

Kakehashi²,

Inoda

et al. 2002

Diabetologia

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Aims/hypothesis. Early stage leukocyte entrapment in the retinal microcirculation (retinal leukostasis) is considered to be one of the important pathogenetic events in diabetic retinopathy. Gliclazide, a sulphonylurea, was reported to reduce leukocyte adhesion to endothelial cells in hyperglycaemia in vitro, thus suggesting possible selective efficacy of this sulphonylurea in preventing leukostasis in diabetic patients. This study evaluated the effectiveness and selectivity of gliclazide treatment on retinal leukostasis of diabetic rats in vivo. Methods. Streptozotocin (STZ) (65 mg/kg)-induced diabetic rats were divided into three groups (n = 8 each): an untreated diabetic group, a gliclazide-treated diabetic group, and a glibenclamide-treated diabetic group. Gliclazide or glibenclamide was administered orally during a 3-week period. Non-diabetic rats were used as a control (n = 8). Retinal leukostasis was quantitatively evaluated in vivo by acridine orange leukocyte fluorography using a scanning laser ophthalmoscope.Results. The number of leukocytes trapped in the area around the optic disc in the untreated diabetic group (36.9 ± 5.1 cells) increased significantly compared with the non-diabetic control group (21.9 ± 2.9 cells; p = 0.0007). The number of leukocytes trapped in the gliclazide-treated diabetic group (23.5 ± 4.0 cells) decreased significantly compared with untreated diabetic group (p = 0.0008). In contrast, no reduction of retinal leukostasis was found in the glibenclamide-treated diabetic group (37.8 ± 5.8 cells; p = 0.7923). Conclusion/interpretation. This suggests that gliclazide could directly improve abnormalities in the retinal microcirculation independent of blood glucose control and possibly have selective therapeutic benefits in preventing early, critical events in diabetic retinopathy compared with other sulphonylurea drugs. [Diabetologia (2002) 45:735-739] Keywords Gliclazide, sulphonylurea, diabetic retinopathy, retinal leukostasis, acridine orange leukocyte fluorography, scanning laser ophthalmoscope. Diabetic retinopathy is a leading cause of adult vision loss and blindness and early-stage, preventive strategies are important research areas. Leukocyte adhesion to the diabetic retinal vasculature is presumed to be the critical early event in the pathogenesis of diabetic retinopathy [1,2,3], resulting in a breakdown in the blood-retinal barrier and in capillary nonperfusion [1,4,5,6,7,8,9,10,11,12]. In a rat model of diabetic retinopathy, investigators demonstrated retinal capillary occlusion by neutrophils and monocytes in histologic sections and found that areas of endothelial cell damage, capillary loss, and leukocyte extravasation existed adjacent to the static leukocytes [1]. In another post mortem study of human subjects, increased numbers of neutrophils were observed in the choroid and retina of patients with diabetes [2].

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide

Kinoshita¹,

Kakehashi²,

Inoda

et al. 2002

Diabetologia

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“…This hypothesis can be supported by many observations which suggest that the activity of oral betacytotropic drugs is pleiotropic and not limited solely to the stimulation of beta cells. They produce many other therapeutically positive effects, among them a decrease in insulin resistance (Almer 1984;Fava et al 2002;Gram et al 1988;Itoh et al 2003;Jennings et al 1992;O'Brien et al 2000). This may also involve the activity of the CGT system.…”

Section: Introductionmentioning

confidence: 99%

Cellular glucose transport and glucotransporter 4 expression as a therapeutic target: clinical and experimental studies

Czech

Piątkiewicz

Tatoń

2009

Arch. Immunol. Ther. Exp.

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Introduction: The normalization of cellular glucose assimilation is the basic aim of metabolic therapy in type 2 diabetes mellitus (T2DM). It requires parallel changes in the process of cellular glucose transport (CGT). Therefore the level of CGT could be regarded as a therapeutic target for oral hypoglycemic drugs in T2DM. To explore this hypothesis, CGT levels before and after sulfonylurea therapy were investigated. Peripheral blood lymphocytes were used as a cell model for testing CGT. Materials and Methods: CGT was assessed by experimental in vitro tests allowing timed comparative observation of the transport process during the incubation of lymphocytes with 2-[ 3 H(G)] glucose under basal conditions and after the addition of sulfonylurea or sulfonylurea plus insulin. The incubation tests were performed at baseline in 28 persons with newly diagnosed, therapy-naive T2DM and in 20 control subjects. In the diabetic patients the tests for CGT were repeated after 3 months of sulfonylurea therapy. The level of glucotransporter 4 (GLUT4) expression was also assessed by flow cytometry before and after the therapy. Results: Before treatment, CGT was significantly lower in the subjects with T2DM. The cells responded to the addition of sulfonylurea by a moderate increase in CGT. This response was augmented by the addition of insulin to sulfonylurea in the culture medium. Conclusions: The three-month therapy with sulfonylurea resulted in a significant increase in CGT in all types of culture tests. This sulfonylurea-related improvement in CGT was associated with a near normalization of GLUT4 expression in the cells.

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“…Some results have demonstrated that repaglinide might result in a positive action on the antioxidative defense [9,10]. Several studies have also shown that sulphonylureas have similar properties [11][12][13]. However, these effects in type 2 diabetes mellitus are difficult to interpret, as any action could not be separated from effects mediated via increased insulin secretion.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress in the testis of hyperglycemic rabbits treated with repaglinide

2007

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Abstract:In the present study, the induction of oxidative stress was examined in the testis of alloxaninduced diabetic rabbits. In addition, the protective effect of repaglinide, an oral anti-diabetic, at a dose of 1 mg daily was studied after four and eight weeks of the treatment. For these purposes, the levels of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH), ascorbic acid (AA), lipid peroxidation products (LPO) and protein carbonyl groups (PCG) were quantified. Hyperglycemia resulted in significant increases in the antioxidative enzymes, Cu, Zn-SOD, CAT, GSH-Px, and GSSG-R after four and eight weeks, respectively. There was also an increase in GSH level, and a decrease in the level of AA. These effects were accompanied by an elevation in testicular LPO levels and PCG levels. Repaglinide was found to normalize the activity of GSSG-R and levels of GSH and AA, and blunted the increased lipid peroxidation, however no decrease in PCG levels were observed. In conclusion, some oxidative changes provoked in the testis of rabbits by hyperglycemia, were found to be reduced with repaglinide treatment at therapeutic dose.

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In vitro and in vivo antioxidant properties of gliclazide

Cited by 122 publications

References 26 publications

Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide

Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide

Cellular glucose transport and glucotransporter 4 expression as a therapeutic target: clinical and experimental studies

Oxidative stress in the testis of hyperglycemic rabbits treated with repaglinide

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