Normalization of Plasma Lipid Peroxides, Monocyte Adhesion, and Tumor Necrosis Factor-α Production in NIDDM Patients After Gliclazide Treatment

Desfaits, Anne-Cécile; Serri, Omar; Renier, Geneviève

doi:10.2337/diacare.21.4.487

Cited by 119 publications

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“…To date, only in vitro or ex vivo studies have been done that showed the inhibitory effects of gliclazide, a sulphonylurea hypoglycaemic drug, on enhanced adhesion of leukocytes to endothelial cells in high glucose conditions [16,17,18]. In this study, we clearly demonstrated the inhibition of leukostasis in the diabetic retina in vivo by gliclazide, but not by another sulphonylurea drug, glibenclamide, supporting these previous in vitro and ex vivo studies [16,17,18] and explaining the observation in the previous clinical studies [21,22] in which gliclazide actually showed a preventive effect on progression of diabetic retinopathy compared with other sulphonylurea drugs in diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

“…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]. This radical-scavenging activity could be one of the mechanism of the inhibition of leukostasis observed in this study, because leukocytes in diabetic animals have been reported to be more activated [1,4] and produce more oxygen-derived free radicals [5,6], which induce vascular endothelial dysfunction [7,8,9].…”

Section: Discussionmentioning

confidence: 99%

“…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]. In an in vitro study using gliclazide, lower adhesion of neutrophils to cultured endothelial cells was also shown [18].…”

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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%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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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“…In patients with type-2 diabetes mellitus, glibenclamide administration inhibits increased monocyte adhesion to endothelial cells, thus decreasing TNF-α production by these cells 30 . In mice, glibenclamide did not have an effect on the production of TNF-α and had very little effect on the activity of this cytokine, according to Fukuzawa et al 31 .…”

Section: Serum Concentrations and Renal Expressions Of Il-1 And Tnf-amentioning

confidence: 99%

Serum concentrations and renal expressions of IL-1 and TNF-a early after hemorrhage in rats under the effect of glibenclamide

et al. 2016

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PURPOSE:To investigate changes in the serum concentration and renal expression of IL-1 and TNF-α cytokines in rats that received sevoflurane and glibenclamide prior to hemorrhage. METHODS:Two groups of sevoflurane-anesthetized Wistar rats (n=10): G1 (control) and G2 (glibenclamide, 1 µg/g i.v.); hemorrhage of 30% blood volume (10% every 10 min), with replacement using Ringer solution, 5 ml/kg/h. Serum concentrations of IL-1 and TNF-α were studied in the first hemorrhage (T1) and 50 min later (T2), renal expression, at T2. RESULTS:In serum, G1 TNF-α (pg/mL) was T1=178.6±33.5, T2=509.2±118.8 (p<0.05); IL-1 (pg/mL) was T1=148.8±31.3, T2=322.6±115.4 (p<0.05); in G2, TNF-α was T1=486.2±83.6, T2=261.8±79.5 (p<0.05); IL-1 was T1=347.0±72.0, T2= 327.3±90.9 (p>0.05). The expression of TNF-α and IL-1 in the glomerular and tubular cells was significantly higher in the G2 group. CONCLUSIONS:Hemorrhage and glibenclamide elevated TNF-α and IL-1 concentrations in serum and kidneys. High levels of TNF-α already present before the hemorrhage in the glibenclamide group may have attenuated the damages found in the kidneys after the ischemia event.Key words: Hemorrhage. Glyburide. Cytokines. Kidney. Rats. Serum concentrations and renal expressions of IL-1 and TNF-a early after hemorrhage in rats under the effect of glibenclamide

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Atherosclerosis: Risk Factors and Medical Management

DePalma¹,

Hayes²

2005

Vascular Surgery

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Normalization of Plasma Lipid Peroxides, Monocyte Adhesion, and Tumor Necrosis Factor-α Production in NIDDM Patients After Gliclazide Treatment

Cited by 119 publications

References 0 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

Serum concentrations and renal expressions of IL-1 and TNF-a early after hemorrhage in rats under the effect of glibenclamide

Atherosclerosis: Risk Factors and Medical Management

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