Gliclazide reduced oxidative stress, inflammation, and bone loss in an experimental periodontal disease model

Abstract Objective The aim of this study was to evaluate the effects of gliclazide on oxidative stress, inflammation, and bone loss in an experimental periodontal disease model. Material and Methods Male albino Wistar rats were divided into no ligature, ligature, and ligature with 1, 5, and 10 mg/kg gliclazide groups. Maxillae were fixed and scanned using micro-computed tomography to quantify linear and bone volume/tissue volume (BV/TV) and volumetric bone loss. Histopathological, immunohistochemical and immunofluorescence analyses were conducted to examine matrix metalloproteinase-2 (MMP-2), cyclooxygenase 2 (COX-2), cathepsin K, members of the receptor activator of the nuclear factor kappa-Β ligand (RANKL), receptor activator of nuclear factor kappa-Β (RANK), osteoprotegerin (OPG) pathway, macrophage migration inhibitory factor (MIF), superoxide dismutase-1 (SOD-1), glutathione peroxidase-1 (GPx-1), NFKB p 50 (Cytoplasm), NFKB p50 NLS (nuclear localization signal), PI3 kinase and AKT staining. Myeloperoxidase activity, malondialdehyde and glutathione levels, while interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by spectroscopic ultraviolet-visible analysis. A quantitative reverse transcription polymerase chain reaction was used to quantify the gene expression of the nuclear factor kappa B p50 subunit (NF-κB p50), phosphoinositide 3-kinase (PI3k), protein kinase B (AKT), and F4/80. Results Micro-computed tomography showed that the 1 mg/kg gliclazide treatment reduced linear bone loss compared to the ligature, 5 mg/kg gliclazide, and 10 mg/kg gliclazide treatments. All concentrations of gliclazide increased bone volume/tissue volume (BV/TV) compared to the ligature group. Treatment with 1 mg/kg gliclazide reduced myeloperoxidase activity, malondialdehyde, IL-1β, and TNF-α levels (p≤0.05), and resulted in weak staining for COX-2, cathepsin k, MMP-2, RANK, RANKL, SOD-1, GPx-1,MIF and PI3k. In addition, down-regulation of NF-κB p50, PI3k, AKT, and F4/80 were observed, and OPG staining was strong after the 1 mg/kg gliclazide treatment. Conclusions This treatment decreased neutrophil and macrophage migration, decreased the inflammatory response, and decreased bone loss in rats with ligature-induced periodontitis.

Effects of metformin plus gliclazide versus metformin plus glimepiride on cardiovascular risk factors in patients with type 2 diabetes mellitus

High blood glucose level, lipid profile disturbances and plasma homocysteine [Hey] are important risk factors for cardiovascular diseases in patients with type 2 diabetes. This study was conducted to evaluate and compare effects of glimepiride/metformin combination versus gliclazide/metformin combination on cardiovascular risk factors in type-2 diabetes mellitus [T2DM] patients. One hundred and eighty T2DM patients were randomly allocated for treatment with placebo [control], metformin [500mg twice daily], glimepiride [3mg once daily], gliclazide [80mg once daily], metformin plus glimepiride or metformin plus gliclazide for 3 months. We evaluated plasma levels of glucose [PG], glycated hemoglobin [HbAlC], Hey, vitamin B12, folic acid and lipid profile before treatment and 3 months post treatment. Compared to metformin treated patients, glimepiride plus metformin induced significant reductions in: fasting plasma glucose, postprandial PG level, HbAlC % and Hey level. Conversely, plasma folic acid and vitamin B12 were significantly increased. The levels of total cholesterol and triglyceride were significantly decreased; low-density lipoprotein was markedly decreased, whereas high-density lipoprotein was significantly increased and hence risk ratio was significantly decreased. Similar results but with lower values were obtained using combination of metformin plus gliclazide on glycemic control only. Combination of glimepiride with metformin was superior to gliclazide plus metformin in alleviating the cardiovascular risk factors in type 2 diabetes mellitus patients

Study of the effect of Panax ginseng versus Gliclazide on hyperglycaemia induced by Dexamethasone in experimental animals

To study the effect of panax ginseng versus gliclazide on hyperglycaemia induced by dexamethasone in experimental animals. The current study was conducted in the Department of Pharmacology, University of Science and Technology, Sana'a, Yemen. Twenty-four rabbits were divided to 4 groups. Three of them were administered oral doses of dexamethasone [10 mg/kg] for 14 days, one group was kept as a control. Ginseng at dose [200 mg/kg] and gliclazide [80 mg/kg] were administered to rabbits with dexamethasone-induced hyperglycaemia. The effects of ginseng and gliclazide on fasting blood sugar [FBS] and body weight after continuous administration of dexamethasone [10 mg/kg] were measured. Oral administration of ginseng [200mg/kg] for 2 weeks produced significant [p < 0.05] reduction in FBS from 215.33 +/- 27.67 mg/dl in the dexamethasone group to 154.17 +/- 21.18mg/dl in the ginseng treated group. In addition, ginseng produced significant [p < 0.05] reduction in body weight. There was a significant difference between ginseng and gliclazide in reduction of FBS and body weight. From these results, it is suggested that ginseng could be used in obese diabetic patients or those suffering from insulin resistance as it reduces body weight

Effect of aqueous extract of Cyamopsis tetragonoloba Linn. beans on blood glucose level in normal and alloxan-induced diabetic rats.

Effect of feeding orally the aqueous extract of beans of Cyamopsis tetragonoloba was investigated on fasting blood glucose levels in glucose loaded, normal and alloxan-induced diabetic rats and compared with gliclazide, a reference drug. The aqueous extract of beans at 250 mg/kg body wt significantly lowered blood glucose levels in alloxan-induced diabetic rats within 3 hr of administration. Continued administration of the extract at the same dose daily for 10 days produced statistically significant reduction in the blood glucose levels while marginal activity was seen in normal and glucose-loaded rats.

Effect of certain oral hypoglycemic drugs on central monoamines contents with relation to behavioral activities in adult diabetic male albino mice

The effect of glibenclamide, glipizide and gliclazide on brain norepinephrine, dopamine and serotonin contents in different brain regions of diabetic mice with correlation to behavioral activities were investigated. Alloxan-induced diabetes produced a significant decrease in norepinephrine contents in medulla, pons and cerebellum, with a decrease in dopamine contents in all tested brain regions, while serotonin contents was increased in cerebral cortex and thalamus hypothalamus. These effects were accompanied by reduction in behavioral activities of mice [sniffing, rearing, grooming, chewing, stillness, time of immobility, and pain threshold]. Sulphonylureas significantly increased brain norepinephrine and dopamine contents in different brain regions and antagonized the behavioral activities of diabetic mice. On the other h and, these drugs produced a significant decrease in serotonin contents, an action accompanied by an increase in time of immobility and pain threshold

Evaluación de la tolerancia y eficacia de la gliclazida a corto plazo en diabéticos no insulino-dependientes / Evaluation of the tolerance and efficacy of gliclazide to short time in non insulino-dependents diabetics

En un ensayo abierto con 40 diabéticos no insulinodependientes se evalúa la respuesta hormonal y terapéutica a una nueva sulfonilurea, la gliclazida administrada a corto plazo (12 semanas). Como parámetros se emplean las determinaciones de insulinemia y Péptido C en ayunas, post-prandial, así como luego de una sobrecarga de glucosa con valores a los 0,30,60,90,120 y 180 minutos, antes y al final de las 12 semanas. Como criterio de eficacia terapéutica, se tomó la Hemoglobina Glicosilada. La tolerancia a la gliclazidea es muy satisfactoria, al juzgar por sólo 2 casos, de los 40, que presentaron mínimos efectos secundarios. Por lo expuesto consideramos a la gliclazida como una medicación de actividad betacitotrótica excelente en administración a corto plazo y dotada de muy buena tolerancia, lo cual, a nuestro criterio, la convierte en una sulfonilurea muy recomendable para el tratamiento de los diabéticos no insulinodependientes