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.

Oral hypoglycaemic agent failure.

Type 2 diabetic patients initially respond satisfactorily to diet, exercise and oral hypoglycaemic agents (OHA), but a fraction of them acquires resistance to drugs, right from the beginning (primary OHA failure) or in due course of time (secondary OHA failure) and becomes insulin requiring ultimately. Poor diet compliance and deterioration of beta-cell function are major causes of OHA failure and annual incidence is 3 to 30%. Keeping in mind the benefit of organ salvage in diabetes, failure with OHA treatment should be detected earliest and necessary measures adopted as early as possible. Recognition, appraisal and assessment of total problem can help a diabetic to enjoy a normal life.

Glibenclamide vs gliclazide in reducing oxidative stress in patients of noninsulin dependent diabetes mellitus--a double blind randomized study.

OBJECTIVE: Parameters of oxidative stress were quantitated in 50 patients with type 2 diabetes mellitus in uncontrolled state and after control using oral glibenclamide or gliclazide. The estimates were further compared between the two groups irrespective of drug used to evaluate the difference, if any. METHODS: The study was a double blind, uncontrolled, noncrossover and randomized trial. Fifty patients of uncontrolled type 2 diabetes were divided in to two groups. Group I (25 patients) received capsule A (glibenclamide) while Group II (25 patients) received capsule B (gliclazide). The parameters studied were Superoxide dismutase (SOD), malonyl-dialdehyde (MDA) and reduced glutathione (GSH). They were done at (a) uncontrolled stage (FBS--165 +/- 16.7 mg/dl, PP--240 +/- 30.1 mg/dl and HbA1--10.5 +/- 0.9% in group I and FBS--150 +/- 15.8 mg/dl, PP--246 +/- 29.1 mg/dl HbA1 10.6 +/- 0.8% in group II) and during controlled stage at 12 weeks (FBS--120 +/- 18.5 mg/dl, PP--180 +/- 19.1 mg/dl and HbA1--8.4 +/- 0.29% in group I and FBS--118 +/- 17.6 mg/dl, PP--176 +/- 20.1 mg/dl and HbA1--8.5 +/- 0.39% in group II patients). RESULTS: The significantly raised levels of MDA and SOD, and decreased levels of reduced glutathione (GSH) during uncontrolled stage of diabetes indicated free radical stress induced lipid peroxidation. The significant fall of MDA and SOD and increased levels of GSH in blood in both groups after control revealed beneficial effects of glycemic control on oxidative stress. The levels were not normalized and stayed higher than those in controls. On intergroup comparison; the control of diabetes with gliclazide (group II) showed improvement in oxidative stress (MDA, GSH) better (p < 0.001) than glibenclamide (group I). CONCLUSION: Oxidative stress in uncontrolled diabetes is decreased with glycemic control. The control of diabetes with gliclazide reduced oxidative stress more than glibenclamide, indicating higher antioxidant properties of gliclazide. Normalization of oxidative stress was not achieved. Further studies are required to see long-term effect of drug therapy in combating oxidative stress after achieving acceptable control of diabetes.

Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure

To determine the effects of combined therapy of gliclazide and bedtime insulin on glycemic control and C-peptide secretion, we studied 25 patients with type 2 diabetes and sulfonylurea secondary failure, aged 56.8 + or - 8.3 years, with a duration of diabetes of 10.6 + or - 6.6 years, fasting plasma glucose of 277.3 + or - 64.6 mg/dl and a body mass index of 27.4 + or - 4.8 kg/m². Patients were submitted to three therapeutic regimens lasting 2 months each: 320 mg gliclazide (phase 1), 320 mg gliclazide and bedtime NPH insulin (phase 2), and insulin (phase 3). At the end of each period, glycemic and C-peptide curves in response to a mixed meal were determined. During combined therapy, there was a decrease in all glycemic curve values (P<0.01). Twelve patients (48 percent) reached fasting plasma glucose <140 mg/dl with a significant weight gain of 64.8 kg (43.1-98.8) vs 66.7 kg (42.8-101.4) (P<0.05), with no increase in C-peptide secretion or decrease in HbA1. C-Peptide glucose score (C-peptide/glucose x 100) increased from 0.9 (0.2-2.1) to 1.3 (0.2-4.7) during combined therapy (P<0.01). Despite a 50 percent increase in insulin doses in phase 3 (12 U (9-30) vs 18 U (11-60); P<0.01) only 3 patients who responded to combined therapy maintained fasting plasma glucose <140 mg/dl (P<0.02). A tendency to a higher absolute increase in C-peptide (0.99 (0.15-2.5) vs 0.6 (0-2.15); P = 0.08) and C-peptide incremental area (2.47 (0.22-6.2) vs 1.2 (0-3.35); P = 0.07) was observed among responders. We conclude that combined therapy resulted in a better glucose response to a mixed meal than insulin alone and should be tried in type 2 diabetic patients before starting insulin monotherapy, despite difficulties in predicting the response

Evaluación de la gliclazida como hipoglicemiante oral / Evaluation of glycazide as oral hypoglycemiant

Se estudiaron en total noventa y seis pacientes diabéticos tipo II, en su mayoría recién diagnosticados. Fueron suguidos durante un lapso de tres meses de tratamiento con gliclazida, después de un período de dieta de un mes sin obtener resultados satisfactorios en el control de la diabetes. La gliclazida se administró en la dosis de 80 a 240 mg. La glicemia en ayunas fue determinada al inicio del período de dieta, al comenzar el tratamiento con gliclazida, a las dos semanas (para reajustar la dosis) y luego al mes, dos y tres meses se seguir esta medicación. La hemoglobina glicosilada total se midío al inicio y al final del tratamiento. En ambos parámetros se encuentra un descenso significativo de los valores, lo cual muestra un resultado satisfactorio sobre el control de la diabetes. En las curvas de glicemia e insulinemia no se encuentran diferencias significativas antes y despues del período de dieta. En cambio, hay una mejoría importante de la tolerancia a la glucosa a los tres meses del tratamiento con la gliclazida. Hay también a los tres meses un incremento de la secreción de isulina estimulada por glucosa a los 15, 30 y 90 minutos, con valores prácticamente iguales en las tres etapas del estudio (ates de la dieta, antes de iniciar la gliclazida y a los tres meses de su administración) a las dos horas de la sobrecarga con glucosa. En lo que respecta a los lípidos plasmáticos, hay pocas variaciones con el tratamiento en los niveles de colestrol, colesterol-HDL y triglicéridos. Hubo buena tolerancia del medicamento

Estudio abierto de la gliclazida en diabeticos tipo II (NID) / Open study of glicazicle in diabetic type II (NID)

Se estudiaron treinta y dos (32) pacientes diabéticos no insulino dependientes (NID) por un lapso de 6 meses, sometidos a régimen dietético y gliclazida en dosis de 80 a 240 mg/día. Se hizo determinación de glicemia en ayunas, de lípidos plasmáticos y de hemoglobina glicosilada total (HbAl) al inicio, al cabo de un mes, de tres y de seis meses de tratamiento. Los resultados muestran un descenso significativo de la glicemia en ayunas desde el primer mes de tratamiento y la hemoglobina bajó a niveles cercanos a lo normal, a los tres y seis meses de observación

Estudo da gliclazide nos pacientes diabéticos näo insulino-dependentes / Gliclazide in non-insulin dependent diabetics

Trinta e um diabéticos declarados näo insulino-dependentes e näo equilibrados por regime alimentar exclusivo receberam, em média, durante três meses, 180mg diários de gliclazide, associada a um regime hipocalórico da ordem de 1.600 a 1.800 calorias por dia. Todos os parâmetros inicialmente alterados (glicemias em jejum e pós-prandial, hipertrigliceridemia, hipercolesterolemia, hemoglobina glicosilada) foram corrigidos de maneira importante e estatisticamente significativa. Näo houve interrupçäo de tratamento no decorrer do estudo, sendo muito satisfatória a aceitabilidade clínica e biológica

Tratamento do diabetes com a gliclazide / Treatment of diabetis with gliclazide

Os autores estudaram a eficácia hipoglicemiante da gliclazide sobre dois grupos de pacientes diabéticos näo insulino-dependentes: diabéticos que näo tinham recebido nenhum tratamento hipoglicemiante preliminar e doentes submetidos anteriormente a uma terapêutica hipoglicemiante oral. Observaram-se bons efeitos, tanto sobre os níveis de glicemia quanto nos valores dos triglicérides plasmáticos. Näo foi observado qualquer efeito colateral