Glibenclamide In Rats Research Articles

Synergistic Effect of Glibenclamide Combining With Vitexin on Type 2 Diabetes Mellitus Rats

Background & objectives: The combination of drugs with herbs is a prevalent treatment for metabolic and chronic diseases. This study combined glibenclamide with vitexin and performed in vivo and in vitro investigations, aiming to evaluate their synergistic effect on type 2 diabetes mellitus (T2DM). Materials and methods: T2DM rat models were established by injecting streptozotocin, and the sham group was injected with a normal saline solution as the control. A single dosage was orally performed with 10 mg/kg glibenclamide, while the co-administrated was conducted by the pre-treatment of 20 mg/kg vitexin for 7 d to avoid potential chemical interactions. The pharmacokinetics of glibenclamide was evaluated in both sham and T2DM rats. The blood glucose of T2DM rats was detected in the presence of different administration strategies. The metabolic stability of glibenclamide was assessed in rat liver microsomes. Results: Glibenclamide showed a significant hypoglycemic effect on T2DM rats, which was enhanced by the co-administration of vitexin. Vitexin significantly affected the pharmacokinetics of glibenclamide in both sham and T2DM rats, where the AUC0-t, Cmax, and t1/2 of glibenclamide significantly increased, and the clearance rate decreased. Moreover, vitexin increased the in vitro half-life and decreased intrinsic clearance of glibenclamide in rat liver microsomes. The previously reported inhibitory effect of vitexin on CYP2C9 activity was hypothesized as the mechanism underlying the interaction. Conclusion: Co-administration of glibenclamide and vitexin would increase the systemic exposure and metabolic stability of glibenclamide and exert a synergistic effect on T2DM.

Vitamin D supplementation could enhance the effectiveness of glibenclamide in treating type 2 diabetes by improving the function of pancreatic β-cells through the NF-κB pathway

PurposeThe high morbidity and mortality associated with type 2 diabetes mellitus (T2DM) pose a significant global health challenge, necessitating the development of more efficient anti-diabetic drugs with fewer side effects. This study investigated the intervention of vitamin D3 combined with glibenclamide in rats with T2DM to elucidate its effects on pancreatic β-cells through the NF-κB pathway. MethodsTwenty-four healthy male Sprague-Dawley (SD) rats were randomly assigned to four groups: the control group (CG), the model group (MG), the glibenclamide group (GG), and the glibenclamide + vitamin D3 group (GDG). After inducing the T2DM model using high-fat and high-sugar diet and intraperitoneal injection of streptozotocin, the rats in the GG group were administered glibenclamide orally (0.6 mg/kg/day), while those in the GDG group received both glibenclamide (0.6 mg/kg/day) and vitamin D3 (500 IU/kg/day) in corn oil for a duration of 8 weeks. Biochemical indices were measured, and histopathological changes in pancreatic tissue and islet β cells were observed using hematoxylin and eosin staining. The expression of pancreatic nuclear factor κB (NF-κB), islet β-cells, and inflammatory cytokines were assessed using the TUNEL method and PCR. ResultsAccording to the data from this current study, the GDG group showed significant positive differences in plasma biochemical indices, as well as in the expression of β cells, NF-κB p65, TNF-α, IL-1β, INF-γ, and Fas, compared to the GG and CG groups (P < 0.05). ConclusionThe results suggest that vitamin D has beneficial effects on T2DM by improving the functions of islet β cells through inhibition of the NF-κB signaling pathway. Therefore, it is suggested that vitamin D supplementation, when used alongside antidiabetic drugs, may more effectively prevent and treat T2DM.

Edible mushroom (Pleurotus cornucopiae) extract vs. glibenclamide on alloxan induced diabetes: sub-acute in vivo study of Nrf2 expression and renal toxicity.

The study aims to compare the action of Pleurotus cornucopiae and glibenclamide on alloxan-induced diabetes and ascertain how an aqueous extract of the edible mushroom regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), oxidative stress biomarkers and renal toxicity in a diabetic male Wistar rat model. Twenty-five adult male Wistar rats were randomly grouped into five groups with five rats per. Group 1 and those in the treatment groups received normal feed and water ad libitum. Group 2 received intraperitoneal administration of alloxan monohydrate (150 mg/kg body weight). Group 3 received alloxan monohydrate and glibenclamide (5 mg/kg body weight bwt), group 4 received alloxan monohydrate plus the extract (250 mg/kg bwt) and group 5 received alloxan monohydrate plus the extract (500 mg/kg bwt). The administration of glibenclamide plus the extract was oral for 14 days. Glibenclamide and the extract lowered blood glucose level, catalase, and glutathione peroxidase activities, increased the superoxide dismutase (SOD) activity in rats with alloxan induced diabetes. The extract at 500 mg/kg bwt reduced the plasma urea and sodium concentration in the treated rats. The extract and glibenclamide could detoxify alloxan and restore its induced renal degeneration and glomeruli atrophy, intra renal hemorrhage and inflammation and oxidative biomarkers through activation of Nrf2 expression. The drug glibenclamide and P. cornucopiae have appreciable hypoglycemic activity and potential to restore the normal renal architecture in the rats, hence they offer similar curative effects. Additionally, the extract at 500 mg/kg bwt activated SOD and Nrf2 expression more than glibenclamide in rats with alloxan-induced diabetes.

Evaluation the Effect of Vernonia amygdalina. Del Leaves Ethanol Extract on Blood Sugar and its Synergism with Glibenclamide in Rats

Antidiabetic activity of Vernonia amygdalina and its possible synergism with glibenclamide was checked. Forty eight rats were used for the research, for hypoglycermic study of V. amygdalina alone, they were grouped into five of six rats each. Group 1 was the negative control and was administered distilled water orally. Groups 2, 3, and 4 were the treatment groups which received 100, 200 and 300 mg/kg body weight of the V. amygdalina extract respectively orally by intubation. Group 5 was the positive control group which received a known antidiabetic drug, glibenclamide. Diabetes was induced with alloxan. For the synergism study, another 18 rats grouped into 3 of six rats each was used. Both groups of glibenclamide only and glibenclamide plus V. amygdalina extract were dosed for 14 days orally by intubation, thereafter were sacrificed and blood collected from heart for analysis. There were 5 replicates grouped by weight throughout the study and both single and synergistic studies had the same controls. Effect of V. amygdalina extract was checked on blood glucose and its possible synergism with glibenclamide. All results in treatment groups were compared with the normal control at statistical confidence of p&lt;0.05. Result shows that V. amygdalina extract reduced blood glucose level in the test groups as dose of extract increased. Combination of V. amygdalina with glibenclamide demonstrated further deduction in blood glucose levels in the treatment rats groups. Therefore addition of V. amygdalina into glibenclamide increased efficacy in the diabetic rats. The interaction between V. amygdalina and glibenclamide in this work was additive and therefore synergistic.

Роль NO и H 2 S в регуляции тонуса церебральных сосудов при хронической болезни почек

Chronic kidney disease (CKD) is a widely spread condition that is a risk factor for the development of cerebrovascular diseases and neurological complications. Currently the mechanisms by which CKD increases the risk of brain damage are poorly understood. In our study, NO- and H2S-mediated changes in the cellular and molecular mechanisms of cerebral artery tone regulation were investigated in male Wistar rats in vivo with a CKD model. CKD was modeled by removal of 5/6 renal tissue at 4 months of age. After 4 months, part of the parietal bone and the dura mater were removed, and the diameter of the arteries was measured under the action of blockers and signaling pathway inhibitors using a microscope. In nephrectomized rats, the reactions of cerebral arteries to the application of acetylcholine (AH) manifested mainly in the form of constriction, while vasodilation predominated in the control group. Sodium nitroprusside led to a dilatation of the arteries, the amplitude of which in rats with CKD was significantly lower compared to the control group. Methylene blue and glibenclamide in rats with CKD led to a slight weakening of reactions to ACh, while in control group rats, the dilatation of arteries was significantly reduced. The degree of dilatation of cerebral arteries on H2S in rats with CKD was significantly less compared to rats in the control group. Propargylglycine caused only slight changes in artery diameter of CKD rats, while in the control group the reaction to propargylglycines was statistically significant. We conclude that the CKD attenuates endothelium-dependent and endothelium-independent NO- and H2S-mediated dilator reactions in cerebral arteries.

Mild hypothermia decreases the total clearance of glibenclamide after low dose administration in rats

Background and purposeLow dose glibenclamide exhibits pleiotropic protective effects in different central nervous system diseases. Previously, we have shown that mild hypothermia enhanced the efficacy of glibenclamide in the cultured cortical neuronal cells. This study aims to evaluate the impact of mild hypothermia on the pharmacokinetics of low dose glibenclamide in rats via its cytochrome P450 2C9 (CYP2C9) metabolic pathway. MethodsMale Sprague-Dawley rats were maintained at 37°C (normothermic group) or cooled to 33°C (hypothermic group). Glibenclamide (33μg/kg) or diclofenac (10mg/kg, a probe drug for assessing the activity of CYP2C9 which involves in glibenclamide and diclofenac metabolism in liver) were intravenously administered at 10min after stabilization of temperature. Plasma samples were collected at 9 different time points. Glibenclamide and diclofenac in sera were separated by liquid chromatography and quantified with tandem mass spectrometry. ResultsCompared with normothermia, mild hypothermia significantly decreased the total clearance of glibenclamide (16.00±4.1–6.72±2.1mL/min/kg; p<0.01), and there was a non-significant trend in a slightly higher half-life, (1.64±0.34–2.71±1.7h, p=0.157). Area under the plasma concentration versus time curve (AUClast) in the hypothermic group was increased (33.2±11–77.8±18hng/mL, p<0.01). Moreover, mild hypothermia reduced the total clearance of diclofenac (10.33±1.53–7.20±1.66mL/min/kg, p<0.01), indicating that the CYP2C9 activity was compromised in reduced temperature. ConclusionMild hypothermia reduced the total clearance of glibenclamide, probably via mediating the activity of CYP2C9. The impact of hypothermia in clinical application of glibenclamide should be considered.

Effect of Calliandra portoricensis extract on the pharmacokinetics of glibenclamide in rats

Effect of Calliandra portoricensis extract on the pharmacokinetics of glibenclamide in rats

Antidiabetic Effect of Aqueous Seed and Endocarp Extracts of King Combined with Glibenclamide in Rats

Antidiabetic Effect of Aqueous Seed and Endocarp Extracts of King Combined with Glibenclamide in Rats

Changes in the pharmacokinetics of glibenclamide in rats with streptozotocin-induced diabetes mellitus

The aim of this study was to investigate the pharmacokinetics of glibenclamide (Gli) administrated orally and intravenously to normal and diabetic rats. The AUC(0–720min) of orally administered Gli in diabetic rats (321.24mgmin/L) was greater than that (57.752mgmin/L) in normal rats. CL (0.019L/min/kg) was significantly slower than that (0.092L/min/kg) of normal rats. The AUC(0–480min) of intravenous Gli in diabetic rats (1528.280mgmin/L) also was significantly greater than that (509.523mgmin/L) in normal rats, and CL was decreased approximately 3-fold. No significant difference in intestinal absorption of Gli was observed between normal and diabetic rats as determined by in situ single-pass intestinal perfusion. The clearance of Diclofenac (a substrate of CYP2C9) was determined to evaluate changes in hepatic drug-metabolizing enzyme activity in rats. The CL in diabetic rats was significantly lower (42.43% decrease) than that in normal rats. Hepatic protein expression of CYP2C9 was measured using Western blot analysis; compared with normal rats, the hepatic protein expression of CYP2A9 was decreased in diabetic rats. Therefore, the slower clearance of Gli in diabetic rats can be attributed primarily to the lower expression of hepatic CYP2C9.

Effects of co—administration of methanol leaf extract of Catharanthus roseus on the hypoglycemic activity of metformin and glibenclamide in rats

Objective To investigate the interacting effects of co-administration of methanol leaf extract of Catharanthus roseus (C. roseus) on the hypoglycemic activity of metformin as well as glibenclamide using experimental rats. Methods Phytochemical analysis as well as acute toxicity and lethality (LD 50) test were carried out on its methanol leaf extract. The alloxan model for experimental induction of diabetes in rats was employed. Six groups comprising five rats each were used. Groups II, III and IV received 250 mg/kg of extract, 100 mg/kg of metformin and 1 mg/kg of glibenclamide respectively, while V and VI were administered metformin-extract and glibenclamide-extract combinations respectively at doses as above. Group I served as negative control and received only distilled water. All administration was done once daily for seven days. Fasting blood glucose was determined at 2, 12, 24, 72 and 168 h using a glucometer. One-way ANOVA with post-hoc tests was used to assess for significant difference due to administration of drug alone and with co-administration of drug and extract. Results The LD 50 was 2 121.32 mg/kg. The phytochemical studies indicated the presence of saponins, tannins, alkaloids, phlotatannins, flavonoids, triterpenoids, reducing sugars, anthraquinones and glycosides. All medicaments significantly reduced blood glucose levels when compared with control alone ( P<0.05) with the highest percentage reduction in blood glucose (64.86%) exhibited by metformin-extract combination. Conclusions The leaf extract of C. roseus significantly increases the hypoglycemic effect of metformin.

Effects of HuangKui capsules on glibenclamide pharmacokinetics in rats

EthnopharmacologyThe main components of HuangKui capsules’ are the total flavonoids extracted from the flowers of Abelmoschus manihot L medic. They have been widely used to treat chronic glomerulonephritis, diabetic nephropathy and nephrotic syndrome. The combination of HuangKui capsules and glibenclamide is a possible therapy for patients with diabetes mellitus and diabetic nephropathy. However, there is no report about effects of HuangKui capsules on the glibenclamide pharmacokinetics till now. Aim of the studyThis study was aimed investigating the effect of HuangKui capsules on pharmacokinetics of glibenclamide in rats. Material and methodsEight rats were administered with an oral dose of HuangKui capsules (0.75gkg−1) once daily for 10 consecutive days. All the rats were administered orally with the glibenclamide (1mgkg−1) before the first time and after the last time given HuangKui capsules. LC–MS/MS was utilized to determine the concentration of glibenclamide in rat plasma and to calculate the corresponding pharmacokinetic parameters. The statistical differences of the two cycles were evaluated by paired-samples t-test. ResultsIn the rats treated with HuangKui capsules and glibenclamide, the t1/2, the time point of maximum plasma concentration (Tmax) of glibenclamide increased obviously (p<0.05) compared with the glibenclamide alone, while maximum plasma concentrations (Cmax), area under the plasma concentration-time curve (AUC(0−t)) decreased significantly (p<0.05). There was no significant difference between other parameters. ConclusionHuangKui capsules can reduce the absorption of glibenclamide and accelerate the metabolism of glibenclamide.

Pharmacodynamic drug interaction study: effect of sertraline on the hypoglucemic action of glibenclamide in rats

The effect of sertraline on glibenclamide control of blood sugar level was determined in normoglycemic and alloxanised rats. Sertraline enhance the hypoglycaemic action in a non-dose dependent fashion in the normoglycaemic and alloxanised rats. Sertraline (40mg/Kg body weight) was more effective in the enhancement of blood sugar lowering effect of glibenclamide than glibenclamide alone and glibenclamide-sertraline (80mg/Kg body weight). Although sertraline enhanced the blood hypoglycaemic activity of glibenclamide in rats the clinical significance of the study is not yet known. Bio-Research Vol. 3(1) 2005: 31-34

Extrapancreatic and pancreatic actions of glibenclamide in rats

The aim of this study was to investigate the influence of glibenclamide on insulin release via insulinotropic gut factors and via a direct action on the pancreas. Maximum peripheral IRI levels appeared 1 minute after intragastric administration of the minimal effective dose of glibenclamide to rats. The corresponding drug levels were high (600 ng/g) in the duodenal mucosa, but low (2 ng/ml) in the peripheral serum. These concentrations were too low to cause insulin release by direct action on the pancreas. Intragastric glibenclamide increased the amount of “duodenal insulin releasing activity” (DIRA) in the mucosa immediately after drug administration. When glibenclamide was dissolved in plasma at a high concentration (1 μg/ml) and then injected into the coeliac trunk of an in-situ rat pancreas preparation, no additional effect on portal IRI levels was measured as compared with injection of serum alone. In contrast significant IRI release was noticed when glibenclamide was dissolved in serum (1 μg/ml) of rats pretreated with the drug intragastrically. The plasma of pretreated rats without addition of glibenclamide was ineffective. The results suggest that glibenclamide may have two effects, one releasing insulin at the pancreas directly, and the other inducing the release of a gastrointestinal factor which amplifies the first effect. Neither glibenclamide nor the factor alone can provoke an IRI release under physiological conditions. The possible importance of these findings for the regulation of insulin secretion is discussed.