Glibenclamide Increases Nitric Oxide Levels and Decreases Oxidative Stress in an In Vitro Model of Preeclampsia.
Antioxidants (Basel, Switzerland)
(1) Background: The bioavailability of nitric oxide (NO) and oxidative stress are important events related to the pathophysiology of preeclampsia (PE). In this present study, we aimed to evaluate the antioxidant effect of glibenclamide (GB) on the NO synthesis, oxidative stress, and antioxidant capacity in endothelial cells incubated with plasma from preeclamptic (PE) and normotensive pregnant women (NT). (2) Methods: Human umbilical vein endothelial cells (HUVECs) were incubated with a plasma pool from 10 NT and 10 PE pregnant women; NO/NOx quantification and ROS levels were assessed by a fluorescence compound; lipid peroxidation was evaluated employing thiobarbituric acid (TBA); and total antioxidant capacity was measured by ferric reduction ability power (FRAP) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). (3) Results: We found that endothelial cells incubated with plasma from PE showed lower NO and NOx levels compared with the NT group. However, GB treatment increased these levels, as well as the antioxidant capacity. Furthermore, a decrease was observed in ROS generation and lipid peroxidation (4) Conclusions: The GB treatment exerted a positive effect on the NO/NOx production by HUVEC incubated with plasma from NT and PE pregnant women, as well as in the reduction in oxidative stress and increase in the antioxidant capacity.
10.3390/antiox11081620
Effects of glibenclamide and troxerutin on the sperm parameters and histopathological changes of testis in streptozotocin-induced diabetic male rats: An experimental study.
International journal of reproductive biomedicine
Background:Oxidative stress is a major contributor to diabetes mellitus (DM), which leads to testicular damage and infertility. Objective:The aim of this study was to investigate the effects of glibenclamide (GL) as a chemical medicine and troxerutin (TR) as an herbal agent on sperm parameters and histopathological changes of testis in diabetic male rats. Materials and Methods:Forty male Wistar rats (230-260 gr) were randomly divided into 5 groups (n = 8/each), including control, diabetic (D), GL, TR, and GL+TR. DM was induced by the administration of 60 mg/kg streptozotocin intraperitoneally. The groups were treated with 5 mg/kg/day of GL or 150 mg/kg/day of TR via oral gavage for 4 wk. In the final stage of the treatment, blood sampling was done for biochemical analysis. The rats were then sacrificed and their left testis and epididymis were dissected for sperm analysis, histopathology, and morphometric assessment. Results:A significant decrease in the number, motility, viability, maturity, and chromatin quality of sperm was found in diabetic rats compared to control group. (p 0.001). DM also increased the malondialdehyde level and decreased the level of the serum's total antioxidant capacity compared to the control group (p 0.001). Furthermore, we observed a significant difference in seminiferous tubule diameter, germinal epithelium height, and testicular histological abnormalities in diabetic rats compared to control group (p 0.001). Administration of GL, TR, and their combination improved the above-mentioned parameters, and treatment with TR provided a higher improvement (p 0.001). Conclusion:According to these findings, it can be concluded that TR plays a more influential role than GL to treat diabetic-induced infertility.
10.18502/ijrm.v21i2.12803
Comparative effects of glibenclamide, metformin and insulin on fetal pancreatic histology and maternal blood glucose in pregnant streptozotocin-induced diabetic rats.
African health sciences
BACKGROUND:Oral hypoglycemic agents use during pregnancy was assumed to cause fetal macrosomia and skeletal deformities, and maternal complications due to significant transfer across placenta or ineffective control of blood glucose. OBJECTIVE:This study investigated effects of insulin, metformin and glibenclamide on maternal blood glucose; and fetal crown-rump length, gross malformation and pancreatic histology in pregnant streptozotocin-induced diabetic rats. METHODS:Twenty-five pregnant rats of groups 1 to 5 as normal and diabetic controls; and diabetic treated with insulin, metformin and glibenclamide were used. Experimental GDM was induced using 45 and 35mg/Kgbw of intraperitoneal streptozotocin. RESULTS:Metformin, Insulin and Glibenclamide significantly reduced maternal glucose by 140.6mg/dL, 103.2mg/dL and 98.54mg/dl; respectively and showed islets with regular interlobular ducts, islets with some irregular interlobular ducts, and islets with many irregular interlobular ducts in histological fetal pancreatic photomicrographs respectively. This depicts metformin having highest ameliorative effect. There were no significant differences in maternal and fetal body weights, maternal blood glucose between diabetic groups, and fetal gross examination. CONCLUSION:At the doses used in this research, metformin and glibenclamide showed no adverse effects on maternal and fetal features in the treatment of GDM. Thus, they can be used as safe and inexpensive alternatives to insulin.
10.4314/ahs.v19i3.25
Glibenclamide and metfoRmin versus stAndard care in gEstational diabeteS (GRACES): a feasibility open label randomised trial.
BMC pregnancy and childbirth
BACKGROUND:Metformin is widely used to treat gestational diabetes (GDM), but many women remain hyperglycaemic and require additional therapy. We aimed to determine recruitment rate and participant throughput in a randomised trial of glibenclamide compared with standard therapy insulin (added to maximum tolerated metformin) for treatment of GDM. METHODS:We conducted an open label feasibility study in 5 UK antenatal clinics among pregnant women 16 to 36 weeks' gestation with metformin-treated GDM. Women failing to achieve adequate glycaemic control on metformin monotherapy were randomised to additional glibenclamide or insulin. The primary outcome was recruitment rate. We explored feasibility with uptake, retention, adherence, safety, glycaemic control, participant satisfaction and clinical outcomes. RESULTS:Records of 197 women were screened and 23 women randomised to metformin and glibenclamide (n = 13) or metformin and insulin (n = 10). Mean (SD) recruitment rate was 0.39 (0.62) women/centre/month. 9/13 (69.2%, 95%CI 38.6-90.9%) women adhered to glibenclamide and all provided outcome data (100% retention). There were no episodes of severe hypoglycaemia, but metformin and insulin gave superior glycaemic control to metformin and glibenclamide, with fewer blood glucose readings <3.5 mmol/l (median [IQR] difference/woman/week of treatment 0.58 [0.03-1.87]). CONCLUSIONS:A large randomised controlled trial comparing glibenclamide or insulin in combination with metformin for women with GDM would be feasible but is unlikely to be worthwhile, given the poorer glycaemic control with glibenclamide and metformin in this pilot study. The combination of metformin and glibenclamide should be reserved for women with GDM with true needle phobia or inability to use insulin therapy. TRIAL REGISTRATION:www.clinicaltrials.gov registration number:NCT02080377 February 11th 2014.
10.1186/s12884-017-1505-3
Insulin Detemir Versus Glibenclamide in Gestational Diabetes Mellitus: A Retrospective Cohort Study.
The Israel Medical Association journal : IMAJ
BACKGROUND:Treatment of gestational diabetes mellitus (GDM) has been shown to improve both maternal and neonatal outcomes. For women with GDM who require glucose-lowering medication, insulin is regarded as the drug of choice by most medical societies. Oral therapy, with metformin or glibenclamide, is a reasonable alternative in certain medical circumstances. OBJECTIVES:To compare the efficacy and safety of insulin detemir (IDet) vs. glibenclamide for GDM when glycemic control cannot be achieved through lifestyle modification and diet. METHODS:We conducted a retrospective cohort analysis of 115 women with singleton pregnancy and GDM treated with IDet or glibenclamide. GDM was diagnosed via the two-step oral glucose tolerance test (OGTT) of 50 grams glucose, followed by 100 grams. Maternal characteristics and outcomes (preeclampsia and weight gain) and neonatal outcomes (birth weight and percentile, hypoglycemia, jaundice, and respiratory morbidity) were compared between groups. RESULTS:In total, 67 women received IDet and 48 glibenclamide. Maternal characteristics, weight gain, and the incidence of preeclampsia were similar in both groups. Neonatal outcomes were also similar. The proportion of large for gestational age (LGA) infants was 20.8% in the glibenclamide group compared to 14.9% in the IDet group (P = 0.04). CONCLUSIONS:In pregnant women with GDM, glucose control on IDet yielded comparable results as on glibenclamide, except for a significantly lower rate of LGA neonates.
Exposure to low levels of antidiabetic glibenclamide had no evident adverse effects on intestinal microbial composition and metabolic profiles in amphibian larvae.
Environmental science and pollution research international
Unmetabolized human pharmaceuticals may enter aquatic environments, and potentially exert adverse effects on the survival of non-target organisms. Here, Pelophylax nigromaculatus tadpoles were exposed to different concentrations of antidiabetic glibenclamide (GLB) for 30 days to evaluate its potential ecotoxicological effect in amphibians using intestinal microbiomic and metabolomic profiles. The mortality rate of GLB-exposed groups appeared to be lower than that of the control group. Despite not being statistically significant, there was a tendency for a decrease in intestinal microbial diversity after exposure. The relative abundance of bacteria phylum Firmicutes was shown to decrease, but those of other phyla did not in GLB-exposed tadpoles. Some potentially pathogenic bacteria (e.g., Clostridium, Bilophila, Hafnia) decrease unexpectedly, while some beneficial bacteria (e.g., Akkermansia, Faecalibacterium) increased in GLB-exposed tadpoles. Accordingly, GLB-induced changes in intestinal microbial compositions did not seem harmful to animal health. Moreover, minor changes in a few intestinal metabolites were observed after GLB exposure. Overall, our results suggested that exposure to low levels of GLB did not necessarily exert an adverse impact on amphibian larvae.
10.1007/s11356-023-30823-y
Effects of oral glibenclamide versus subcutaneous insulin on perinatal outcome of patients with gestational diabetes mellitus: A randomized clinical trial.
Obstetric medicine
Background:The first-line treatment for gestational diabetes mellitus remains insulin, but oral hypoglycemic agents are easier and cheaper to use. The aim of the current study was to compare the efficacy and safety of oral glibenclamide and subcutaneous insulin on the serum glucose control and perinatal outcome of patients with gestational diabetes mellitus. Materials and methods:This randomized clinical trial was conducted during a 2-year period from 2017 to 2019 in two tertiary healthcare centers in Shiraz, Iran. We included 84 singleton pregnancies between 24 and 34 weeks of gestation diagnosed with gestational diabetes mellitus. Patients were randomly assigned to oral glibenclamide ( = 44) or subcutaneous insulin ( = 40) according to a standard protocol and followed until delivery. The primary endpoint was to compare the glycemic level of patients, and the secondary outcomes included pregnancy adverse events and neonatal complications such as preeclampsia, preterm and premature rupture of membranes, preterm labor, placental abruption, maternal hypoglycemia, birth weight, neonatal hypoglycemia, hyperbilirubinemia, respiratory distress syndrome, and neonatal intensive care unit admission. Results:The two study groups had comparable baseline characteristics. After treatment, the two study groups were comparable regarding fasting blood glucose ( = 0.398) and 2 h postprandial glucose ( = 0.085). There was no significant difference between the two groups regarding the rate of preeclampsia ( = 0.250), preterm rupture of membranes ( = 0.998), preterm labor ( = 0.495), hypoglycemia ( = 0.476), and abruption ( = 0.815). There was no significant difference between the two study groups in birth weight ( = 0.863) and the Apgar score at 1 ( = 0.190) and 5 min ( = 0.055). The rates of neonatal adverse events including hypoglycemia ( = 0.999), hyperbilirubinemia ( = 0.160), neonatal intensive care unit admission ( = 0.852), and respiratory distress syndrome ( = 0.665) were comparable between the two groups. Conclusion:The results of the current study demonstrate that oral glibenclamide is as effective and safe as subcutaneous insulin in glycemic control and maternal and neonatal outcomes in women with gestational diabetes mellitus. Thus, it could be used as first-line treatment of gestational diabetes mellitus.
10.1177/1753495X221100167
Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial.
Sénat Marie-Victoire,Affres Helene,Letourneau Alexandra,Coustols-Valat Magali,Cazaubiel Marie,Legardeur Helene,Jacquier Julie Fort,Bourcigaux Nathalie,Simon Emmanuel,Rod Anne,Héron Isabelle,Castera Virginie,Sentilhes Loic,Bretelle Florence,Rolland Catherine,Morin Mathieu,Deruelle Philippe,De Carne Celine,Maillot François,Beucher Gael,Verspyck Eric,Desbriere Raoul,Laboureau Sandrine,Mitanchez Delphine,Bouyer Jean,
JAMA
Importance:Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes. Objective:To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes. Design, Settings, and Participants:The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation. Interventions:Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations. Main Outcomes and Measures:The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval. Results:Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, -∞ to 10.5%; P=.19). Conclusion and Relevance:This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment. Trial Registration:clinicaltrials.gov Identifier: NCT01731431.
10.1001/jama.2018.4072
Oral administration of proniosomal glibenclamide formulation protects testicular tissue from hyperglycemia fluctuations and ROS via pathway.
Heliyon
Type 2 diabetes causes high blood sugar due to insulin malfunction and is linked to male infertility. Using proniosomes can enhance the effectiveness of Glibenclamide, a medication that stimulates insulin secretion. In our study, male rats with diabetes were treated with GLB with or without proniosomal for 14 days. Proniosomal formulations maintained glucose levels prevented weight loss and showed normal testicular tissue. GLB-proniosomal reduces ROS caused by T2DM through Nrf2, HO-1 pathway and increases CAT, SOD, and GSH production in response to insulin and glucose uptake. The reference and proniosomal treatments showed CAT and SOD significant enzymatic elevation compared to the positive and negative control. CAT significantly correlated with Gpx4 expression with = 0.0169 and r = 0.98; similarly, the enzymatic activity of SOD also showed a positive correlation between the average glucose levels (r = 0.99 and P = 0.0037). Intestinally, GSH analysis revealed that only proniosomal-GLB samples are significantly elevated from the positive control, with a value of 0.0210. The data showed proniosomal-GLB was more effective than pure GLB, confirmed by higher Nrf2 (2.050 folds), HO-1 (2.148 folds), and GPx4 (1.9 folds) transcript levels relative to the control with less sample diversity compared to the reference samples, indicating proniosomal stabilized GLB in the blood. Administering GLB and proniosomes formulation has effectively restored testicular function and sperm production in diabetic rats by regulating ROS levels and upregulating anti-ROS in response to glucose uptake. These findings may lead to better treatments for diabetic patients who have infertility issues.
10.1016/j.heliyon.2024.e31283
Long-term follow-up of children with in utero exposure to sulfonylurea medications.
Obesity science & practice
BACKGROUND:Offspring born to mothers with gestational diabetes mellitus (GDM) are more likely to have negative neurodevelopmental health outcomes, early obesity, type 2 diabetes, and metabolic syndrome in childhood, adolescence, and adulthood. Standard of care management for GDM and type 2 diabetes mellitus during pregnancy is insulin, but oral sulfonylurea use is increasing, and these medications cross the placenta. Literature on treatment with sulfonylureas for maternal GDM has focused on maternal glycemic control and neonatal outcomes. Studies that have evaluated the long-term outcomes of children exposed to sulfonylureas in utero are limited. OBJECTIVE:This study evaluated anthropometric and neurodevelopmental outcomes of 55 children (ages 5-10) born to mothers with diabetes during pregnancy treated with sulfonylurea or insulin. METHODS AND RESULTS:A group of 25 sulfonylurea-exposed and 30 insulin-exposed participants were age- and sex-matched between groups. No significant differences were identified in z-scores for body mass index (BMI), waist circumference, skinfold measurements, and body fat or rates of overweight/obese BMI between groups. On performance-based cognitive assessment, the sulfonylurea-exposed group had significantly lower scores on inhibition ( = 0.043). CONCLUSION:In summary, children with in utero sulfonylurea exposure had similar physical measurements compared to children with insulin exposure and lower performance on a measure of executive function (inhibition), which is associated with adverse health outcomes.
10.1002/osp4.488