Erythritol attenuates testicular dysfunction in diabetic rat via suppression of oxidative stress, inflammation and apoptosis.

Hyperglycemia -induced oxidative stress and inflammation have been closely associated with diabetes complications including testicular dysfunction. Conversely, reducing blood glucose and/or use of antioxidant have been associated with reduced diabetes complications. The present study investigated the effect of erythritol (which has both antioxidant and blood glucose lowering function) on diabetes -induced testicular dysfunction in rats. Thirty male Wistar rats (170-200g) were randomly divided into 5 groups: 1) control; 2) erythritol; 3) diabetic; 4) diabetic + erythritol 1000 mg/kg; and 5) diabetic + metformin 300 mg/kg. After 8 weeks of treatment period, blood sample, testes and epididymis were collected for reproductive hormones, biochemical and histological examinations, and sperm analysis respectively. There was a significant (p < 0.05) decrease in sperm count, sperm motility, sperm morphology and serum reproductive hormones (Follicle stimulating hormone (FSH), Leutinizing hormone (LH), testosterone and gonadotropin releasing hormone (GnRH)) of diabetes rat compared to control. Also, diabetes rat showed increase in sperm and testicular malonaldehyde (MDA) and decrease in sperm and testicular superoxide dismutase (SOD) activity and glutathione (GSH) level. Further, diabetes rat showed reduced testicular weight, decreased testicular 17ß-HSD and 3ß-HSD activity and testicular histo-architectural alteration which were accompanied by decrease testicular vascular endothelial growth factor (VEGF) and concomitant increase in testicular myeloperoxidase activity and level of caspase 3. The present results indicates that induction of diabetes in rat causes reduction in the level of reproductive hormones (Testosterone, LH and FSH) as well as sperm and testicular oxidative stress causing abnormal sperm parameters, and biochemical and histo-architectural alterations in the testes of rats. In addition, the present results suggest that erythritol administration reduced blood glucose and ameliorated hyperglycemia -induced oxidative stress -mediated alterations in both sperm and testes of diabetes rat. Further, the present study suggests that erythritol improved testicular oxidative stress, inflammation and apoptosis by up-regulating VEGF.

Blood glucose lowering and anti-oxidant potential of erythritol: An in vitro and in vivo study.

Background: Diabetes is a major cause of death worldwide and Nigeria is not an exception. The quest to lower sugar levels has become a major factor in the management of diabetes; this has occasioned the use of substitutes for refined sugar in beverages. Erythritol is a natural sweetener gaining immense interest in recent times. Like metformin, erythritol has shown hydroxyl radical scavenging ability and has metabolic profile suitable for diabetics. Therefore, the blood glucose-lowering and anti-oxidant properties of erythritol under in vitro and in vivo systems were accessed. Methods: Radical scavenging assay (ABTS and DPPH) and inhibition of carbohydrate digestive enzymes (alpha-amylase and alpha-glucosidase) were employed to determine in vitro anti-oxidant and glucose regulatory function of erythritol respectively. Molecular docking studies were performed between 3D structures of human pancreatic alpha-amylase and alpha-glucosidase, isomaltase from saccharomyces cerevisiae with erythritol. The drug-like activity of erythritol was also assessed.Thereafter, we investigated the effect of erythritol on blood glucose and antioxidant status of normal and streptozocin- nicotinamide-induced diabetes rats which were grouped into five (n = 5); Normal, Ery (normal and administered erythritol), Db (diabetic control), Db + Ery (diabetic and administered erythritol), and Db + Met (diabetic and administered metformin). Results: Erythritol showed a considerable radical scavenging activity and an ability to inhibit alpha-amylase and alpha-glucosidase in vitro. Also, a significant reduction in glucose intolerance, blood glucose and hemoglobin A1c levels and improved antioxidant level was seen in erythritol-treated diabetic rats. Conclusion: Erythritol showed anti-oxidant activity, alpha amylase and glucosidase enzyme inhibition property, improved antioxidant status and ameliorated blood glucose, HbA1c, and glucose intolerance following diabetes.

Sodium acetate prevents nicotine-induced cardiorenal dysmetabolism through uric acid/creatine kinase-dependent pathway.

BACKGROUND: Cigarette smoking or nicotine replacement therapy has been associated with cardiometabolic disorders (CMD). Hyperuricemia has been implicated in the pathogenesis of CMD and cardiorenal dysfunction. Gut microbiota-derived short chain fatty acids (SCFAs) have been reported to have beneficial glucoregulatory and cardiorenal protective effects. This study aimed at investigating the effect of acetate, a gut-derived SCFA, on nicotine-induced CMD and associated cardiorenal dysmetabolism. MATERIALS AND METHOD: Twenty-four male Wistar rats (n = 6/group) were grouped as: vehicle (p.o.), nicotine-exposed (1.0 mg/kg; p.o.), and sodium acetate-treated (200 mg/kg; p.o.) with or without nicotine exposure daily for 6 weeks. Glucose regulation was evaluated by oral glucose tolerance test and homeostatic model assessment of insulin resistance. Cardiac and renal triacylglycerol (TG), lactate, nitric oxide (NO), uric acid (UA) levels, lactate dehydrogenase (LDH), creatine kinase (CK), adenosine deaminase (ADA), and xanthine oxidase (XO) activities were measured. RESULTS: The CMD were confirmed in the nicotine-exposed rats that exhibited lower body weight, insulin resistance, endothelial dysfunction, glucose intolerance, increased cardiac and renal TG, TG/HDL-cholesterol, UA, lactate, lipid peroxidation, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, LDH, CK, ADA and XO activities. Concurrent treatment with acetate prevented nicotine-induced glucometabolic and cardiorenal alterations. CONCLUSION: In summary, these results implied that nicotine exposure caused glucometabolic dysregulation and surplus lipid deposit in the heart and kidney through increased UA production and CK activity. Therefore, oral acetate administration prevents cardiorenal lipotoxicity and glucometabolic dysregulation via suppression of UA production and CK activity in nicotine-exposed rats.