Effect of Hesperetin Treatment on Blood Glucose Level, Spermatozoa Quality, and Spermatozoa Quantity in Alloxan-Induced Diabetic Mice

Abstract

Male infertility has occurred rapidly in the last few decades, primarily in developing countries. An antioxidant, hesperetin is a flavonoid that is found in abundance in orange peels. The aims of this research were to determine the effect of hesperetin on blood sugar levels, spermatozoaquality, and spermatozoa quantity. The research structure included induction of diabetes mellitus and treatment for 8 weeks, followed bydetermination of blood sugar levels, spermatozoa quality, and spermatozoa quantity. Hesperetin has the ability to restore blood sugar levels, spermatozoa quantity, seminiferous tubules diameter, and testicular weight, volume, and germinal epithelial layer thickness with significant difference from the normal control group. Hesperetin did not fully restore spermatozoa motility, viability, and morphology with significant difference from the normal control group, nor from the positive control group. However, overall, hesperetin decreased blood glucose levels, increased spermatozoa quantity, and improved the spermatozoa quality in alloxan-induced diabetes mellitus mice. Dose-dependent activity was observed with the optimum dose at 200 mg/kg body weight.

Effect of honey bee venom on the histological changes of testes and hormonal disturbance in diabetic mice

“…Changes in the histological structure of the testes are observed in male fertility cases that are directly linked to T2DM. The histological alterations of the testes include marked reduction of Sertoli and Leydig cells with wide interstitial space, reduction in the diameter of the seminiferous tubules and changing of their shape, degeneration of spermatogonia and spermatocyte with seminiferous vocalization, and reduction the spermatid in the seminiferous tubules' lumen [40,43,46,49]. The results of these studies are in line with the present study result.…”

“…Alteration of sperm quality is another consideration involved in developing infertility in diabetic conditions. Several studies identified remarkable deterioration of sperm characters in response to T2DM, including reduction of sperm viability and motility associated with elevated dead sperm and abnormal morphology, which consequently declined the quality of sperm [40,43,46]. These results are aligned with this study's results.…”

Clinical applications and mechanism insights of natural flavonoids against type 2 diabetes mellitus

“…In recent studies, hesperetin has demonstrated its potential in restoring blood glucose levels in animal models of diabetes. In one study, hesperetin was administered to AID mice, resulting in a significant improvement in blood glucose levels [ 208 ]. Another study focused on the use of hesperetin extracted from Trifolium alexandrinum , a plant belonging to the Fabaceae family, for the treatment of T2DM in rats [ 209 ].…”

Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review

“…Male albino Wistar rats -Reduction in glucose plasma and increase in insulin levels similar to glibenclamide -Recuperation of pancreatic β-cells -Improvement in glucokinase activity and glucose-6-phosphate dehydrogenase -Inhibition of hepatic gluconeogenesis-decrease in the level of gluconeogenic enzymes-glucose-6-phosphatase and fructose-1,6-bisphosphatase -Increased glycogen content in hepatocytes -Antioxidant-increase in activity of enzymic antioxidants -Anti-hyperlipidemic effect-enhanced insulin secretion, which led to a reduction in cholesterol synthesis and due to the ability of hesperetin to bind bile acids, which resulted in a decrease in the cholesterol absorption -Protective effect on hepatic damage -Renoprotective effect [152] Wistar rats -Attenuation of gluconeogenesis by inhibition of mitochondrial pyruvate carrier, uncoupling of mitochondrial oxidative phosphorylation, inhibition of mitochondrial respiratory chain at Complex I, and deviation of NADH supply for gluconeogenesis and mitochondria due to a prooxidant action, deviation of glucose 6-phosphate for glucuronidation reactions [153] Adult male Wistar albino rats -Reduction of plasma glucose because of the increased release of insulin from the existing β-cells and/or regenerated β-cells of the pancreas, restored insulin sensitivity or inhibition of intestinal absorption of glucose, or enhanced the utilization of glucose by peripheral tissues -Improved lipid profile -Improved pancreatic islets' morphology [154] Male mice -Anti-hyperglycemic-increased insulin production and reduced blood glucose levels [155] Wistar rats -Anti-hyperglycemic-decrease in glucose levels -Antioxidant-increase in antioxidant enzymes-SOD, CAT, GSH, GPx activity -Anti-inflammatory-decrease in pro-inflammatory cytokines levels-TNF-α, IL-17 -Anti-apoptotic-suppression of caspase-3 and maintenance of mitochondrial membrane potential [156] In vitro In silico -α-glucosidase inhibition [157] In vitro In silico -Dipeptidyl peptidase-4 inhibition [143] HepG2 cells -Increase in protein level and direct activation of SIRT1, which was accompanied by induction of AMPK phosphorylation [158] RAW264.7 cells -Inhibitory effect on oxidative stress and inflammation induced by AGEs [159] Male Sprague Dawley rats -Up-regulation and Increased Glo-1 enzymatic activity -Anti-inflammatory-decreased level of pro-inflammatory cytokines (IL-1β, TNF-α) -Enhancement of Nrf2/ARE pathway [160] The Importance of Hesperidin and Hesperetin Modes of Action in DM Oxidative stress is a major factor contributing to DM pathogenesis. It affects two mechanisms, which are improperly working in this condition-insulin secretion and insulin action [161,162].…”