Chitosan-Stabilized Selenium Nanoparticles and Metformin Synergistically Rescue Testicular Oxidative Damage and Steroidogenesis-Related Genes Dysregulation in High-Fat Diet/Streptozotocin-Induced Diabetic Rats.

Yasmina M Abd El-Hakim,Manal Ewaiss Hassan,Mohamed A Nassan,Safaa I Khater,Ahmed Hamed Arisha,Mohamed M M Metwally,Amany Abdel-Rahman Mohamed

doi:10.3390/antiox10010017

Abstract

Background: this study examined the metformin (MF) and/or chitosan stabilized selenium nanoparticles (CH-SeNPs) efficacy to alleviate the male reproductive function impairment in a high-fat diet feed with low-dose streptozotocin (HFD/STZ) induced type 2 diabetes mellitus (T2DM) diabetic rat model. Methods: control non-diabetic, HFD/STZ diabetic, HFD/STZ+MF, HFD/STZ+CH-SeNPs, and HFD/STZ+MF+CH-SeNPs rat groups were used. After 60 days, semen evaluation, hormonal assay, enzymatic antioxidant, lipid peroxidation, testis histopathology, and the steroidogenesis-related genes mRNA expressions were assessed. Results: in the HFD/STZ diabetic rats, sperm count and motility, male sexual hormones, and testicular antioxidant enzymes were significantly reduced. However, sperm abnormalities and testicular malondialdehyde were significantly incremented. The steroidogenesis-related genes, including steroidogenic acute regulatory protein (StAr), cytochrome11A1 (CYP11A1), cytochrome17A1 (CYP17A1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), and the mitochondrial biogenesis related genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGCα) and sirtuin (SIRT), were significantly downregulated in the HFD/STZ diabetic rats. However, CYP19A1mRNA expression was significantly upregulated. In contrast, MF and/or CH-SeNPs oral dosing significantly rescued the T2DM-induced sperm abnormalities, reduced sperm motility, diminished sexual hormones level, testicular oxidative damage, and steroidogenesis-related genes dysregulation. In the MF and CH-SeNP co-treated group, many of the estimated parameters differ considerably from single MF or CH-SeNPs treated groups. Conclusions: the MF and CH-SeNPs combined treatment could efficiently limit the diabetic complications largely than monotherapeutic approach and they could be considered a hopeful treatment option in the T2DM.

Highlights

Diabetes mellitus (DM) is a metabolic condition that is determined by continuous blood glucose increases due to impaired production and/or insulin action [1]
The preparation and characterization of CH selenium nanoparticles (SeNPs) have been previously described in our earlier study [38]
The high-fat diet/streptozotocin (HFD/STZ) diabetic group displayed a significant decline (p < 0.001) in motility percentage, sperm concentration, and live sperm percentage6 of by17−58.82%, and 57.28%, respectively, when compared to the control group, as presented in F

Summary

Introduction

Diabetes mellitus (DM) is a metabolic condition that is determined by continuous blood glucose increases due to impaired production and/or insulin action [1]. Epidemiological studies have shown that approximately 50% of diabetic patients suffer from various levels of reproductive disorders, which include declined libido and impotence, difficulty ejaculating, erectile dysfunction, and reduced infertility [6,7,8]. Numerous studies in diabetic men and diabetic animal models showed that infertility was associated with altered spermatogenesis, degenerative testicular changes, disturbed glucose metabolism in blood testes barrier, and reduced testosterone (TES) secretion [9,10]. Long-term elevated blood glucose induces an excessive reactive oxygen (ROS) production that can interrupt the oxidant-antioxidant system equilibrium [12]. Excessive ROS release and the resulting oxidative stress promote germ cell death and interfere with the process of spermatogenesis [13]

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