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

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.

Palliative Effect of Resveratrol against Nanosized Iron Oxide-Induced Oxidative Stress and Steroidogenesis-Related Genes Dysregulation in Testicular Tissue of Adult Male Rats

“…TES is produced chiefly in Leydig cells through a series of enzymatic reactions. First, the steroidogenic acute regulatory (StAR) protein transfers cholesterol to the mitochondria [97]. Then, the mitochondrial cytochrome P450scc converts cholesterol into pregnenolone.…”

Association of Hypoglycemia with Biomarkers of Oxidative Stress and Antioxidants: An Observational Study

“…It is well established that hyperglycemia induces an increase in pro-inflammatory cytokines and oxidative biomarkers [ 6 ]. It has also been reported that combined treatment with metformin and chitosan-stabilized selenium nanoparticles, which serve as antioxidants, could improve diabetic complications by reducing oxidative stress and restoring glucose homeostasis in high-fat diet feed with low-dose streptozotocin (HFD-STZ) diabetic rats [ 24 , 25 , 26 ]. On the other hand, hypoglycemia is known to induce an increase in pro-inflammatory mediators, but its relationship with OS is not well elucidated.…”

Concerns with Male Infertility Induced by Exposure to Titanium Nanoparticles and the Supporting Impact of Pelargonium graveolens Essential Oil: Morphometric Records in Male-Wistar Rats

“…In contrast, the MDA level was promoted, and the levels of antioxidant-related enzymes SOD, GPx, and CAT were reduced, resulting in lipid peroxidation and cell apoptosis. This increased ROS in response to TiO 2 NPs exposure also significantly impacts sperm because of the presence in the cell membrane of various polyunsaturated fatty acids [ 47 ]. According to growing data, ROS emission can disrupt the blood–testis barrier, worsening sperm dysfunction and impairing fertility [ 48 ].…”