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

Abstract

The nano-sized iron oxide (Fe₂O₃-NPs) is one of the most used engineered nanomaterials worldwide. This study investigated the efficacy of natural polyphenol resveratrol (RSV) (20 mg/kg b.wt, orally once daily) to alleviate the impaired sperm quality and testicular injury resulting from Fe₂O₃-NPs exposure (3.5 or 7 mg/kg b.wt, intraperitoneally once a week) for eight weeks. Spermiograms, sexual hormonal levels, oxidative stress indicators, and lipid peroxidation biomarker were assessed. Moreover, the steroidogenesis-related genes mRNA expressions were evaluated. The results showed that RSV substantially rescued Fe₂O₃-NPs-mediated sperm defects. Additionally, the Fe₂O₃-NPs-induced depressing effects on sperm motility and viability were markedly counteracted by RSV. Moreover, RSV significantly restored Fe₂O₃-NPs-induced depletion of testosterone, follicle-stimulated hormone, luteinizing hormone, and testicular antioxidant enzymes but reduced malondialdehyde content. Furthermore, the Fe₂O₃-NPs-induced downregulation of steroidogenesis-related genes (3 β-HSD, 17 β-HSD, and Nr5A1) was significantly counteracted in the testicular tissue of RSV-treated rats. These findings concluded that RSV could limit the Fe₂O₃-NPs-induced reduced sperm quality and testicular injury most likely via their antioxidant activity and steroidogenesis-related gene expression modulation.

Keywords: iron oxide nanoparticles; male sex hormones; oxidative stress; resveratrol; steroidogenesis-related genes.

Figure 1

Transmission electron microscopy diffraction patterns for iron oxide nanoparticles.

Figure 2

Effect of resveratrol (RSV; 20 mg/kg b.wt) and/or iron oxide nanoparticles (Fe₂O₃-NPs 3.5 or 7 mg/kg b.wt) administration for eight weeks on the final body weight (A); gonadosomatic index (B); sperm motility (C); viability (D); concentration (E); and abnormalities (F) of male rats. Data expressed as mean ± SD, n = 9 for each group. Different letters (a, b, c, and d) on columns indicate statistically significant differences at p < 0.05 between the different experimental groups.

Figure 3

The effect of resveratrol (RSV; 20 mg/kg b.wt) and/or iron oxide nanoparticles (Fe₂O₃-NPs 3.5 or 7 mg/kg bwt) administration for eight weeks on the serum levels of male sexual hormones, including testosterone (TES) (A), follicle-stimulating hormone (FSH) (B), and luteinizing hormone (LH) (C) in male rats. Data expressed as mean ± SD, n = 9 for each group. Different letters (a, b, c, and d) on columns indicate statistically significant differences at p < 0.05 between the different experimental groups.

Figure 4

Effect of resveratrol (RSV; 20 mg/kg b.wt) and/or iron oxide nanoparticles (Fe₂O₃-NPs 3.5 or 7 mg/kg b.wt) administration for eight weeks on superoxide dismutase (SOD) (A) catalase (CAT) (B), glutathione peroxidase (GPx) (C), and reduced glutathione (GSH) (D) levels in the testicular tissues of male rats. Data expressed as mean ± SD, n = 9 for each group. Different letters (a, b, c, and d) on columns indicate statistically significant differences at p < 0.05 between the different experimental groups.

Figure 5

Effect of resveratrol (RSV; 20 mg/kg b.wt) and/or iron oxide nanoparticles (Fe₂O₃-NPs 3.5 or 7 mg/kg b.wt) administration for eight weeks on malondialdehyde (MDA) levels in the testicular tissues of male rats. Data expressed as mean ± SD, n = 9 for each group. Different letters (a, b, c, and d) on columns indicate statistically significant differences at p < 0.05 between the different experimental groups.

Figure 6

Effect of resveratrol (RSV; 20 mg/kg b.wt) and/or iron oxide nanoparticles (Fe₂O₃-NPs 3.5 or 7 mg/kg b.wt) administration for eight weeks on mRNA expression of (A) 3 beta-Hydroxysteroid dehydrogenase (3β-HSD), (B) 17-beta hydroxysteroid dehydrogenase (17β-HSD), and (C) Nuclear Receptor Subfamily 5 Group A Member 1 (Nr5A1) in the testicular tissues of male rats. Data expressed as mean ± SD, n = 9 for each group. Different letters (a, b, c, and d) on columns indicate statistically significant differences at p < 0.05 between the different experimental groups.