Exposure to Zinc Oxide Nanoparticles Induces Neurotoxicity and Proinflammatory Response: Amelioration by Hesperidin.

Zinc oxide nanoparticles (ZnONPs) are widely used in food packaging and may enter the body directly if exposed. Hereby, in this study, the oral administration was selected as the route of exposure for rats to nanoparticles and the effect of hesperidin (HSP, 100 mg/kg bwt) was evaluated on ZnONP (600 mg/kg bwt)-induced neurotoxicity in rats. ZnONPs were characterized using transmission electron microscopy. Neurotoxicity was observed as seen by elevation in serum inflammatory markers including tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1ß), interleukin-6 (IL-6), C-reactive protein (CRP), and activities of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH) content in rat brains. Pretreatment of rats with HSP in ZnONP-treated group elevated activities of antioxidant enzymes. HSP also caused decrease in TNF-α, IL-1ß, IL-6, and CRP levels which was higher in the ZnONP-treated group. The results suggest that HSP augments antioxidant defense with anti-inflammatory response against ZnONP-induced neurotoxicity. The increased antioxidant enzymes enhance the antioxidant potential to reduce oxidative stress.

Sodium Selenite Protects Against Silver Nanoparticle-Induced Testicular Toxicity and Inflammation.

Metal nanomaterials hold great potential and play an important role in consumer products. However, the increasing use of nanomaterials has raised concern over inadvertent exposure and potential risks for human health and the environment. Henceforth, in vivo testing of nanoparticles and protection against its toxicity is required. Using rat as an animal model, effect of sodium selenite (Se), an essential trace element, on rat testes exposed to silver nanoparticles (AgNPs) was evaluated. Male rats were treated with AgNPs (5 mg/kg/b.w) i/p or Se (0.2 mg/kg/b.w) by gavage. AgNP administration decreased Glutathione (GSH) levels and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and increased levels of malondialdehyde (MDA) and expression of interleukin-1 beta (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α). However, treatment with Se increased GSH levels and activities of SOD, CAT, and GPx compared with AgNP-treated group and decreased the level of MDA and inflammatory biomarkers significantly (p < 0.05) as compared with AgNP-treated group. Light microscopic analyses also revealed that AgNP induced histopathological changes in testes tissue. Further, protection by Se on biochemical results was confirmed by alleviation of the histopathological changes in the tissue. Results show the adverse effects of AgNPs on the male reproductive tract, particularly spermatogenesis, and suggest that Se possesses significant potential in reducing AgNP-induced testicular toxicity.

Estradiol affects androgen-binding protein expression and fertilizing ability of spermatozoa in adult male rats.

The estrogenicity of certain environmental pollutants is being increasingly correlated to decline in sperm counts and fertility of the males. Qualitative effects, if any, of estrogen(s) on terminal differentiation of spermatids have been less reported. The present study suggests that exposure to estrogen(s) can also alter the status of condensed chromatin in testicular spermatozoa and reduce their fertilizing potential. A significant reduction was evident in the serum gonadotropins, testosterone, weights of reproductive organs, sperm counts and litters sired by male rats after 10 days of estradiol exposure to a dose of 0.1mg/kg/day. Estradiol treatment led to retardation of in vitro decondensation rates of sperm chromatin, reduction in the uptake of acridine orange dye by chromatin, reduction in susceptibility of chromatin to acid denaturation in vitro, reduced uptake of thiol reactive monobromobimane dye and reduced levels of immunoreactive protamine 1 in caput epididymal sperms. Concomitantly, testicular levels of immunoreactive protamine 1, transition proteins 1/2 and cyclic adenosyl response element modulator-tau (CREMtau) were significantly reduced whilst their mRNA levels were unaffected after estradiol treatment. A significant increase was observed in the testicular mRNA levels of androgen-binding protein (ABP) in estradiol treated sires. An inverse correlation was observed between ABP mRNA levels and uptake of acridine orange by estradiol treated caput sperm chromatin. The results suggest that estradiol-induced increase in ABP mRNA underlies the mechanism(s) involved in the reduction in levels of certain proteins involved in nuclear chromatin condensation during spermiogenesis.

Effects of tamoxifen citrate on gene expression during nuclear chromatin condensation in male rats.

AIM: To evaluate the effects of tamoxifen citrate on gene expression during nuclear chromatin condensation in male rats. METHODS: The effects of an oral dose of 0.4 kg/(kg.d) tamoxifen citrate on rates of in vitro chromatin decondensation, acridine orange (AO) dye uptake, concentration of thiol-groups, levels and/or expression of transition proteins 1, 2 (TP1, TP2), protamine 1 (P1), cyclic AMP response element modulator-tau (CREMtau), androgen-binding protein (ABP) and cyclic adenosine 3',5' monophosphate (cAMP) were evaluated after 60 days of exposure in adult male rats. Controls received the vehicle. RESULTS: Tamoxifen citrate enhanced the rates of chromatin decondensation, increased AO dye uptake and reduced free thiols in caput epididymal sperms and reduced the levels of TP1, TP2, P1, and CREMtau in the testis, while cAMP was unaffected. P1 deposition was absent in the sperm. The transcripts of TP1, TP2 were increased, of P1 and ABP decreased, while those of CREMtau unaffected in the testis. CONCLUSION: Tamoxifen citrate reduced caput epididymal sperm chromatin compaction by reducing the testicular levels of proteins TP1, TP2 and P1 and the CREMtau involved in chromatin condensation during spermiogenesis. Tamoxifen citrate affects the expression of these genes at both the transcriptional and post-transcriptional levels.

Cyproterone acetate affects protamine gene expression in the testis of adult male rat.

The temporal effects of oral administration of cyproterone acetate (CPA), a progestational androgen receptor blocker, were studied on the fertility of adult male rat sires, at a dose of 20 mg kg-1 day-1 after 15 days of gavage. The treatment reduced the fertility and weights of accessory sex glands, without altering the serum levels of luteinizing hormone, follicle-stimulating hormone (FSH) and testosterone (T). Sperm counts were significantly reduced after treatment. Several changes were evident in caput epididymal sperm chromatin in treated rats. The in vitro decondensation rates of sperm chromatin and total fluorescent acridine orange (AO) dye uptake were enhanced. The fluorescent AO dye uptake by the double- and single-stranded sperm chromatin increased. The uptake of thiol-specific monobromobimane fluorescent dye by sperm chromatin was significantly reduced. Sperm of treated rats exhibited hypoprotamination. Protamine levels in the testis were significantly reduced after treatment. Androgen-binding protein (ABP) expression was significantly reduced in testis after treatment. A slight but significant increase was observed in cyclic AMP immunoexpression in testis after treatment. The expression and levels of transition proteins 1 (TP1) and 2 (TP2) as well as cyclic AMP response element modulator protein-tau were maintained at control levels in the testis of treated rats. The present study reports that androgen receptor occupation by CPA preferentially reduces the levels of spermatidal protamine in testis and spermatozoa involved in nuclear chromatin condensation. It is inferred that ABP could be mediating the effects of T in modulating the sequential expression of TPs and protamines during nuclear chromatin condensation. It is likely that indirect effects of T involve its aromatization in spermatids.