Abstract
Reproductive toxicity is a major challenge associated with aluminum (Al) exposure. Therefore, this study aimed to investigate the effects of zinc oxide nanoparticle (ZnONP) treatment on Al-induced reproductive toxicity in rats. Thirty-two adult male albino rats were allocated into four equal groups as follows: control, AlCl3 orally administered group (100 mg/kg bwt), ZnONPs injected intraperitoneally (i.p.) group (4 mg/kg bwt), and ZnONPs + AlCl3-treated group. The treatment was daily extended for 42 consecutive days. Oral administration of AlCl3 showed an oxidative damage confirmed by an increase in malondialdehyde and nitric oxide levels and superoxide dismutase activity and accompanied by a decrease in glutathione content and catalase activity. Also, AlCl3 administration increased the pro-inflammatory mediator tumor necrosis factor-alpha. Furthermore, significant declines in the levels of serum male reproductive hormones testosterone, luteinizing hormone, and follicle-stimulating hormone in AlCl3-intoxicated rats were noticed. In parallel, severe histopathological alterations were observed in testis tissues. Additionally, the immunohistochemical analysis showed that AlCl3 administration potentiates cell death in the testicular tissue by elevating the immunostaining intensity signal for the pro-apoptotic protein, cysteinyl aspartate specific protease-3 (caspase-3) and a marked depletion in the cell proliferation expression marker, Ki-67, in germinal cells of AlCl3-treated group. On the other hand, the daily i.p. injection to rats with ZnONPs before AlCl3 was found to ameliorate the reproductive toxicity induced by Al administration through reducing the testicular oxidative stress and improving the inflammatory, apoptotic, and reproductive markers as well as histopathological alterations in the testis. These results suggest that ZnONPs could be used as an alternative agent to minimize the reproductive toxicity associated with Al exposure through its antioxidant, anti-inflammatory, anti-apoptotic, and reproductive modulatory activities.