Iridoid glycoside Aucubin protects against nonylphenol-induced testicular damage in male rats via modulation of steroidogenic and apoptotic signaling.

Aucubin (AU) is one of the widespread compounds belonging to the group of iridoid glycosides, which possesses numerous beneficial properties. Nonylphenol (NP), is a synthetic environmental toxicant that has the potential to cause male infertility through excessive production of reactive oxygen species. In the current study, the remedial potential of Aucubin was assessed against NP-generated testicular damage in male rats. Animals were distributed into four groups and treated for 56 days in this study. Control-group (0.1% DMSO + food), NP group (100 µg/kg), NP + AU group (100 µg/kg + 5 mg/kg) and AU group (5 mg/kg). NP exposure significantly (p < 0.05) reduced the activity of antioxidant enzymes i.e., glutathione reductase, catalase (CAT), superoxide dismutase, glutathione peroxidase (GPx), and total protein content (TPC), whereas the level of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) was enhanced substantially (p < 0.05). Treatment with AU substantially (p < 0.05) recovered activities of antioxidant enzymes, TPC, ROS, and TBARS levels. Moreover, decrease in the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), plasma testosterone, sperm count, motility, sperm membrane integrity, and the number of spermatocytes of different stages along with the level of steroidogenic enzymes i.e., 17β-hydroxysteroid dehydrogenase (17β-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), and B-cell lymphoma 2 (Bcl-2) by NP administration were recovered to control values by AU treatment. However, AU mitigated the sperm abnormalities (head/midpiece/tail), the number of dead sperms, and proapoptotic proteins i.e., Bcl-2 associated X protein (Bax), caspase-9, and caspase-3 that were increased by NP. Besides, AU treatment recovered the NP-induced potential histopathological alterations in the testicular tissues such as the height of epithelium, seminiferous tubules diameter as well as the height of tunica propria. Overall, NP-induced toxicity was effectively recuperated by the AU administration. These results indicate that AU might be considered as a potential protective agent against testicular damage. The observed protection may be due to its antioxidant, anti-apoptotic, anti-inflammatory and androgenic potential.