Acrylamide-induced hypothalamic-pituitary-gonadal axis disruption in rats: Androgenic protective roles of apigenin by restoring testicular steroidogenesis through upregulation of 17β-HSD, CYP11A1 and CYP17A1

• Published in: Food and chemical toxicology 2024-12, Vol.194, p.115078, Article 115078
• Main Authors: Baraka, Sara M., Hussien, Yosra A., Ahmed-Farid, Omar A., Hassan, Azza, Saleh, Dalia O.
• Format: Article
• Language: English
• Subjects: 17-Hydroxysteroid Dehydrogenases - metabolism; 17β-HSD; Acrylamide; Acrylamide - toxicity; Androgens; Animals; Apigenin; Apigenin - pharmacology; Cholesterol Side-Chain Cleavage Enzyme - genetics; Cholesterol Side-Chain Cleavage Enzyme - metabolism; Hypothalamic-Pituitary-Gonadal Axis; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - metabolism; Male; Oxidative Stress - drug effects; Rats; Rats, Wistar; Steroid 17-alpha-Hydroxylase - genetics; Steroid 17-alpha-Hydroxylase - metabolism; Steroidogenesis; Testis; Testis - drug effects; Testis - metabolism; Testosterone - blood; Up-Regulation - drug effects
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2024.115078

Acrylamide (ARL) exposure induces significant toxicity to the hypothalamic-pituitary-gonadal (HPG) axis, leading to detrimental effects on behavior, neuroendocrine functions, steroidogensis, oxidative stress, inflammation, hormonal balance, sperm quality, and histopathological integrity in rats. This study investigates the protective role of oral apigenin (API; 10 or 20 mg/kg/day for 28 days) against ARL-induced toxicity in the HPG axis of male Wistar rats. Behavioral assessments revealed that ARL exposure impaired motor coordination and balance, as evidenced by increased landing foot splay distance and gait score. ARL-induced toxicity elevated brain Tau protein levels and disrupted hypothalamic GnRH levels, both mitigated by API. ARL triggered oxidative/nitrosative stress, reducing GSH contents and increasing MDA and NO levels in brain and testicular tissues, which were reversed by API. Hormonal imbalance, marked by decreased serum testosterone, FSH, and LH levels, was corrected by API. API enhanced semen quality parameters, with elevation in sperm count concentration and the percentages of both progressive motility and individual motility. It also normalized testicular PS and PC content, enhanced testicular cellular energy and restored seminal amino acid. The repression of testicular steroidogenesis-related enzymes CYP11A1, CYP17A1, and 17β-HSD following ARL exposure was alleviated by API administration. API also mitigated the inflammatory effects of ARL by reducing the expression of p–NF–κB p65 and TNF-α in testicular tissue. Histopathological examinations showed that API reduced neuronal and testicular degeneration, improving spermatogenesis. These findings suggest that API confers significant protective effects against ARL-induced HPG axis toxicity by restoring testicular steroidogenesis through the upregulation of 17β-HSD, CYP11A1, and CYP17A1, potentially due to its antioxidant, anti-inflammatory, and neuroprotective properties. •API mitigates acrylamide (ARL)-induced motor coordination and balance impairments in rats.•Treatment with API reduces brain Tau protein levels elevated by ARL toxicity.•API restores hypothalamic GnRH expression and serum testosterone, FSH, and LH levels.•Oxidative and nitrosative stress in brain and testicular tissues are alleviated by API with reduction in testicular inflammation markers.•API improves sperm quality parameters, including count, motility, viability, and morphology.