Oxidative and Inflammatory Disruptions of Hypothalamic-Pituitary-Testicular Axis by Octylphenol and Protective Role of Alpha Lipoic Acid: Histological and Biochemical Studies

Abstract

Objectives: Octylphenol (OP) is a member of the category of substances known as endocrine-disrupting chemicals and can interfere with the actions of steroid hormones, having negative implications on reproductive health. Alpha lipoic acid (αLA), a naturally occurring nutraceutical, has been shown to provide therapeutic benefits due to its antioxidant activity and capacity to reverse oxidative damage. Consequently, the current study is attending to estimate the protective effects of αLA against OP-induced male infertility. Methods: Forty male albino rats were randomly divided equally into four groups. Group I (control group) didnt received any materials, Group II (αLA-group) received alpha lipoic acid (40 mg/Kg/day), group III (OP-group) received octylphenol (50 mg/Kg/day), and group IV (protective group) received octylphenol (50 mg/Kg/day) plus alpha lipoic acid (40 mg/Kg/day) for 30 days. Serum reproductive hormones (gonadotropin releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, total oxidant status (TOS), and total antioxidant capacity (TAC) levels were measured. Histological and histochemical examinations of the hypothalamus, pituitary gland and testis, as well as immunohistochemical detection for tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the pituitary gland and testis were performed. Results: Rats of OP-group showed significant reduction of serum GnRH, FSH, LH, testosterone and TAC levels and significant rise of TOS levels. In parallel with these outcomes, several histopathological and histochemical abnormalities were observed in their hypothalamus, pituitary and testicular tissues. Additionally these structural abnormalities were associated with increased TNF-α and IL-6 expressions in both pituitary and testicular tissues. On other hand, rats of protective group showed enormous improvements in biochemical, histopathological, and immunohistochemical derangements induced by OP. Insignificant differences in the biochemical, histopathological, and immunohistochemical examinations were observed between control group and αLA-group. Conclusions: Short-term exposure of OP at low doses disturbs the hypothalamic-pituitary-gonadal (HPG) axis associated with increased oxidative stress, inflammation and structural abnormalities with successful reversion of theses derangements by αLA via its antioxidant and anti-inflammatory properties.