Ethanol exacerbates manganese – induced functional alterations along the hypothalamic-pituitary-gonadal axis of male rats

•Ethanol exacerbated manganese – induced oxidative stress and inflammation along the hypothalamic – pituitary – gonadal axis•Ethanol exacerbated manganese – induced diminution in reproductive hormones and marker enzymes of testicular functions.•Ethanol exacerbates manganese – induced functional alteration along the hypothalamic – pituitary – gonadal axis rats. Manganese (Mn) exposure has been reported to induce reproductive dysfunction in animal and humans. Studies have shown that a large percentage of adolescent and adult populations tend to consume alcohol in a binge pattern. However, there is no information on the influence of alcohol on Mn – induced functional alteration along the hypothalamic – pituitary – gonadal axis. This study aimed to evaluate the influence of ethanol (EtOH) on Mn – induced functional alteration along the hypothalamic – pituitary – gonadal axis. Rats were exposed to Mn alone at 30 mg/kg body weight or co-expose with EtOH at 1.25 and 5 g/kg body weight for 35 consecutive days. Results showed that EtOH exposure significantly (p ≤ 0.05) exacerbated Mn – induced decrease in antioxidant enzymes activities, glutathione level and increased oxidative stress biomarkers in the hypothalamus, testes an epididymis of the exposed rats. Moreover, induction of inflammation was associated with disruption of histo-architecture of the hypothalamus, testes and epididymis of rats treated with Mn alone, EtOH alone or in combination. Furthermore, EtOH significantly exacerbated Mn – induced diminution in reproductive hormones and marker enzymes of testicular functions coupled with decreased sperm quantity and quality. Taken together, EtOH exacerbates Mn – induced functional alteration along the hypothalamic – pituitary – gonadal axis in rats via mechanisms involving induction of oxidative/nitrosative stress, lipid peroxidation and inflammation in rats.