Chronic exposure to mining-contaminated borehole water impairs the entire male reproductive axis: partial mitigation by alpha-lipoic acid in Wistar rats.

Introduction: Mining activities, industrial discharges, and poor waste management in many developing countries, including Nigeria, have led to widespread contamination of groundwater with mixtures of heavy metals such as lead, cadmium, arsenic, and mercury. In mining-impacted regions of Ebonyi State, borehole water, the primary drinking source for rural communities regularly exceeds WHO permissible limits, resulting in chronic low-dose exposure that threatens male reproductive health through disruption of the entire hypothalamus-pituitary-gonadal (HPG) axis. This study investigated the reproductive toxicity of naturally contaminated borehole water and evaluated the protective and therapeutic potential of alpha-lipoic acid (ALA) in adult male Wistar rats. Methodology: Thirty adult male Wistar rats were divided into five groups (n = 5): normal control, heavy metal-contaminated water only (28 days), ALA only (25 mg/kg), post-treatment (contaminated water 28 days followed by ALA 14 days), and pre-treatment (ALA 14 days followed by contaminated water 28 days). Water from a mining area in Ebonyi State, Nigeria, contained Pb (2.4 mg/L), Cd (1.7 mg/L), As (1.2 mg/L), and Hg (0.8 mg/L), exceeding WHO limits. After sacrifice, serum hormones (GnRH, FSH, LH, testosterone), antioxidant status, inflammatory markers, sperm parameters, steroidogenic enzymes, and histopathology of the hypothalamus, pituitary, and testes were assessed. Results: Contaminated water significantly reduced body weight, organ weights, sperm quality, GnRH, FSH, testosterone, antioxidant enzymes, and steroidogenic protein expression while increasing inflammation and histopathological damage across the HPG axis. Post-treatment with ALA significantly improved most parameters compared to the heavy metal-only group, whereas pre-treatment offered limited protection. However, neither regimen fully restored values to control levels. Conclusion: Chronic exposure to naturally heavy metal-contaminated drinking water induces profound multi-level HPG axis dysfunction. Alpha-lipoic acid at 25 mg/kg provides significant but incomplete protection, with post-exposure administration being more effective. These findings highlight the need for higher doses or combination therapies and underscore the urgent public health risk in affected regions.