Highly active anti-retroviral therapy (HAART) is an effective anti-retroviral cocktail. Similarly, anti-Koch is highly potent against Mycobacterium tuberculosis. However, these drugs have been shown to impair male fertility. This study investigated the impact of HAART and anti-Koch, when used alone and co-administered, on testicular and sperm integrity. Thirty-two adult male Wistar rats were assigned randomly into four groups (n = 8), namely normal control, HAART-treated, anti-Koch-treated, and HAART + anti-Koch-treated. The doses of drugs were the human equivalent doses for rats. Administration was once daily per os and lasted for eight weeks. HAART aggravated anti-Koch-induced reduction in testicular and penile weights. In addition, anti-Koch also led to a distortion of testicular cytoarchitecture, disturbed spermatogenesis, and caused low sperm quality, including sperm dysmotility. More so, anti-Koch led to a significant elevation of uric acid and dysregulation of testicular lactate transport and glutathione content. These events were accompanied by enhanced lipid peroxidation and inflammation of the testicular tissue and reduced testicular and sperm DNA integrity. These adverse effects of anti-Koch were aggravated by co-administration of HAART. Thus, our results infer that HAART exacerbates anti-Koch-induced impairment of spermatogenesis and testicular and sperm toxicity through up-regulation of uric acid generation and dysregulation of lactate transport and glutathione system.
Copyright © 2021. Published by Elsevier Inc.