Reproductive and Hormonal Alterations Induced by Single and Combined Doses of Pregabalin and Baclofen Male Albino Rats: A Mechanistic Evaluation

Background and Objective: The prescription of pregabalin and baclofen is prevalent as drugs that act on the central nervous system. Excessive usage or off-label usage of these drugs is of great concern because of their potential effects on reproductive toxicity. This study was conducted to assess and compare the reproductive effects, hormonal effects, oxidative stress, and inflammatory response of pregabalin and baclofen in both single and combination treatments in male albino rats.
Methods: Rats were subjected to different protocols involving the use of pregabalin and baclofen singly and in combination in standard and double dosages. Measurements included sex hormone profile (testosterone, SSH [FSH], and ICSH [LH]) levels, antioxidant enzymes (superoxide dismutase [SOD], reduced glutathione [GSH], and catalase [CAT]), lipid peroxidation end-products (MDA and IsoPs), and inflammatory markers (TNF-α and NF-κB). Findings: The results revealed a dose-dependent disturbance in the HPG axis, which was reflected in the reduction in the concentrations of serum testosterone and gonadotropins. In addition, the medications caused acute oxidative stress, as reflected in the increase in the levels of MDA and IsoPs, together with the reduction in antioxidant capacity (SOD, GSH, and CAT). On the other hand, a significant increase in the levels of pro-inflammatory mediators (TNF-α and NF-κB) was observed, specifically in the groups exposed to double dose and combination therapy. Conclusions: Administration of high-dose pregabalin and baclofen, either alone or in combination, causes significant gonadotoxicity and endocrine disturbances in male rats. The mechanism of toxicity appears to be mainly through oxidative stress, inflammation, and HPG axis central suppression.