<p>Aim: The toxic effects of methotrexate, a chemotherapeutic, on</p><p>the testicles is an important side effect. Methotrexate impairs</p><p>spermatogenesis and fertility and causes oligospermia. In this</p><p>study, we aimed to minimize the testicular toxicity, those being</p><p>the side effects of methotrexate, by using the probable protective</p><p>effects of α-lipoic acid, a potent antioxidant.</p><p>Material and Method: Twenty-eight male Sprague Dawley rats</p><p>that we employed in this research were separated into three groups</p><p>as control (0.09% PS) (n=8), methotrexate (20 mg/kg) (n= 10), and</p><p>methotrexate (20 mg/kg) + α-lipoic acid (100 mg/kg) (n= 10). We</p><p>performed a histochemical analysis on the testicular tissue of rats</p><p>using hematoxylin-eosin and Masson’s trichrome. We performed</p><p>an immunohistochemical analysis using inducible nitric oxide</p><p>synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) primer ab.</p><p>Results: The histochemical evaluation revealed a significant</p><p>decrease in the methotrexate-induced testicular toxicity in the</p><p>α-lipoic acid-treated groups. On the other hand, TNF-α and iNOS</p><p>immunostaining results were also observed to support these</p><p>results.</p><p>Conclusion: The treatment use of α-lipoic acid succeeded in</p><p>protecting against methotrexate-induced testicular damage</p><p>through an α-lipoic acid-mediated antioxidant and antiinflammatory</p><p>mechanisms. α-lipoic acid can be used in</p><p>combination with methotrexate as a protector against side effects</p><p>during anticancer therapy. In the present study, it was shown that</p><p>α-lipoic acid can be used in combination with methotrexate as a</p><p>protector against side effects during anticancer treatment.</p><p>Keywords: Alpha-lipoic acid, anti-inflammatory, methotrexate,</p><p>testicular damage, oxidative stress</p>