Does ramelteon have an ameliorative effect in MTX-induced testicular injury?

Abstract

Aims: The aim of this study was to investigate the potential protective effect of Ramelteon (RMT), which exhibits antioxidant, anti-inflammatory and antiapoptotic properties, against testicular damage induced by Methotrexate (MTX), which is widely used in the treatment of various diseases, including chemotherapy. Methods: 32 Wistar albino rats were equally divided into four groups: Control (group I), MTX (group II), MTX+RMT (group III) and RMT (group IV). Histologic evaluation was performed using Hematoxylin and Eosin (H&E) staining, immunohistochemical analysis using TNF-alpha and Cas-3, and biochemical evaluation using TAS, TOS and OSI. Results: Histologic analysis using H&E staining revealed a significant difference between group I and groups II and III (p<0.05), while no significant difference was observed between group IV and the other groups (p>0.05). While normal histologic structures were observed in groups I and IV, histopathologic findings were noted in groups II and III. Immunohistochemical evaluation of TNF-alpha and Cas-3 showed a significant difference between group I and groups II and III (p<0.05), while no significant difference was observed between group IV and other groups (p>0.05). The highest immunostaining intensity was observed in group II. Biochemical evaluation revealed statistically significant differences in TAS, TOS and OSI parameters reflecting oxidative stress differences between the groups (p<0.05). Conclusion: Anti-inflammatory, antioxidant and antiapoptotic properties of RMT demonstrated its protective effect against MTX-induced testicular injury in rats. Histological, immunohistochemical and biochemical analyses underline the potential role of RMT as a protective agent in MTX-induced testicular injury. This research aims to contribute to the understanding of potential applications to reduce the adverse effects of MTX therapy on reproductive health.