Abstract
Roflumilast (ROF) (3-cyclo-propylmethoxy-4-difuorome-thoxy-N-[3,5-di-chloropyrid-4-yl] benzamide) is a second generation and forcible phosphodiesterase-4 (PDE4) inhibitor. This study aims to investigate the effects of chronic Roflumilast in different doses on testicular tissue and testosterone levels in healthy Sprague-Dawley rats. During the research, the 6 weeks old (180–200 gr), 36 male rats were divided into 4 groups. Roflumilast (ROF) was administered as 0.5 mg/kg and 1 mg/kg by oral gavage for four weeks, once each day. Hematoxylin-Eosin (H&E) staining for histopathological examinations in testicular tissue, immunohistochemical and immunofluorescence examinations for Caspase-3, Apoptosis Inducing Factor (AIF) and Light Chain 3β (LC3B) expression levels, and ELISA method used to determine serum testosterone levels. Data were analyzed using SPSS v.22 with Kruskal-Wallis, Mann Whitney-U, and Wilcoxon tests. Roflumilast group lost weight compared to the control and sham. Shedding in the seminiferous epithelium, degenerations in the interstitial area, separation between cells, desquamation, interstitial edema and degenerative changes in the testicular tissue was observed. While apoptosis and autophagy determined by Caspase-3, AIF and LC3B were close and statistically insignificant in control and sham, there was significantly increased apoptotic and autophagic changes and immunopositivity in the ROF groups. The 1 mg/kg Roflumilast group’s serum testosterone level was lower than control, sham and 0.5 mg/kg Roflumilast groups. When the research data was evaluated, it was determined that the chronic use of the active ingredient Roflumilast, which has a broad-spectrum area such as COPD, arthritis, neurodegenerative diseases, liver and dermatology, had negative effects on the testicular tissue and testosterone level of rats.