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    Evaluation of caffeic acid fenethyl ester in testicular damage caused by fluoxetine hydrochloride in rats: effects of fluoxetine hydrochloride on testes
    (Springer, 2025) Asoglu, Zehra Demiray; Balli, Ebru; Bayrak, Gulsen; Yalin, Serap; Ozturk, Ayla Batu; Kaya, Merih Akkapulu; Sengul, Merve Turkegun
    In our study, the aim was to investigate the protective effect of caffeic acid phenethyl ester, which has a wide spectrum of activity, against testicular damage caused by fluoxetine hydrochloride. In our study, 25 male Wistar Albino rats were used, and the rats were divided into five groups with an equal number of rats in each group: control 1 (saline), control 2 (dimethyl sulfoxide-DMSO), fluoxetine group (FLX), caffeic acid phenethyl ester group (CAPE), and fluoxetine + caffeic acid phenethyl ester group (FLX + CAPE). After a 4-week experiment, blood samples were collected, and testicular tissues were excised. For light microscopic evaluation, hematoxylin-eosin (H&E) and toluidine blue (TB) staining were performed. Immunohistochemical examinations were carried out with caspase-3, Bcl-2, and PCNA immunostaining. As a result of statistical evaluation of the morphologic and immunohistochemical examinations, it was determined tubule diameter (p < 0.001, eta(2) = 0.798), germinal epithelium thickness (p = 0.0001, eta(2) = 0.573), and Johnsen score (p < 0.001, eta(2) = 0.928) decreased in the FLX group compared to all groups, while these valuesincreased in the FLX + CAPE group compared to the FLX group. Similarly, body weight and right testicular weight too. Caspase-3 expression in Leydig cells and Bcl-2 expression in seminiferous tubules were increased in FLX group compared to SF, DMSO, and CAPE groups, while they were decreased in FLX + CAPE group compared to FLX group. PCNA index was decreased in FLX group compared to SF, DMSO, and CAPE groups, while it was increased in FLX + CAPE group compared to FLX group. In biochemical analyses, MDA level was increased in the FLX group, while this value was decreased in the FLX + CAPE group. No apparent change was observed in SOD and CAT levels. Our findings showed that FLX induced apoptosis by causing structural damage in the testis through oxidative effects, while CAPE, with its antioxidant effect, repaired this damage, reducing lipid peroxidation and oxidative stress.