Kanpalta, FatmaÖzbeyli, DilekSen, AliCevik, O. DağdevirenŞener, GökselErcan, FerihaEczacılık Meslek Bilimleri Bölümü2025-01-112025-01-11202141019-19411309-946910.5472/marumj.9889412-s2.0-105012388635https://doi.org/10.5472/marumj.988941Objective: Methotrexate (MTX) is a drug commonly used for the treatment of malign neoplastic and inflammatory diseases. Anti-oxidant and anti-inflammatory effects of bitter melon (BM) were reported. The aim of this study was to examine the effects of BM fruit extract on MTX-induced testicular and epididymal damage. Materials and Methods: Sprague Dawley male rats were divided into three groups (n=8) as control, MTX and MTX+BM. A single dose of MTX (20 mg/kg) was injected intraperitoneally to the MTX and MTX+BM groups. BM fruit extract (600 mg/kg) was applied to the MTX+BM group orally for 5 days. Testes were examined for general histopathology, proliferating and apoptotic cells. The epididymis samples were used for the evaluation of sperm morphology. Oxidative and inflammatory markers were analysed biochemically. Results: Increased abnormal spermatozoa, degenerated seminiferous tubules with increased apoptotic cells and decreased proliferative cells were observed in the MTX group. TNF-α, IL-1β, 8-hydroxy-2-deoxyguanosine and caspase-3 levels increased, superoxide dismutase and catalase levels decreased in both testis and epididymis samples. All these histological and biochemical parameters were ameliorated in the MTX+BM group. Conclusion: Methotrexate causes testis damage by decreasing spermatogenic cells and increasing apoptosis through oxidative stress and inflammation. BM extract improves testis and epididymis damage with its possible anti-oxidant and anti-inflammatory effects. © 2025 Elsevier B.V., All rights reserved.eninfo:eu-repo/semantics/openAccessBitter MelonEpididymisMethotrexateOxidative StressTestisArticle