{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:52:28Z","timestamp":1785430348471,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Recep Tayyip Erdogan University Development Foundation","award":["02026003026210"],"award-info":[{"award-number":["02026003026210"]}]},{"award":["02026003026210"],"award-info":[{"award-number":["02026003026210"]}],"id":[{"id":"https:\/\/ror.org\/0468j1635","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Scientific Research Projects Unit of Recep Tayyip Erdogan University","award":["TLO-2025-1950"],"award-info":[{"award-number":["TLO-2025-1950"]}]},{"award":["TLO-2025-1950"],"award-info":[{"award-number":["TLO-2025-1950"]}],"id":[{"id":"https:\/\/ror.org\/0468j1635","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Scientific and Technological Research Council of T\u00fcrkiye","award":["1919B012312340"],"award-info":[{"award-number":["1919B012312340"]}]},{"award":["1919B012312340"],"award-info":[{"award-number":["1919B012312340"]}],"id":[{"id":"https:\/\/ror.org\/04w9kkr77","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Recep Tayyip Erdo\u011fan University","award":["02026004007243"],"award-info":[{"award-number":["02026004007243"]}]},{"award":["02026004007243"],"award-info":[{"award-number":["02026004007243"]}],"id":[{"id":"https:\/\/ror.org\/0468j1635","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Paclitaxel is a widely used chemotherapeutic agent whose clinical efficacy is limited by gonadotoxic side effects. Oxidative stress, apoptosis, and inflammation are key mechanisms underlying paclitaxel-induced testicular injury. This study aimed to comparatively evaluate the protective effects of melatonin and apigenin in a rat model. Methods: Adult male Sprague-Dawley rats were randomly assigned to seven groups: control, solvent control, melatonin, apigenin, paclitaxel, paclitaxel + melatonin, and paclitaxel + apigenin. Testicular malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured, together with apoptotic activity (caspase-3), oxidative DNA damage (8-OHdG), inflammatory signaling (NF-\u03baB\/p65, immunoreactivity), and histopathological alterations (Johnsen score). Results: Paclitaxel significantly increased MDA levels and decreased GSH content, accompanied by elevated caspase-3, 8-OHdG, and NF-\u03baB\/p65 immunoreactivity, as well as marked degeneration of seminiferous tubules. Melatonin improved redox balance, suppressed apoptotic and inflammatory responses, and preserved testicular architecture. Apigenin reduced lipid peroxidation and improved antioxidant status in paclitaxel-treated rats while decreasing GSH levels under basal conditions without inducing histological damage, suggesting a context-dependent redox-modulating effect. Both agents significantly improved Johnsen scores compared with paclitaxel alone. Conclusions: Paclitaxel-induced testicular injury is mediated by a coordinated interplay of oxidative stress, apoptosis, inflammation, and structural degeneration. Melatonin and apigenin effectively mitigate these processes, with apigenin exhibiting context-dependent antioxidant activity. These findings suggest that melatonin and apigenin may serve as adjunctive strategies for preserving male reproductive function during chemotherapy.<\/jats:p>","DOI":"10.3390\/nu18101643","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:02:27Z","timestamp":1779375747000},"page":"1643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Protective Effects of Melatonin and Apigenin Against Paclitaxel-Induced Testicular Injury in Rats: Oxidative Stress, DNA Damage, Apoptosis, and NF-\u03baB Signaling"],"prefix":"10.3390","volume":"18","author":[{"given":"Faruk","family":"Saydam","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Altuntoprak","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enes Bahadir","family":"Bay","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8506-1755","authenticated-orcid":false,"given":"Tolga","family":"Mercantepe","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4730-5015","authenticated-orcid":false,"given":"Atilla","family":"Topcu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7147-5087","authenticated-orcid":false,"given":"Sibel","family":"Mataraci Karakas","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","first-page":"139","article-title":"An Overview of Cancer Treatment Modalities","volume":"1","author":"Abbas","year":"2018","journal-title":"Neoplasm"},{"key":"ref_2","first-page":"e13394","article-title":"The role of propolis against paclitaxel-induced oligospermia, sperm abnormality, oxidative stress and DNA damage in testes of male rats","volume":"52","author":"Said","year":"2020","journal-title":"Andrologia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e11614","DOI":"10.1590\/1414-431x2021e11614","article-title":"The protective effect of melatonin supplementation against taxol-induced testicular cytotoxicity in adult rats","volume":"55","author":"Aboelwafa","year":"2022","journal-title":"Braz. 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