{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:58:02Z","timestamp":1785452282776,"version":"3.56.0"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007102","name":"Zagazig University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007102","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Doxorubicin (DOX) is a commonly prescribed\u00a0chemotherapeutic\u00a0agent whose clinical application is limited by its toxicity to rapidly dividing organs, particularly the testes.This study explored the protective potential of ferulic acid-loaded niosomes (FA-NIO) against DOX-induced testicular dysfunction in rats and elucidated the underlying molecular mechanisms. Forty male rats were allocated into four groups: Group 1 was given saline, Group 2 was given DOX, Group 3 was given DOX\u2009+\u2009free FA, and Group 4 was given DOX\u2009+\u2009FA-NIO. Serum reproductive hormone levels, testicular oxidative stress indices, and the expression of genes and proteins relevant to NLRP3 inflammasome signaling, apoptosis (Bax and Bcl-2), and steroidogenesis (StAR, CYP11A1, and 3\u03b2-HSD) were assessed, along with histopathological changes in the testicular tissue. DOX administration significantly increased MDA (malondialdehyde) while suppressing antioxidant defences, accompanied by hormonal imbalance, severe histopathological damage, upregulation of Bax, NLRP3, and IL-1\u03b2, downregulation of Bcl-2, and inhibition of steroidogenic gene expression. On the other hand, these changes were partially mitigated in the DOX\u2009+\u2009free FA group. Notably, FA-NIO treatment reduced histopathological damage, normalised reproductive hormone levels, markedly increased steroidogenesis-related gene expression, suppressed apoptotic and inflammasome-related gene expression, and greatly restored antioxidant capacity. Compared with DOX\u2009+\u2009free FA, FA-NIO consistently demonstrated greater protective efficacy. In summary, FA-NIO targets oxidative stress-mediated apoptosis, attenuates NLRP3 inflammasome-related signaling, and restores steroidogenic function, thereby successfully attenuating DOX-induced testicular toxicity. These results suggest that FA-NIO may represent a promising nanotherapeutic strategy for attenuating chemotherapy-induced reproductive toxicity in a rat model.<\/jats:p>","DOI":"10.1186\/s40659-026-00707-9","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:33:49Z","timestamp":1785162829000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting oxidative stress-NLRP3-apoptotic-steroidogenic axis in doxorubicin-induced testicular toxicity: protective efficacy of ferulic acid niosomes"],"prefix":"10.1186","volume":"59","author":[{"given":"Mahran Mohamed Abd","family":"El-Emam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya Elhady","family":"Atia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona A.","family":"Bakry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabab A.","family":"Husseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Elrefaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha Osama","family":"El-Shaer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safaa I.","family":"Khater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed El-Sayed","family":"Yousef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein I.","family":"Elbelbesy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"12","key":"707_CR1","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.3390\/ANTIOX12081487","volume":"2023","author":"MM Abd El-Emam","year":"2023","unstructured":"Abd El-Emam MM, Mostafa M, Farag AA, Youssef HS, El-Demerdash AS, Bayoumi H, et al. The potential effects of quercetin-loaded nanoliposomes on amoxicillin\/clavulanate-induced hepatic damage: targeting the SIRT1\/Nrf2\/NF-\u03baB Signaling pathway and microbiota modulation. Antioxidants. 2023;2023(12):1487. https:\/\/doi.org\/10.3390\/ANTIOX12081487.","journal-title":"Antioxidants"},{"key":"707_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/J.TOXREP.2024.101869","volume":"14","author":"RM Abdel-Megeed","year":"2025","unstructured":"Abdel-Megeed RM, Abdel-Hamid AHZ, Kadry MO. Titanium nanostructure mitigating doxorubicin\u2013induced testicular toxicity in rats via regulating major autophagy signaling pathways. Toxicol Rep. 2025;14:101869. https:\/\/doi.org\/10.1016\/J.TOXREP.2024.101869.","journal-title":"Toxicol Rep"},{"key":"707_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/J.PRMCM.2023.100257","volume":"7","author":"OE Adeyi","year":"2023","unstructured":"Adeyi OE, Somade OT, James AS, Adeyi AO, Ogbonna-Eze SN, Salako OQ, et al. Ferulic acid mitigates 2-methoxyethanol-induced testicular oxidative stress via combined downregulation of FoxO1, PTEN, and modulation of Nrf2-Hmox1-NQO1 signaling pathway in rats. Pharmacol Res Mod Chin M\u00ed. 2023;7:100257. https:\/\/doi.org\/10.1016\/J.PRMCM.2023.100257.","journal-title":"Pharmacol Res Mod Chin M\u00ed"},{"key":"707_CR4","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","volume":"105","author":"H Aebi","year":"1984","unstructured":"Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121\u20136. https:\/\/doi.org\/10.1016\/S0076-6879(84)05016-3.","journal-title":"Methods Enzymol"},{"key":"707_CR5","doi-asserted-by":"publisher","unstructured":"Afolabi, O.K., Wusu, A.D., Ugbaja, R., Fatoki, J.O., 2018. Aluminium phosphide-induced testicular toxicity through oxidative stress in Wistar rats: Ameliorative role of hesperidin. Toxicology Research and Application 2. https:\/\/doi.org\/10.1177\/2397847318812794","DOI":"10.1177\/2397847318812794"},{"key":"707_CR6","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/S43188-024-00270-Z","volume":"41","author":"K A\u011fan","year":"2025","unstructured":"A\u011fan K, Kaya ST, A\u011fan AF, A\u011fyar-Yolda\u015f P, Yolda\u015f T, \u0130kinci-Kele\u015f A, et al. Alleviating doxorubicin-induced reproductive toxicity: protective and androgenic effects of drone larvae on sperm morphology and hormonal balance. Toxicol Res. 2025;41:149\u201365. https:\/\/doi.org\/10.1007\/S43188-024-00270-Z.","journal-title":"Toxicol Res"},{"key":"707_CR7","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","volume":"397","author":"A Agarwal","year":"2021","unstructured":"Agarwal A, Baskaran S, Parekh N, Cho CL, Henkel R, Vij S, et al. Male infertility. Lancet. 2021;397:319\u201333. https:\/\/doi.org\/10.1016\/S0140-6736(20)32667-2.","journal-title":"Lancet"},{"key":"707_CR8","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1007\/978-0-387-09597-4_9","volume-title":"Molecular mechanisms in spermatogenesis","author":"RJ Aitken","year":"2009","unstructured":"Aitken RJ. Antioxidant systems and oxidative stress in the testes. In: Molecular mechanisms in spermatogenesis. 2009. p. 154\u201371."},{"key":"707_CR9","doi-asserted-by":"publisher","unstructured":"Aksu, E.H., Kandemir, F.M., Y\u0131ld\u0131r\u0131m, S., K\u00fc\u00e7\u00fckler, S., D\u00f6rtbudak, M.B., \u00c7a\u011flayan, C., Benzer, F., 2019. Palliative effect of curcumin on doxorubicin-induced testicular damage in male rats. J Biochem Mol Toxicol 33. https:\/\/doi.org\/10.1002\/JBT.22384","DOI":"10.1002\/JBT.22384"},{"key":"707_CR10","doi-asserted-by":"crossref","unstructured":"Aldawsari MF, Moglad EH, Alotaibi HF, Alkahtani HM, Khafagy ES. 2023. Ophthalmic Bimatoprost-Loaded Niosomal In Situ Gel: Preparation, Optimization, and In Vivo Pharmacodynamics Study. Polymers (Basel). 15.","DOI":"10.3390\/polym15214336"},{"key":"707_CR11","doi-asserted-by":"publisher","first-page":"4960","DOI":"10.3390\/MA18214960\/S1","volume":"18","author":"A Antonelli","year":"2025","unstructured":"Antonelli A, Palma F. Nanocarrier-Based Delivery Systems for Natural Compounds Across Research Stages. Materials. 2025;18:4960. https:\/\/doi.org\/10.3390\/MA18214960\/S1.","journal-title":"Materials"},{"key":"707_CR12","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.3390\/ijms22031319","volume":"22","author":"P Antonuccio","year":"2021","unstructured":"Antonuccio P, Micali AG, Romeo C, Freni J, Vermiglio G, Puzzolo D, et al. NLRP3 Inflammasome: A New Pharmacological Target for Reducing Testicular Damage Associated with Varicocele. IJMS. 2021;22:1319. https:\/\/doi.org\/10.3390\/ijms22031319.","journal-title":"IJMS"},{"key":"707_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/J.TOXREP.2024.101827","volume":"13","author":"EE Asanga","year":"2024","unstructured":"Asanga EE, Okokon JE, Joseph AP, Ekeleme CM, Ilechukwu SB, Anagboso MO, et al. The attenuation of doxorubicin-induced testicular toxicity with improved testicular histoarchitecture of mice by the bioactive compounds in Solanum anomalum leaves: Experimental and computational studies. Toxicol Rep. 2024;13:101827. https:\/\/doi.org\/10.1016\/J.TOXREP.2024.101827.","journal-title":"Toxicol Rep"},{"key":"707_CR14","doi-asserted-by":"publisher","unstructured":"Husseini RA, Emam SE, Abd El Razek AM, Hamed E, Elshamy AI, Abdelnabi DM. Assessment of the therapeutic efficacy of rutin-loaded PLGA nanocapsule-based gel against imiquimod-induced psoriasis model using box-behnken design for optimization. Int J Pharm. 2026;689:126458. Epub 2025 Dec 11. PMID: 41386359. https:\/\/doi.org\/10.1016\/j.ijpharm.2025.126458","DOI":"10.1016\/j.ijpharm.2025.126458"},{"key":"707_CR15","unstructured":"Bancroft, J., Layton, C., 2013. The Hematoxylin and Eosin. In: Suvarna, S.K., Layton, C. and Bancroft, J.D., Eds.,. Theory and Practice of histological techniques, 7th Edition, Churchill Livingstone of El Sevier, Philadelphia, Ch. 10 and 11 179\u2013220."},{"issue":"8","key":"707_CR16","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/nrurol.2017.69","volume":"14","author":"S Bisht","year":"2017","unstructured":"Bisht S, Faiq M, Tolahunase M, Dada R. Oxidative stress and male infertility. Nat Rev Urol. 2017;14(8):470\u201385. https:\/\/doi.org\/10.1038\/nrurol.2017.69.","journal-title":"Nat Rev Urol"},{"key":"707_CR17","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/J.FERTNSTERT.2021.12.012","volume":"117","author":"L Bj\u00f6rndahl","year":"2022","unstructured":"Bj\u00f6rndahl L, Kirkman Brown J. The sixth edition of the WHO laboratory manual for the examination and processing of human semen: ensuring quality and standardization in basic examination of human ejaculates. Fertil Steril. 2022;117:246\u201351. https:\/\/doi.org\/10.1016\/J.FERTNSTERT.2021.12.012.","journal-title":"Fertil Steril"},{"key":"707_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/S41467-024-46190-2","author":"A Chi","year":"2024","unstructured":"Chi A, Yang B, Dai H, Li X, Mo J, Gao Y, et al. Stem Leydig cells support macrophage immunological homeostasis through mitochondrial transfer in mice. Nat Commun. 2024. https:\/\/doi.org\/10.1038\/S41467-024-46190-2.","journal-title":"Nat Commun"},{"key":"707_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/J.BIOPHA.2021.112004","volume":"142","author":"A Das","year":"2021","unstructured":"Das A, Baidya R, Chakraborty T, Samanta AK, Roy S. Pharmacological basis and new insights of taxifolin: a comprehensive review. Biomed Pharmacother. 2021;142:112004. https:\/\/doi.org\/10.1016\/J.BIOPHA.2021.112004.","journal-title":"Biomed Pharmacother"},{"key":"707_CR20","doi-asserted-by":"publisher","unstructured":"Das S, Wong ABH. Stabilization of ferulic acid in topical gel formulation via nanoencapsulation and pH optimization. Sci Rep. 2020;10:12288. . https:\/\/doi.org\/10.1038\/s41598-020-68732-6","DOI":"10.1038\/s41598-020-68732-6"},{"key":"707_CR21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/J.UROLOGY.2022.06.036","volume":"169","author":"P Diaz","year":"2022","unstructured":"Diaz P, Dullea A, Chu KY, Zizzo J, Loloi J, Reddy R, et al. Future of male infertility evaluation and treatment: brief review of emerging technology. Urology. 2022;169:9\u201316. https:\/\/doi.org\/10.1016\/J.UROLOGY.2022.06.036.","journal-title":"Urology"},{"key":"707_CR22","doi-asserted-by":"publisher","DOI":"10.3390\/cells14231906","volume":"14","author":"HM Elhessy","year":"2025","unstructured":"Elhessy HM, Khattab BA, Badawy AM, Elsayed HRH, Alghamdi MA, Zafrah H, et al. Thymoquinone attenuates aluminum chloride-induced testicular injury by inhibiting NLRP3\/Caspase 1\/IL-1\u03b2 inflammasome signaling and polarizing the macrophages toward anti-inflammatory M2 phenotype. Cells. 2025;14:1906. https:\/\/doi.org\/10.3390\/cells14231906.","journal-title":"Cells"},{"key":"707_CR23","doi-asserted-by":"publisher","unstructured":"Essa, H.A., Ali, E., Zahraa Abd EL Hakam, F. El, Akl, E.M., 2025. Nano-encapsulated ferulic acid in sesame protein isolate alleviates acrylamide-induced liver toxicity and genotoxicity in rats via oxidative stress and DNA damage modulation. BMC Pharmacology and Toxicology 26, 120-. https:\/\/doi.org\/10.1186\/S40360-025-00946-8\/FIGURES\/9","DOI":"10.1186\/S40360-025-00946-8\/FIGURES\/9"},{"key":"707_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/ph18111625","volume":"18","author":"ES Gad","year":"2025","unstructured":"Gad ES, Gad. Hepatoprotection by methylene blue against doxorubicin toxicity through coordinated modulation of oxidative stress, ER stress, and apoptotic pathways. Pharmaceuticals. 2025;18:1625. https:\/\/doi.org\/10.3390\/ph18111625.","journal-title":"Pharmaceuticals"},{"key":"707_CR25","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1177\/0300985813485099","volume":"50","author":"KN Gibson-Corley","year":"2013","unstructured":"Gibson-Corley KN, Olivier AK, Meyerholz DK. Principles for Valid Histopathologic Scoring in Research. Vet Pathol. 2013;50:1007\u201315. https:\/\/doi.org\/10.1177\/0300985813485099.","journal-title":"Vet Pathol"},{"key":"707_CR26","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1177\/0960327119862006","volume":"38","author":"C Gurel","year":"2019","unstructured":"Gurel C, Kuscu GC, Buhur A, Dagdeviren M, Oltulu F, Karabay Yavasoglu NU, et al. Fluvastatin attenuates doxorubicin-induced testicular toxicity in rats by reducing oxidative stress and regulating the blood-testis barrier via mTOR signaling pathway. Hum Exp Toxicol. 2019;38:1329\u201343. https:\/\/doi.org\/10.1177\/0960327119862006.","journal-title":"Hum Exp Toxicol"},{"key":"707_CR27","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1177\/29.4.6166661","volume":"29","author":"SM Hsu","year":"1981","unstructured":"Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981;29:577\u201380. https:\/\/doi.org\/10.1177\/29.4.6166661.","journal-title":"J Histochem Cytochem"},{"key":"707_CR28","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1186\/S12951-024-02789-7\/FIGURES\/9","volume":"22","author":"C Huang","year":"2024","unstructured":"Huang C, Huangfu C, Bai Z, Zhu L, Shen P, Wang N, et al. Multifunctional carbomer based ferulic acid hydrogel promotes wound healing in radiation-induced skin injury by inactivating NLRP3 inflammasome. J Nanobiotechnol. 2024;22:576. https:\/\/doi.org\/10.1186\/S12951-024-02789-7\/FIGURES\/9.","journal-title":"J Nanobiotechnol"},{"issue":"87","key":"707_CR29","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/0167-4838(87)90309-8","volume":"4838","author":"KR Huber","year":"1987","unstructured":"Huber KR, Sridhar R, Griffith EH, Amma EL, Roberts J. Superoxide dismutase-like activities of copper(II) complexes tested in serum. Biochimica et Biophysica Acta (BBA). 1987;4838(87):267\u201376. https:\/\/doi.org\/10.1016\/0167-4838(87)90309-8.","journal-title":"Biochimica et Biophysica Acta (BBA)"},{"key":"707_CR30","doi-asserted-by":"publisher","first-page":"107225","DOI":"10.1016\/j.jddst.2025.107225","volume":"112","author":"RA Husseini","year":"2025","unstructured":"Husseini RA, Abd El-Emam MM, Emam SE, Hamed E, Elshamy AI, Abdelnabi DM. Rutin-loaded fast-dissolving sublingual niosomal film: Design, characterization, hepatoprotective potential, and pharmacokinetic evaluation in ceftriaxone-induced liver injury in rats. J Drug Deliv Sci Technol. 2025;112:107225. . https:\/\/doi.org\/10.1016\/j.jddst.2025.107225","journal-title":"J Drug Deliv Sci Technol"},{"key":"707_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/S12247-025-10026-3\/FIGURES\/8","volume":"20","author":"M Ibrahim","year":"2025","unstructured":"Ibrahim M, Mansour MF, Abd El-Emam MM, Khamis T, Kilany MS, Alsemeh AE, et al. Rutin-Loaded Nanocapsules Mitigate Vancomycin-Induced Hepatotoxicity: Development, Characterization, Optimization, and In Vivo Evaluation. J Pharm Innov. 2025;20:1\u201319. https:\/\/doi.org\/10.1007\/S12247-025-10026-3\/FIGURES\/8.","journal-title":"J Pharm Innov"},{"key":"707_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/J.TAAP.2023.116657","author":"I Ishtiaq","year":"2023","unstructured":"Ishtiaq I, Zeb A, Badshah H, Alattar A, Alshaman R, Koh PO, et al. Enhanced cardioprotective activity of ferulic acid-loaded solid lipid nanoparticle in an animal model of myocardial injury. Toxicol Appl Pharmacol. 2023. https:\/\/doi.org\/10.1016\/J.TAAP.2023.116657.","journal-title":"Toxicol Appl Pharmacol"},{"issue":"2","key":"707_CR33","first-page":"159","volume":"3","author":"AS Jalali","year":"2013","unstructured":"Jalali AS, Hasanzadeh S. Crataegus monogyna fruit aqueous extract as a protective agent against doxorubicin-induced reproductive toxicity in male rats. Avicenna journal of phytomedicine. 2013;3(2):159.","journal-title":"Avicenna journal of phytomedicine"},{"key":"707_CR34","doi-asserted-by":"publisher","DOI":"10.1186\/S12906-019-2617-2","author":"N Jaradat","year":"2019","unstructured":"Jaradat N, Zaid AN. Herbal remedies used for the treatment of infertility in males and females by traditional healers in the rural areas of the West Bank\/Palestine. BMC Complement Altern Med. 2019. https:\/\/doi.org\/10.1186\/S12906-019-2617-2.","journal-title":"BMC Complement Altern Med"},{"key":"707_CR35","doi-asserted-by":"publisher","first-page":"154439","DOI":"10.1016\/j.phymed.2022.154439","volume":"106","author":"Q Jiang","year":"2022","unstructured":"Jiang Q, Chen X, Tian X, Zhang J, Xue S, Jiang Y, et al. Tanshinone I inhibits doxorubicin-induced cardiotoxicity by regulating Nrf2 signaling pathway. Phytomedicine. 2022;106:154439.","journal-title":"Phytomedicine"},{"issue":"22","key":"707_CR36","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.3390\/MOLECULES22101589","volume":"2017","author":"R Johnson","year":"2017","unstructured":"Johnson R, Shabalala S, Louw J, Kappo AP, Muller CJF. Aspalathin reverts doxorubicin-induced cardiotoxicity through increased autophagy and decreased expression of p53\/mTOR\/p62 signaling. Molecules. 2017;2017(22):1589. https:\/\/doi.org\/10.3390\/MOLECULES22101589.","journal-title":"Molecules"},{"key":"707_CR37","doi-asserted-by":"publisher","DOI":"10.1111\/JFBC.13505","author":"RB Kassab","year":"2020","unstructured":"Kassab RB, Lokman MS, Daabo HMA, Gaber DA, Habotta OA, Hafez MM, et al. Ferulic acid influences Nrf2 activation to restore testicular tissue from cadmium-induced oxidative challenge, inflammation, and apoptosis in rats. J Food Biochem. 2020. https:\/\/doi.org\/10.1111\/JFBC.13505.","journal-title":"J Food Biochem"},{"key":"707_CR38","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1080\/01926230290105721","volume":"30","author":"JR Latendresse","year":"2002","unstructured":"Latendresse JR, Warbrittion AR, Jonassen H, Creasy DM. Fixation of testes and eyes using a modified Davidson\u2019s fluid: comparison with Bouin\u2019s fluid and conventional Davidson\u2019s fluid. Toxicol Pathol. 2002;30:524\u201333. https:\/\/doi.org\/10.1080\/01926230290105721.","journal-title":"Toxicol Pathol"},{"issue":"12","key":"707_CR39","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1038\/s41598-022-06229-0","volume":"2022","author":"Z Li","year":"2022","unstructured":"Li Z, Hu J, Bao C, Gao C, Zhang N, Cardona CJ, et al. Activation of the NLRP3 inflammasome and elevation of interleukin-1\u03b2 secretion in infection by sever fever with thrombocytopenia syndrome virus. Sci Rep. 2022;2022(12):2573. https:\/\/doi.org\/10.1038\/s41598-022-06229-0.","journal-title":"Sci Rep"},{"key":"707_CR40","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/METH.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method. Methods. 2001;25:402\u20138. https:\/\/doi.org\/10.1006\/METH.2001.1262.","journal-title":"Methods"},{"key":"707_CR41","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/J.BIOMATERIALS.2016.03.003","volume":"90","author":"Y Lu","year":"2016","unstructured":"Lu Y, Xu S, Chen H, He M, Deng Y, Cao Z, et al. CdSe\/ZnS quantum dots induce hepatocyte pyroptosis and liver inflammation via NLRP3 inflammasome activation. Biomaterials. 2016;90:27\u201339. https:\/\/doi.org\/10.1016\/J.BIOMATERIALS.2016.03.003.","journal-title":"Biomaterials"},{"key":"707_CR42","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/J.CIS.2012.08.002","volume":"183\u2013184","author":"NB Mahale","year":"2012","unstructured":"Mahale NB, Thakkar PD, Mali RG, Walunj DR, Chaudhari SR. Niosomes: novel sustained release nonionic stable vesicular systems \u2014 an overview. Adv Colloid Interface Sci. 2012;183\u2013184:46\u201354. https:\/\/doi.org\/10.1016\/J.CIS.2012.08.002.","journal-title":"Adv Colloid Interface Sci"},{"key":"707_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/J.REPROTOX.2024.108653","volume":"128","author":"A Makipour","year":"2024","unstructured":"Makipour A, Hosseinifar S, Khazaeel K, Tabandeh MR, Jamshidian J. Protective effect of Chlorella vulgaris on testicular damage, sperm parameters, androgen production, apoptosis and oxidative stress index in male rats following doxorubicin administration. Reprod Toxicol. 2024;128:108653. https:\/\/doi.org\/10.1016\/J.REPROTOX.2024.108653.","journal-title":"Reprod Toxicol"},{"key":"707_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/J.TAAP.2025.117337","volume":"499","author":"MF Mansour","year":"2025","unstructured":"Mansour MF, Behairy A, Mostafa M, Khamis T, Alsemeh AE, Ahmed NMQ, et al. Quercetin-loaded PEGylated liposomes alleviate testicular dysfunction in alloxan-induced diabetic rats: the role of Kisspeptin\/Neurokinin B\/Dynorphin pathway. Toxicol Appl Pharmacol. 2025;499:117337. https:\/\/doi.org\/10.1016\/J.TAAP.2025.117337.","journal-title":"Toxicol Appl Pharmacol"},{"key":"707_CR45","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12539","author":"A Meredith","year":"2016","unstructured":"Meredith A. Increasing role of the cancer chemotherapeutic doxorubicin in cellular metabolism. J Pharm Pharmacol. 2016. https:\/\/doi.org\/10.1111\/jphp.12539.","journal-title":"J Pharm Pharmacol"},{"key":"707_CR46","doi-asserted-by":"publisher","unstructured":"Hales, D.B., Allen, J.A., Shankara, T., Janus, P., Buck, S., Diemer, T., Hales, K.H., 2005. Mitochondrial function in Leydig cell steroidogenesis. Wiley Online LibraryDB Hales, JA Allen, T Shankara, P Janus, S Buck, T Diemer, KH HalesAnnals of the New York Academy of Sciences, 2005\u2022Wiley Online Library 1061, 120\u2013134. https:\/\/doi.org\/10.1196\/annals.1336.014","DOI":"10.1196\/annals.1336.014"},{"key":"707_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/J.MTBIO.2023.100837","volume":"23","author":"A Moammeri","year":"2023","unstructured":"Moammeri A, Chegeni MM, Sahrayi H, Ghafelehbashi R, Memarzadeh F, Mansouri A, et al. Current advances in niosomes applications for drug delivery and cancer treatment. Materials Today Bio. 2023;23:100837. https:\/\/doi.org\/10.1016\/J.MTBIO.2023.100837.","journal-title":"Materials Today Bio"},{"issue":"22","key":"707_CR48","doi-asserted-by":"publisher","first-page":"12735","DOI":"10.3390\/IJMS222312735","volume":"2021","author":"OO Oduwole","year":"2021","unstructured":"Oduwole OO, Huhtaniemi IT, Misrahi M. The roles of luteinizing hormone, follicle-stimulating hormone and testosterone in spermatogenesis and folliculogenesis revisited. Int J Mol Sci. 2021;2021(22):12735. https:\/\/doi.org\/10.3390\/IJMS222312735.","journal-title":"Int J Mol Sci"},{"key":"707_CR49","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","volume":"95","author":"H Ohkawa","year":"1979","unstructured":"Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351\u20138. https:\/\/doi.org\/10.1016\/0003-2697(79)90738-3.","journal-title":"Anal Biochem"},{"key":"707_CR50","doi-asserted-by":"publisher","unstructured":"Oyovwi, M.O., Ben-Azu, B., Tesi, E.P., Ojetola, A.A., Olowe, T.G., Joseph, U.G., Emojevwe, V., Oghenetega, O.B., Rotu Rume A, Rotu Rotu A, Falajiki, F.Y., 2024. Diosmin protects the testicles from doxorubicin-induced damage by increasing steroidogenesis and suppressing oxido-inflammation and apoptotic mediators. Int J Biochem Mol Biol 15: 34. https:\/\/doi.org\/10.62347\/ORPK5021","DOI":"10.62347\/ORPK5021"},{"key":"707_CR51","doi-asserted-by":"publisher","first-page":"153","DOI":"10.4062\/BIOMOLTHER.2012.093","volume":"21","author":"JS Park","year":"2013","unstructured":"Park JS, Han K. The Spermatogenic Effect of Yacon Extract and Its Constituents and Their Inhibition Effect of Testosterone Metabolism. Biomol Ther (Seoul). 2013;21:153. https:\/\/doi.org\/10.4062\/BIOMOLTHER.2012.093.","journal-title":"Biomol Ther (Seoul)"},{"key":"707_CR52","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1049\/iet-nbt.2018.5114","volume":"12","author":"S Pattnaik","year":"2018","unstructured":"Pattnaik S, Barik S, Muralitharan G, Busi S. Ferulic acid encapsulated chitosantripolyphosphate nanoparticles attenuate quorum sensing regulated virulence and biofilm formation in Pseudomonas aeruginosaPAO1. IET Nanobiotechnol. 2018;12:1056\u201361. . https:\/\/doi.org\/10.1049\/iet-nbt.2018.5114","journal-title":"IET Nanobiotechnol"},{"key":"707_CR53","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/J.IJPHARM.2007.01.031","volume":"337","author":"E Pereverzeva","year":"2007","unstructured":"Pereverzeva E, Treschalin I, Bodyagin D, Maksimenko O, Langer K, Dreis S, et al. Influence of the formulation on the tolerance profile of nanoparticle-bound doxorubicin in healthy rats: Focus on cardio- and testicular toxicity. Int J Pharm. 2007;337:346\u201356. https:\/\/doi.org\/10.1016\/J.IJPHARM.2007.01.031.","journal-title":"Int J Pharm"},{"key":"707_CR54","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/J.CTRV.2008.05.004","volume":"34","author":"R Petrioli","year":"2008","unstructured":"Petrioli R, Fiaschi AI, Francini E, Pascucci A, Francini G. The role of doxorubicin and epirubicin in the treatment of patients with metastatic hormone-refractory prostate cancer. Cancer Treat Rev. 2008;34:710\u20138. https:\/\/doi.org\/10.1016\/J.CTRV.2008.05.004.","journal-title":"Cancer Treat Rev"},{"key":"707_CR55","doi-asserted-by":"publisher","first-page":"339","DOI":"10.14740\/CR1416","volume":"13","author":"E Podyacheva","year":"2022","unstructured":"Podyacheva E, Shmakova T, Kushnareva E, Onopchenko A, Martynov M, Andreeva D, et al. Modeling doxorubicin-induced cardiomyopathy with fibrotic myocardial damage in Wistar rats. Cardiol Res. 2022;13:339. https:\/\/doi.org\/10.14740\/CR1416.","journal-title":"Cardiol Res"},{"key":"707_CR56","doi-asserted-by":"publisher","DOI":"10.15252\/EMBJ.2018100376","author":"G Ren","year":"2019","unstructured":"Ren G, Zhang X, Xiao Y, Zhang W, Wang Y, Ma W, et al. ABRO1 promotes NLRP3 inflammasome activation through regulation of NLRP3 deubiquitination. EMBO J. 2019. https:\/\/doi.org\/10.15252\/EMBJ.2018100376.","journal-title":"EMBO J"},{"key":"707_CR57","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/CBF.2983","volume":"32","author":"S Roy","year":"2014","unstructured":"Roy S, Metya SK, Rahaman N, Sannigrahi S, Ahmed F. Ferulic acid in the treatment of post-diabetes testicular damage: relevance to the down regulation of apoptosis correlates with antioxidant status via modulation of TGF-\u03b21, IL-1\u03b2 and Akt signalling. Cell Biochem Funct. 2014;32:115\u201324. https:\/\/doi.org\/10.1002\/CBF.2983.","journal-title":"Cell Biochem Funct"},{"key":"707_CR58","doi-asserted-by":"publisher","first-page":"7659765","DOI":"10.1155\/2022\/7659765","volume":"2022","author":"A Salimi","year":"2022","unstructured":"Salimi A, Kheiripour N, Fathi Jouzdani A, Ghasemi H, Soleimani Asl S, Ghafouri-Khosrowshahi A, et al. Nanocurcumin improves lipid status, oxidative stress, and function of the liver in aluminium phosphide-induced toxicity: cellular and molecular mechanisms. Biomed Res Int. 2022;2022:7659765. https:\/\/doi.org\/10.1155\/2022\/7659765.","journal-title":"Biomed Res Int"},{"issue":"1479","key":"707_CR59","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1039\/d3na01016c","volume":"6","author":"S Sangkana","year":"2024","unstructured":"Sangkana S, Eawsakul K, Ongtanasup T, Boonhok R, Mitsuwan W, Chimplee S, Paul AK, Saravanabhavan SS, Mahboob T, Nawaz M, Pereira ML, Wilairatana P, Wiart C, Nissapatorn V. Preparation and evaluation of a niosomal delivery system containing G. mangostana extract and study of its anti-Acanthamoeba activity. Nanoscale Adv. 2024;6(1479):1467. https:\/\/doi.org\/10.1039\/d3na01016c","journal-title":"Nanoscale Adv"},{"issue":"9","key":"707_CR60","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"2012","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;2012(9):671\u20135. https:\/\/doi.org\/10.1038\/nmeth.2089.","journal-title":"Nat Methods"},{"key":"707_CR61","doi-asserted-by":"publisher","DOI":"10.1016\/J.JDDST.2025.107111","volume":"111","author":"SRO Shajan","year":"2025","unstructured":"Shajan SRO, Walikar SK, Sadashivappa NM, Hanumanthappa D, Dinesh BGH, Kumar BS, et al. Folic acid-conjugated Ferulic acid-entangled Single-Walled Carbon Nanotubes: A targeted therapeutic approach for effective breast cancer treatment. J Drug Deliv Sci Technol. 2025;111:107111. https:\/\/doi.org\/10.1016\/J.JDDST.2025.107111.","journal-title":"J Drug Deliv Sci Technol"},{"key":"707_CR62","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/J.MOLLIQ.2017.01.077","volume":"230","author":"F Shakeel","year":"2017","unstructured":"Shakeel F, Imran M, Abida H, N., Alanazi, F.K., Alsarra, I.A.,. J Mol Liq. 2017;230:511\u20137. https:\/\/doi.org\/10.1016\/J.MOLLIQ.2017.01.077.","journal-title":"J Mol Liq"},{"issue":"3","key":"707_CR63","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.eururo.2012.06.022","volume":"62","author":"MG Showell","year":"2012","unstructured":"Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Re: Antioxidants for male subfertility. Eur Urol. 2012;62(3):566\u20137.","journal-title":"Eur Urol"},{"key":"707_CR64","doi-asserted-by":"publisher","first-page":"4855","DOI":"10.1021\/jf0735073","volume":"56","author":"M Singh","year":"2008","unstructured":"Singh M, Arseneault M, Sanderson T, Murthy V, Ramassamy C. Challenges for research on polyphenols from foods in Alzheimer\u2019s disease: Bioavailability, metabolism, and cellular and molecular mechanisms. J Agric Food Chem. 2008;56:4855\u201373. https:\/\/doi.org\/10.1021\/jf0735073.","journal-title":"J Agric Food Chem"},{"key":"707_CR65","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/0006-2952(95)02093-4","volume":"51","author":"DM Stocco","year":"1996","unstructured":"Stocco DM, Clark BJ. Role of the steroidogenic acute regulatory protein (StAR) in steroidogenesis. Biochem Pharmacol. 1996;51:197\u2013205. https:\/\/doi.org\/10.1016\/0006-2952(95)02093-4.","journal-title":"Biochem Pharmacol"},{"issue":"6","key":"707_CR66","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1080\/15376520500194783","volume":"15","author":"AR Sudheer","year":"2005","unstructured":"Sudheer AR, Chandran K, Marimuthu S, Menon VP. Ferulic acid modulates altered lipid profiles and prooxidant\/antioxidant status in circulation during nicotine-induced toxicity: a dose-dependent study. Toxicol Mech Methods. 2005;15(6):375\u201381.","journal-title":"Toxicol Mech Methods"},{"key":"707_CR67","unstructured":"Sudha M 2011. Protective effect of spirulina on doxorubicin induced testicular toxicity. Research Journal of Pharmaceutical Science and Biotechnology, 1(1)."},{"key":"707_CR68","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1093\/HUMUPD\/DMN004","volume":"14","author":"K Tremellen","year":"2008","unstructured":"Tremellen K. Oxidative stress and male infertility\u2013a clinical perspective. Hum Reprod Update. 2008;14:243\u201358. https:\/\/doi.org\/10.1093\/HUMUPD\/DMN004.","journal-title":"Hum Reprod Update"},{"issue":"11","key":"707_CR69","doi-asserted-by":"publisher","first-page":"5522","DOI":"10.1038\/s41598-021-85026-7","volume":"2021","author":"GA Ujah","year":"2021","unstructured":"Ujah GA, Nna VU, Suleiman JB, Eleazu C, Nwokocha C, Rebene JA, et al. Tert-butylhydroquinone attenuates doxorubicin-induced dysregulation of testicular cytoprotective and steroidogenic genes, and improves spermatogenesis in rats. Sci Rep. 2021;2021(11):5522. https:\/\/doi.org\/10.1038\/s41598-021-85026-7.","journal-title":"Sci Rep"},{"key":"707_CR70","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/J.CLINBIOCHEM.2018.03.012","volume":"62","author":"M Vander Borght","year":"2018","unstructured":"Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem. 2018;62:2\u201310. https:\/\/doi.org\/10.1016\/J.CLINBIOCHEM.2018.03.012.","journal-title":"Clin Biochem"},{"key":"707_CR71","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/J.TRSL.2022.05.001","volume":"248","author":"B Ye","year":"2022","unstructured":"Ye B, Shi X, Xu J, Dai S, Xu J, Fan X, et al. Gasdermin D mediates doxorubicin-induced cardiomyocyte pyroptosis and cardiotoxicity via directly binding to doxorubicin and changes in mitochondrial damage. Transl Res. 2022;248:36\u201350. https:\/\/doi.org\/10.1016\/J.TRSL.2022.05.001.","journal-title":"Transl Res"},{"key":"707_CR72","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1159\/000491755","volume":"31","author":"K Zdu\u0144ska","year":"2018","unstructured":"Zdu\u0144ska K, Dana A, Kolodziejczak A, Rotsztejn H. Antioxidant properties of Ferulic acid and its possible application. Skin Pharmacol Physiol. 2018;31:332\u20136. https:\/\/doi.org\/10.1159\/000491755.","journal-title":"Skin Pharmacol Physiol"},{"key":"707_CR73","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/J.FERTNSTERT.2017.06.005","volume":"108","author":"F Zegers-Hochschild","year":"2017","unstructured":"Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The International glossary on infertility and fertility care, 2017. Fertil Steril. 2017;108:393\u2013406. https:\/\/doi.org\/10.1016\/J.FERTNSTERT.2017.06.005.","journal-title":"Fertil Steril"},{"key":"707_CR74","doi-asserted-by":"publisher","first-page":"119823","DOI":"10.1016\/J.BBAMCR.2024.119823","volume":"1871","author":"BK Ziehr","year":"2024","unstructured":"Ziehr BK, MacDonald JA. Regulation of NLRPs by reactive oxygen species: a story of crosstalk Biochimica et Biophysica Acta (BBA). Mol Cell Res. 2024;1871:119823. https:\/\/doi.org\/10.1016\/J.BBAMCR.2024.119823.","journal-title":"Mol Cell Res"},{"issue":"15","key":"707_CR75","doi-asserted-by":"publisher","first-page":"10979","DOI":"10.1038\/s41598-024-81175-7","volume":"2025","author":"MH Zohny","year":"2025","unstructured":"Zohny MH, El-Far YM, Kabil MF, El-Swefy SE, El-Sherbiny IM, El-Shishtawy MM. Ferulic acid lipid nano capsules versus its native form in alleviating diabetic nephropathy induced in rats through TGF-\u03b21\/Hippo pathway crosstalk modulation. Sci Rep. 2025;2025(15):10979. https:\/\/doi.org\/10.1038\/s41598-024-81175-7.","journal-title":"Sci Rep"}],"container-title":["Biological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40659-026-00707-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40659-026-00707-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40659-026-00707-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:04:42Z","timestamp":1785449082000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40659-026-00707-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["707"],"URL":"https:\/\/doi.org\/10.1186\/s40659-026-00707-9","relation":{},"ISSN":["0717-6287"],"issn-type":[{"value":"0717-6287","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"assertion":[{"value":"7 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal experiments were performed in compliance with the ARRIVE guidelines and in accordance with the U.K. Animals (Scientific Procedures) Act, 1986, EU Directive 2010\/63\/EU, and the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978). The ethics committee of the Faculty of Veterinary Medicine at Zagazig University, Egypt, examined and approved the research protocol (approval number: ZUIACUC\/2\/F\/191\/2025). All procedures were carried out in compliance with the relevant laws and regulations. The authors declare, under their legal and civil personal responsibility, that these regulations and guidelines were strictly followed.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors have agreed to publish this manuscript.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest.","order":3,"name":"Ethics","label":"Competing interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"43"}}