{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:00:07Z","timestamp":1788969607227,"version":"build-2803163510"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Erzincan Binali Yildirim University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Like other chemotherapeutic agents, 5-fluorouracil (5-FU) targets cancerous cells, but it also causes many unwanted side effects on healthy tissues and cells. Based on the undesirable effects of 5-FU, the aim of this study was to determine how 5-FU affects lung tissue and whether nobiletin has any protective effect. The study consisted of negative control, Nobiletin, 5-FU and Nobiletin\u2009+\u20095-FU groups. Nobiletin and Nobiletin\u2009+\u20095-FU groups received 10\u00a0mg\/kg Nobiletin i.g. for 7\u00a0days. On day 8, 100\u00a0mg\/kg 5-FU was administered i.p. to 5-FU and Nobiletin\u2009+\u20095-FU groups. Biochemical and immunohistochemical analyses were performed on the lung tissues dissected at the end of the study. 5-FU caused growth retardation, disturbed the oxidant-antioxidant balance by increasing MDA levels and decreasing GSH levels, triggered cellular apoptosis by increasing Bax and caspase-3 levels and decreasing Bcl-2, also increased lung tissue inflammation and damage by increasing NF\u03baB and IL-1\u03b2 levels. However, it was determined that Nobiletin prevented the disruption of the oxidant-antioxidant balance, showed significant anti-apoptotic effects, especially by reducing Bax levels and partially modulating caspase-3 and Bcl-2 levels, and also exhibited anti-inflammatory effects by reducing NF\u03baB and IL-1\u03b2 levels and supported the normal development of animals. Our results showed that nobiletin pretreatment showed anti-inflammatory activity by inhibiting the NF\u03baB pathway in 5-FU-induced lung injury, suppressed oxidative stress with its antioxidant activity and was effective in modulating cellular apoptosis with its anti-apoptotic activity. In conclusion, Nobiletin has been shown to have an important potential in reducing fluorouracil-induced tissue damage by acting through multiple pathways.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s00210-024-03773-6","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T05:24:51Z","timestamp":1737091491000},"page":"8543-8554","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Nobiletin reduces 5-FU-induced lung injury with antioxidative, anti-inflammatory and anti-apoptotic activities"],"prefix":"10.1007","volume":"398","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2328-9164","authenticated-orcid":false,"given":"G\u00f6zde","family":"Atila Uslu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3974-5814","authenticated-orcid":false,"given":"Hamit","family":"Uslu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1711-5499","authenticated-orcid":false,"given":"Taha Abdulkadir","family":"\u00c7oban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-4569","authenticated-orcid":false,"given":"Mustafa","family":"\u00d6zkaraca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2722-3290","authenticated-orcid":false,"given":"Ali Sefa","family":"Mendil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5675-5096","authenticated-orcid":false,"given":"Serpil","family":"Ayg\u00f6rmez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"issue":"4","key":"3773_CR1","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1515\/jcim-2016-0043","volume":"13","author":"AK Al-Asmari","year":"2016","unstructured":"Al-Asmari AK, Khan AQ, Al-Asmari SA, Al-Rawi A, Al-Omani S (2016) Alleviation of 5-fluorouracil-induced intestinal mucositis in rats by vitamin E via targeting oxidative stress and inflammatory markers. J Complement Integr Med 13(4):377\u2013385. https:\/\/doi.org\/10.1515\/jcim-2016-0043","journal-title":"J Complement Integr Med"},{"issue":"2","key":"3773_CR2","first-page":"139","volume":"12","author":"MZ Al-Hamdany","year":"2014","unstructured":"Al-Hamdany MZ, Al-Hubaity AY (2014a) Protective effects of N-acetylcysteine against 5-fluorouracil-induced pulmonary toxicity in albino rats. Iraqi J Med Sci 12(2):139\u2013149","journal-title":"Iraqi J Med Sci"},{"issue":"7","key":"3773_CR3","first-page":"734","volume":"64","author":"MZ Al-Hamdany","year":"2014","unstructured":"Al-Hamdany MZ, Al-Hubaity AY (2014b) The structural changes of the rat\u2019s lung induced by intraperitoneal injection of 5-fluorouracil. J Pak Med Assoc 64(7):734\u2013738","journal-title":"J Pak Med Assoc"},{"issue":"6","key":"3773_CR4","doi-asserted-by":"publisher","first-page":"5408","DOI":"10.3892\/mmr.2016.5919","volume":"14","author":"J Bi","year":"2016","unstructured":"Bi J, Zhang H, Lu J, Lei W (2016) Nobiletin ameliorates isoflurane-induced cognitive impairment via antioxidant, anti-inflammatory and anti-apoptotic effects in aging rats. Mol Med Rep 14(6):5408\u20135414. https:\/\/doi.org\/10.3892\/mmr.2016.5919","journal-title":"Mol Med Rep"},{"issue":"5","key":"3773_CR5","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.3390\/antiox12051005","volume":"12","author":"MC Da Silva","year":"2023","unstructured":"Da Silva MC, Fabiano LC, Da Costa Salom\u00e3o KC, De Freitas PLZ, Neves CQ, Borges SC, De Souza Carvalho MDG, Breithaupt-Faloppa AC, De Thomaz AA, Dos Santos AM, Buttow NC (2023) A rodent model of human-dose-equivalent 5-fluorouracil: toxicity in the liver, kidneys, and lungs. Antioxidants 12(5):1005. https:\/\/doi.org\/10.3390\/antiox12051005","journal-title":"Antioxidants"},{"issue":"11","key":"3773_CR6","doi-asserted-by":"publisher","first-page":"6789","DOI":"10.1002\/fsn3.3645","volume":"11","author":"S Daneshvar","year":"2023","unstructured":"Daneshvar S, Zamanian MY, Ivraghi MS, Golmohammadi M, Modanloo M, Kamiab Z, Pourhosseini SME, Heidari M, Bazmandegan G (2023) A comprehensive view on the apigenin impact on colorectal cancer: focusing on cellular and molecular mechanisms. Food Sci Nutr 11(11):6789\u20136801. https:\/\/doi.org\/10.1002\/fsn3.3645","journal-title":"Food Sci Nutr"},{"issue":"5","key":"3773_CR7","doi-asserted-by":"publisher","first-page":"466","DOI":"10.7150\/ijbs.5.466","volume":"5","author":"HI El-Sayyad","year":"2009","unstructured":"El-Sayyad HI, Ismail MF, Shalaby FM, Abou-El-Magd RF, Gaur RL, Fernando A, Raj MHG, Ouhtit A (2009) Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. Int J Biol Sci 5(5):466. https:\/\/doi.org\/10.7150\/ijbs.5.466","journal-title":"Int J Biol Sci"},{"key":"3773_CR8","doi-asserted-by":"publisher","unstructured":"Gedikli S, Erbas E (2021) Protective effects of naringin on lung toxicity induced by 5-fluorouracil in rats. Kocatepe Vet J 14(1):16\u201325. https:\/\/doi.org\/10.30607\/kvj.782356","DOI":"10.30607\/kvj.782356"},{"issue":"7","key":"3773_CR9","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.apjtb.2017.06.013","volume":"7","author":"V Gelen","year":"2017","unstructured":"Gelen V, \u015eeng\u00fcl E, Gedikli S, Atila G, Uslu H, Makav M (2017) The protective effect of rutin and quercetin on 5-FU-induced hepatotoxicity in rats. Asian Pac J Trop Biomed 7(7):647\u2013653. https:\/\/doi.org\/10.1016\/j.apjtb.2017.06.013","journal-title":"Asian Pac J Trop Biomed"},{"key":"3773_CR10","doi-asserted-by":"publisher","first-page":"47046","DOI":"10.1007\/s11356-021-13969-5","volume":"28","author":"V Gelen","year":"2021","unstructured":"Gelen V, Sengul E, Yildirim SE, Tekin S, K\u00fck\u00fcrt A (2021) The protective effects of hesperidin and curcumin on 5-fluorouracil\u2013induced nephrotoxicity in mice. Environ Sci Pollut Res 28:47046\u201347055. https:\/\/doi.org\/10.1007\/s11356-021-13969-5","journal-title":"Environ Sci Pollut Res"},{"issue":"12","key":"3773_CR11","doi-asserted-by":"publisher","first-page":"7458","DOI":"10.1002\/fsn3.3699","volume":"11","author":"M Golmohammadi","year":"2023","unstructured":"Golmohammadi M, Zamanian MY, Jalal SM, Noraldeen SAM, Ram\u00edrez-Coronel AA, Oudaha KH, Obaid RF, Almulla AF, Bazmandegan G, Kamiab Z (2023) A comprehensive review on Ellagic acid in breast cancer treatment: from cellular effects to molecular mechanisms of action. Food Sci Nutr 11(12):7458\u20137468. https:\/\/doi.org\/10.1002\/fsn3.3699","journal-title":"Food Sci Nutr"},{"issue":"2","key":"3773_CR12","doi-asserted-by":"publisher","first-page":"e22427","DOI":"10.1002\/jbt.22427","volume":"34","author":"M G\u00fcven\u00e7","year":"2020","unstructured":"G\u00fcven\u00e7 M, Cellat M, G\u00f6k\u00e7ek \u0130, \u00d6zkan H, Arkal\u0131 G, Yakan A, \u00d6zsoy \u015eY, Aksakal M (2020) Nobiletin attenuates acetaminophen-induced hepatorenal toxicity in rats. J Biochem Mol Toxicol 34(2):e22427. https:\/\/doi.org\/10.1002\/jbt.22427","journal-title":"J Biochem Mol Toxicol"},{"issue":"2","key":"3773_CR13","first-page":"1070","volume":"25","author":"H Jiang","year":"2020","unstructured":"Jiang H, Chen H, Jin C, Mo J, Wang H (2020) Nobiletin flavone inhibits the growth and metastasis of human pancreatic cancer cells via induction of autophagy, G0\/G1 cell cycle arrest and inhibition of NF-kB signalling pathway. J Buon 25(2):1070\u20131075","journal-title":"J Buon"},{"issue":"2","key":"3773_CR14","first-page":"146","volume":"11","author":"N Kheiripour","year":"2021","unstructured":"Kheiripour N, Khodamoradi Z, Ranjbar A, Borzouei S (2021) The positive effect of short-term nano-curcumin therapy on insulin resistance and serum levels of afamin in patients with metabolic syndrome. Avicenna J Phytomed 11(2):146\u2013153","journal-title":"Avicenna J Phytomed"},{"issue":"4","key":"3773_CR15","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/s41419-022-04826-5","volume":"13","author":"E Kim","year":"2022","unstructured":"Kim E, Kim YJ, Ji Z, Kang JM, Wirianto M, Paudel KR, Smith JA, Ono K, Kim JA, Eckel-Mahan K, Zhou X, Lee HK, Joo YJ, Yoo SH, Chen Z (2022) ROR activation by Nobiletin enhances antitumor efficacy via suppression of I\u03baB\/NF-\u03baB signaling in triple-negative breast cancer. Cell Death Dis 13(4):374. https:\/\/doi.org\/10.1038\/s41419-022-04826-5","journal-title":"Cell Death Dis"},{"issue":"12","key":"3773_CR16","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1248\/bpb.30.2317","volume":"30","author":"N Koga","year":"2007","unstructured":"Koga N, Matsuo M, Ohta C, Haraguchi K, Matsuoka M, Kato Y, Ishii T, Yano M, Ohta H (2007) Comparative study on nobiletin metabolism with liver microsomes from rats, guinea pigs and hamsters and rat cytochrome P450. Biol Pharm Bull 30(12):2317\u20132323. https:\/\/doi.org\/10.1248\/bpb.30.2317","journal-title":"Biol Pharm Bull"},{"issue":"6","key":"3773_CR17","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1093\/jjco\/hye057","volume":"31","author":"E Kurakawa","year":"2001","unstructured":"Kurakawa E, Kasuga I, Ishizuka S, Yoshida T, Kunisawa A, Minemura K, Utsumi K, Ohyashiki K (2001) Interstitial pneumonia possibly due to a novel anticancer drug, TS-1: first case report. Jpn J Clin Oncol 31(6):284\u2013286. https:\/\/doi.org\/10.1093\/jjco\/hye057","journal-title":"Jpn J Clin Oncol"},{"issue":"4","key":"3773_CR18","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1248\/bpb.b18-00707","volume":"42","author":"H Lim","year":"2019","unstructured":"Lim H, Kim SY, Lee E, Lee S, Oh S, Jung J, Kim KS, Moon A (2019) Sex-dependent adverse drug reactions to 5-fluorouracil in colorectal cancer. Biol Pharm Bull 42(4):594\u2013600. https:\/\/doi.org\/10.1248\/bpb.b18-00707","journal-title":"Biol Pharm Bull"},{"key":"3773_CR19","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.ejphar.2019.03.056","volume":"854","author":"F Liu","year":"2019","unstructured":"Liu F, Zhang H, Li Y, Lu X (2019) Nobiletin suppresses oxidative stress and apoptosis in H9c2 cardiomyocytes following hypoxia\/reoxygenation injury. Eur J Pharmacol 854:48\u201353. https:\/\/doi.org\/10.1016\/j.ejphar.2019.03.056","journal-title":"Eur J Pharmacol"},{"issue":"1","key":"3773_CR20","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.neulet.2010.07.078","volume":"484","author":"YH Lu","year":"2010","unstructured":"Lu YH, Su MY, Huang HY, Yuan CG (2010) Protective effects of the citrus flavanones to PC12 cells against cytotoxicity induced by hydrogen peroxide. Neurosci Lett 484(1):6\u201311. https:\/\/doi.org\/10.1016\/j.neulet.2010.07.078","journal-title":"Neurosci Lett"},{"key":"3773_CR21","doi-asserted-by":"publisher","first-page":"970","DOI":"10.4161\/cbt.7.6.5967","volume":"7","author":"G Luo","year":"2008","unstructured":"Luo G, Guan X, Zhou L (2008) Apoptotic effect of citrus fruit extract nobiletin on lung cancer cell line A549 in vitro and in vivo. Cancer Biol Ther 7:970\u2013977. https:\/\/doi.org\/10.4161\/cbt.7.6.5967","journal-title":"Cancer Biol Ther"},{"issue":"7\u20138","key":"3773_CR22","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.etp.2015.04.008","volume":"67","author":"S Malik","year":"2015","unstructured":"Malik S, Bhatia J, Suchal K, Gamad N, Dinda AK, Gupta YK, Arya DS (2015) Nobiletin ameliorates cisplatin-induced acute kidney injury due to its anti-oxidant, anti-inflammatory and anti-apoptotic effects. Exp Toxicol Pathol 67(7\u20138):427\u2013433. https:\/\/doi.org\/10.1016\/j.etp.2015.04.008","journal-title":"Exp Toxicol Pathol"},{"issue":"1","key":"3773_CR23","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1021\/jf1033224","volume":"59","author":"JA Manthey","year":"2011","unstructured":"Manthey JA, Cesar TB, Jackson E, Mertens-Talcott S (2011) Pharmacokinetic study of nobiletin and tangeretin in rat serum by high-performance liquid chromatography\u2212 electrospray ionization\u2212 mass spectrometry. J Agric Food Chem 59(1):145\u2013151. https:\/\/doi.org\/10.1021\/jf1033224","journal-title":"J Agric Food Chem"},{"issue":"7","key":"3773_CR24","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1200\/JCO.1992.10.7.1171","volume":"10","author":"G Milano","year":"1992","unstructured":"Milano G, Etienne MC, Cassuto-Viguier E, Thyss A, Santini J, Frenay M, Renee N, Schneider M, Demard F (1992) Influence of sex and age on fluorouracil clearance. J Clin Oncol 10(7):1171\u20131175. https:\/\/doi.org\/10.1200\/JCO.1992.10.7.1171","journal-title":"J Clin Oncol"},{"issue":"3","key":"3773_CR25","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.3390\/cancers2031717","volume":"2","author":"K Miura","year":"2010","unstructured":"Miura K, Kinouchi M, Ishida K, Fujibuchi W, Naitoh T, Ogawa H, Ando T, Yazaki N, Watanabe K, Heneda S, Shibata C, Sasaki I (2010) 5-fu metabolism in cancer and orally-administrable 5-fu drugs. Cancers 2(3):1717\u20131730. https:\/\/doi.org\/10.3390\/cancers2031717","journal-title":"Cancers"},{"issue":"22","key":"3773_CR26","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.2174\/1381612829666230426115424","volume":"29","author":"R Moazamiyanfar","year":"2023","unstructured":"Moazamiyanfar R, Rezaei S, AliAshrafzadeh H, Rastegar-Pouyani N, Jafarzadeh E, Mouludi KE, Khodamoradi E, Zhaleh M, Taeb S, Najafi M (2023) Nobiletin in cancer therapy; mechanisms and therapy perspectives. Curr Pharm des 29(22):1713\u20131728. https:\/\/doi.org\/10.2174\/1381612829666230426115424","journal-title":"Curr Pharm des"},{"key":"3773_CR27","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.canlet.2006.11.016","volume":"251","author":"KL Morley","year":"2007","unstructured":"Morley KL, Ferguson PJ, Koropatnick J (2007) Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells. Cancer Lett 251:168\u2013178. https:\/\/doi.org\/10.1016\/j.canlet.2006.11.016","journal-title":"Cancer Lett"},{"key":"3773_CR28","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.3892\/ol.2016.4793","volume":"12","author":"A Nagappan","year":"2016","unstructured":"Nagappan A, Lee HJ, Saralamma VVG, Park HS, Hong GE, Yumnam S, Raha S, Charles SN, Shin SC, Kim EH, Lee WS, Kim GS (2016) Flavonoids isolated from Citrus platymamma induced G2\/M cell cycle arrest and apoptosis in A549 human lung cancer cells. Oncol Lett 12:1394\u20131402. https:\/\/doi.org\/10.3892\/ol.2016.4793","journal-title":"Oncol Lett"},{"issue":"2","key":"3773_CR29","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/0003-2697(66)90167-9","volume":"16","author":"ZA Placer","year":"1966","unstructured":"Placer ZA, Cushman LL, Johnson BC (1966) Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem 16(2):359\u2013364. https:\/\/doi.org\/10.1016\/0003-2697(66)90167-9","journal-title":"Anal Biochem"},{"key":"3773_CR30","doi-asserted-by":"publisher","unstructured":"Safarpour S, Pirzadeh M, Ebrahimpour A, Shirafkan F, Madani F, Hosseini M, Moghadamnia AA, Kazemi S (2022a) Protective effect of kaempferol and its nanoparticles on 5-fluorouracil-induced cardiotoxicity in rats. BioMed Res Int 2022(1):2273000.\u00a0https:\/\/doi.org\/10.1155\/2022\/2273000","DOI":"10.1155\/2022\/2273000"},{"key":"3773_CR31","doi-asserted-by":"publisher","unstructured":"Safarpour S, Safarpour S, Pirzadeh M, Moghadamnia AA, Ebrahimpour A, Shirafkan F, Mansoori R, Kazemi S, Hosseini M (2022b) Colchicine ameliorates 5-Fluorouracil-Induced cardiotoxicity in rats. Oxid Med Cell Longev 1:6194532. https:\/\/doi.org\/10.1155\/2022\/6194532","DOI":"10.1155\/2022\/6194532"},{"issue":"8","key":"3773_CR32","doi-asserted-by":"publisher","first-page":"101672","DOI":"10.1016\/j.jsps.2023.06.005","volume":"31","author":"S Safarpour","year":"2023","unstructured":"Safarpour S, Safarpour S, Moghadamnia AA, Kazemi S, Ebrahimpour A, Shirafkan F (2023) The protective effects of silymarin nanoemulsion on 5-fluorouracil-induced gastrointestinal toxicity in rats. Saudi Pharm J 31(8):101672. https:\/\/doi.org\/10.1016\/j.jsps.2023.06.005","journal-title":"Saudi Pharm J"},{"issue":"2","key":"3773_CR33","doi-asserted-by":"publisher","first-page":"407","DOI":"10.3892\/ijo.2018.4661","volume":"54","author":"V Schirrmache","year":"2019","unstructured":"Schirrmache V (2019) From chemotherapy to biological therapy: a review of novel concepts to reduce the side effects of systemic cancer treatment. Int J Oncol 54(2):407\u2013419. https:\/\/doi.org\/10.3892\/ijo.2018.4661","journal-title":"Int J Oncol"},{"key":"3773_CR34","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","volume":"25","author":"J Sedlak","year":"1968","unstructured":"Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman\u2019s reagent. Anal Biochem 25:192\u2013205","journal-title":"Anal Biochem"},{"key":"3773_CR35","doi-asserted-by":"publisher","first-page":"111285","DOI":"10.1016\/j.biopha.2021.111285","volume":"137","author":"C Sethy","year":"2021","unstructured":"Sethy C, Kundu CN (2021) 5-Fluorouracil (5-FU) resistance and the new strategy to enhance the sensitivity against cancer: implication of DNA repair inhibition. Biomed Pharmacother 137:111285. https:\/\/doi.org\/10.1016\/j.biopha.2021.111285","journal-title":"Biomed Pharmacother"},{"issue":"5","key":"3773_CR36","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1007\/s00210-023-02781-2","volume":"397","author":"A Sharma","year":"2024","unstructured":"Sharma A, Jasrotia S, Kumar A (2024) Effects of chemotherapy on the immune system: implications for cancer treatment and patient outcomes. Naunyn-Schmiedeberg\u2019s Arch Pharmacol 397(5):2551\u20132566. https:\/\/doi.org\/10.1007\/s00210-023-02781-2","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol"},{"issue":"1","key":"3773_CR37","doi-asserted-by":"publisher","first-page":"e01179","DOI":"10.1016\/j.heliyon.2019.e01179","volume":"5","author":"CJ Ugwah-Oguejiofor","year":"2019","unstructured":"Ugwah-Oguejiofor CJ, Okoli CO, Ugwah MO, Umaru ML, Ogbulie CS, Mshelia HE, Umar M, Njan AA (2019) Acute and sub-acute toxicity of aqueous extract of aerial parts of Caralluma dalzielii NE Brown in mice and rats. Heliyon 5(1):e01179. https:\/\/doi.org\/10.1016\/j.heliyon.2019.e01179","journal-title":"Heliyon"},{"key":"3773_CR38","first-page":"107","volume-title":"Research & reviews in health sciences-II","author":"GA Uslu","year":"2021","unstructured":"Uslu GA (2021) Protective efficacy of Nobiletin and physiological pathways it uses. In: Evereklip\u011flu C (ed) Research & reviews in health sciences-II. Gece Publishing, Ankara, pp 107\u2013123"},{"issue":"3","key":"3773_CR39","doi-asserted-by":"publisher","first-page":"627","DOI":"10.3390\/cancers14030627","volume":"14","author":"WM Van Den Boogaard","year":"2022","unstructured":"Van Den Boogaard WM, Komninos DS, Vermeij WP (2022) Chemotherapy side-effects: not all DNA damage is equal. Cancers 14(3):627. https:\/\/doi.org\/10.3390\/cancers14030627","journal-title":"Cancers"},{"key":"3773_CR40","doi-asserted-by":"publisher","unstructured":"Vemula S, Mylaram J, Yadala R, Alla G, Banothu A, Veera HDD (2024) Protective effects of naringenin on 5-fluorouracil induced pulmonary toxicity via modulation of NF-KB and Nrf2 pathway. Pak Vet J 44(1):63\u201370. https:\/\/doi.org\/10.29261\/pakvetj\/2024.126","DOI":"10.29261\/pakvetj\/2024.126"},{"key":"3773_CR41","doi-asserted-by":"publisher","unstructured":"Ward RA, Fawell S, Floc\u2019h N, Flemington V, McKerrecher D, Smith PD (2020) Challenges and opportunities in cancer drug resistance. Chem Rev 121(6):3297-3351.\u00a0https:\/\/doi.org\/10.1021\/acs.chemrev.0c00383","DOI":"10.1021\/acs.chemrev.0c00383"},{"issue":"11","key":"3773_CR42","doi-asserted-by":"publisher","first-page":"2935","DOI":"10.1002\/cncr.26595","volume":"118","author":"Y Wettergren","year":"2012","unstructured":"Wettergren Y, Carlsson G, Odin E, Gustavsson B (2012) Pretherapeutic uracil and dihydrouracil levels of colorectal cancer patients are associated with sex and toxic side effects during adjuvant 5-fluorouracil\u2013based chemotherapy. Cancer 118(11):2935\u20132943. https:\/\/doi.org\/10.1002\/cncr.26595","journal-title":"Cancer"},{"key":"3773_CR43","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.jff.2015.09.035","volume":"19","author":"X Wu","year":"2015","unstructured":"Wu X, Song M, Rakariyatham K, Zheng J, Guo S, Tang Z, Zhou S, Xiao H (2015) Anti-inflammatory effects of 4\u2032-demethylnobiletin, a major metabolite of nobiletin. J Funct Foods 19:278\u2013287. https:\/\/doi.org\/10.1016\/j.jff.2015.09.035","journal-title":"J Funct Foods"},{"key":"3773_CR44","doi-asserted-by":"publisher","unstructured":"Xu Z, Wu D, Fu D, Tang C, Ge J, Zhang Z, Zhou W (2020) Nobiletin inhibits viability of human renal carcinoma cells via the JAK2\/STAT3 and PI3K\/Akt pathway. Cell Mol Biol 66(5):199\u2013203. https:\/\/doi.org\/10.14715\/cmb\/2020.66.5.33","DOI":"10.14715\/cmb\/2020.66.5.33"},{"key":"3773_CR45","doi-asserted-by":"publisher","unstructured":"Yamane H, Kamei H, Yamagishi T, Ochi N, Takigawa N (2013) Fatal interstitial pneumonia caused by panitumumab-containing chemotherapy: a case report \u5ddd\u5d0e\u533b\u5b66\u4f1a\u8a8c 39(1):49\u201353. https:\/\/doi.org\/10.11482\/2013\/KMJ31(1)49-53.2013.pdf","DOI":"10.11482\/2013\/KMJ31(1)49-53.2013.pdf"},{"issue":"4","key":"3773_CR46","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.oooo.2020.06.020","volume":"130","author":"J Yang","year":"2020","unstructured":"Yang J, Yang Y, Wang L, Jin Q, Pan M (2020) Nobiletin selectively inhibits oral cancer cell growth by promoting apoptosis and DNA damage in vitro. Oral Surg Oral Med Oral Pathol Oral Radiol 130(4):419\u2013427. https:\/\/doi.org\/10.1016\/j.oooo.2020.06.020","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol"},{"key":"3773_CR47","doi-asserted-by":"publisher","first-page":"7255497","DOI":"10.1155\/2022\/7255497","volume":"2022","author":"QQ Yu","year":"2022","unstructured":"Yu QQ, Zhang H, Guo Y, Han B, Jiang P (2022) The intestinal redox system and its significance in chemotherapy-induced intestinal mucositis. Oxid Med Cell Longev 2022:7255497. https:\/\/doi.org\/10.1155\/2022\/7255497","journal-title":"Oxid Med Cell Longev"},{"issue":"4","key":"3773_CR48","doi-asserted-by":"publisher","first-page":"e4030","DOI":"10.1002\/cbf.4030","volume":"42","author":"MY Zamanian","year":"2024","unstructured":"Zamanian MY, Alsaab HO, Golmohammadi M, Yumashev A, Jabba AM, Abid MK, Joshi A, Alawadi AH, Jafer NS, Kianifar F, Obakiro SB (2024) NF-\u03baB pathway as a molecular target for curcumin in diabetes mellitus treatment: focusing on oxidative stress and inflammation. Cell Biochem Funct 42(4):e4030. https:\/\/doi.org\/10.1002\/cbf.4030","journal-title":"Cell Biochem Funct"},{"issue":"4","key":"3773_CR49","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1002\/mco2.104","volume":"2","author":"T Zhang","year":"2021","unstructured":"Zhang T, Ma C, Zhang Z, Zhang H, Hu H (2021) NF-\u03baB signaling in inflammation and cancer. MedComm 2(4):618\u2013653. https:\/\/doi.org\/10.1002\/mco2.104","journal-title":"MedComm"}],"updated-by":[{"DOI":"10.1007\/s00210-025-04878-2","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000}}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-024-03773-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-024-03773-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-024-03773-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T08:12:40Z","timestamp":1772784760000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-024-03773-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,17]]},"references-count":49,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["3773"],"URL":"https:\/\/doi.org\/10.1007\/s00210-024-03773-6","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,17]]},"assertion":[{"value":"4 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised: Inaccuracies were identified in Figure 9. Specifically, the images in Figures 9C and 9D were incorrectly presented due to the misplacement of the representative image for Figure 9D.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2026","order":8,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":9,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":10,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s00210-025-04878-2","URL":"https:\/\/doi.org\/10.1007\/s00210-025-04878-2","order":11,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Following national and international guidelines, all experimental procedures involving experimental animals were completed. The local ethics committee for animal experiments at Erzincan Binali Y\u0131ld\u0131r\u0131m University granted the necessary permissions for these experimental procedures (protocol number: 2024\/07).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}