Nobiletin reduces 5-FU-induced lung injury with antioxidative, anti-inflammatory and anti-apoptotic activities

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dc.authoridAYGORMEZ, Serpil/0000-0002-5675-5096
dc.contributor.authorUslu, Gozde Atila
dc.contributor.authorUslu, Hamit
dc.contributor.authorCoban, Taha Abdulkadir
dc.contributor.authorOzkaraca, Mustafa
dc.contributor.authorMendil, Ali Sefa
dc.contributor.authorAygormez, Serpil
dc.date.accessioned2025-05-04T16:47:28Z
dc.date.available2025-05-04T16:47:28Z
dc.date.issued2025
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractLike 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 + 5-FU groups. Nobiletin and Nobiletin + 5-FU groups received 10 mg/kg Nobiletin i.g. for 7 days. On day 8, 100 mg/kg 5-FU was administered i.p. to 5-FU and Nobiletin + 5-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 kappa B and IL-1 beta 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 kappa B and IL-1 beta levels and supported the normal development of animals. Our results showed that nobiletin pretreatment showed anti-inflammatory activity by inhibiting the NF kappa B 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.
dc.description.sponsorshipScientific and Technological Research Council of Turkiye (TUBITAK)
dc.description.sponsorshipOpen access funding provided by the Scientific and Technological Research Council of Turkiye (TUBITAK).
dc.identifier.doi10.1007/s00210-024-03773-6
dc.identifier.issn0028-1298
dc.identifier.issn1432-1912
dc.identifier.pmid39820543
dc.identifier.scopus2-s2.0-85217230354
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1007/s00210-024-03773-6
dc.identifier.urihttps://hdl.handle.net/20.500.12418/35638
dc.identifier.wosWOS:001399457900001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofNaunyn-Schmiedebergs Archives of Pharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250504
dc.subject5-Fluorouracil
dc.subjectNobiletin
dc.subjectInflammation
dc.subjectApoptosis
dc.subjectOxidative stress
dc.subjectLung damage
dc.titleNobiletin reduces 5-FU-induced lung injury with antioxidative, anti-inflammatory and anti-apoptotic activities
dc.typeArticle

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