2026-10-19T04:52:58Zhttps://ebyu-rdlopen.rawdatalibrary.net/oai/request

oai:ebyu-rdlopen.rawdatalibrary.net:ebyu/106922026-10-18T21:13:13Zopenairedrivercom_ebyu_10000col_ebyu_10001

Nobiletin reduces 5-FU-induced lung injury with antioxidative, anti-inflammatory and anti-apoptotic activitiesAtila Uslu, GözdeUslu, HamitÇoban, Taha AbdulkadirÖzkaraca, MustafaMendil, Ali SefaAygörmez, Serpil5-FluorouracilApoptosisInflammationLung damageNobiletinOxidative stressAnimalsAnti-Inflammatory AgentsAntimetabolites, AntineoplasticAntioxidantsFlavonesFluorouracilInterleukin-1betaLungLung InjuryMaleNF-kappa BRats, Wistarcaspase 3glutathioneinterleukin 1betamalonaldehydeprotein Baxprotein bcl 2sodium chlorideantiinflammatory agentantineoplastic antimetaboliteantioxidantflavone derivativeimmunoglobulin enhancer binding proteinLike 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 NFκB and IL-1β 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 NFκB and IL-1β levels and supported the normal development of animals. Our results showed that nobiletin pretreatment showed anti-inflammatory activity by inhibiting the NFκB 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. © The Author(s) 2025.Springer Science and Business Media Deutschland GmbH2025Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/10692https://doi.org/10.1007/s00210-024-03773-60028-1298enNaunyn-Schmiedeberg's Archives of Pharmacologyinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/10692