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D-carvone attenuates LPS-induced acute lung injury via TLR4/NF-κB and Nrf2/HO-1 signaling pathways in ratsUlaş, NergisÜstündağ, HilalÖzkanlar, SeçkinErbaş, ElifKara, AdemÖzkanlar, YunusemreApoptosisCytokinesD-carvoneInflammationLung injuryOxidative stressSepsisAcute Lung InjuryAnimalsAnti-Inflammatory AgentsAntioxidantsCyclohexane MonoterpenesHeme Oxygenase (Decyclizing)LipopolysaccharidesLungMaleNF-E2-Related Factor 2NF-kappa BRatsRats, Sprague-DawleyRats, WistarSignal TransductionToll-Like Receptor 4beta actincarvonecaspase 3glutathioneheme oxygenase 1immunoglobulin enhancer binding proteininterleukin 1betaAcute lung injury (ALI) is a severe respiratory disorder associated with high morbidity and mortality. Lipopolysaccharide (LPS) is widely used to induce ALI in animal models. D-carvone, a natural monoterpene, has been reported to possess anti-inflammatory and antioxidant properties. This study aimed to investigate the protective effects of D-carvone on LPS-induced ALI in rats. Thirty-six male rats were randomly divided into six groups (n = 6): control, D-carvone (10 mg/kg and 20 mg/kg p.o.), LPS (10 mg/kg E. coli lipopolysaccharide i.p.), and LPS + D-carvone (LPS with either 10 or 20 mg/kg D-carvone). D-carvone was administered orally once daily for 10 days. On day 10, sepsis was induced with LPS administration, and samples were collected after 6 h under deep anesthesia. LPS administration caused significant lung injury, as evidenced by increased histopathological scores, upregulation of pro-inflammatory markers (TLR4, IL-1β, TNF-α), and oxidative stress (increased MDA, decreased GSH and SOD). Treatment with D-carvone at both doses significantly attenuated these changes. D-carvone downregulated pro-inflammatory markers, upregulated anti-inflammatory (NRF2) and anti-apoptotic (Bcl-2) proteins, and reduced the levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-8) in lung tissues. In conclusion, D-carvone protects against LPS-induced ALI in rats, possibly through its anti-inflammatory and antioxidant properties. These findings suggest that D-carvone could be a potential therapeutic candidate for preventing and treating ALI. © The Author(s) 2025.Springer Science and Business Media Deutschland GmbH2025Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/10777https://doi.org/10.1007/s00210-025-04024-y0028-1298enNaunyn-Schmiedeberg's Archives of Pharmacologyinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/10777