{"doi":"10.3892/etm.2020.9573","title":"4-Octyl itaconate (4-OI) attenuates lipopolysaccharide-induced acute lung injury by suppressing PI3K/Akt/NF-κB signaling pathways in mice","abstract":null,"journal":"Experimental and Therapeutic Medicine","year":2020,"id":609167,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1565589,"name":"Lili Zou","orcid":null,"position":1,"is_corresponding":false},{"id":1565590,"name":"Shuhui Lang","orcid":null,"position":2,"is_corresponding":false},{"id":476576,"name":"Yan Xin","orcid":"0000-0001-9291-5061","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"4-Octyl itaconate (4-OI) attenuates lipopolysaccharide-induced acute lung injury by suppressing PI3K/Akt/NF-κB signaling pathways in mice","abstract":"The progression of acute lung injury (ALI) is attributable to inflammation and oxidative stress. The cell-permeable itaconate analog 4-octyl itaconate (4-OI) provides protection against inflammatory responses and oxidative stress. However, whether 4-OI can protect against ALI remains poorly understood. The aim of this study was to explore the protective effects of 4-OI against LPS-induced ALI and the underlying mechanisms using hematoxylin and eosin (H&amp;E) to observe lung morphology, ELISA and reverse transcription-quantitative PCR to measure the levels of IL-1β, TNF-α and IL-6 and western blotting to examine the levels of PI3K, Akt and NF-κB. The present study demonstrates that intraperitoneal administration of 4-OI (25 mg/kg) 2 h before lipopolysaccharide (LPS; 5 mg/kg) intratracheal injection significantly alleviated the lung tissue injury induced by LPS, reducing the production of proinflammatory cytokines and reactive oxygen species (ROS) <em>in vivo</em>. Furthermore, 4-OI and the antioxidant N-acetyl-L-cysteine markedly suppressed PI3K and Akt phosphorylation in LPS-treated RAW264.7 macrophage cells <em>in vitro</em>. Further study demonstrated that a pharmacological inhibitor of the phosphoinositide 3-kinase (PI3K)-Akt pathway, LY294002, inhibited the expression of NF-κB p65 in the nuclear fraction and decreased the production of inflammatory cytokines. Collectively, the experimental results of the present study provide evidence that 4-OI significantly decreased LPS-induced lung inflammation by suppressing ROS-mediated PI3K/Akt/NF-κB signaling pathways. These results suggest that 4-OI could be a valuable therapeutic drug in the treatment of ALI.","is_dataset_classified":null,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33456508","pmcid":"PMC7791918","openalex_id":"https://openalex.org/W3111448160","authors":[],"funders":[],"total_grants":0,"fwci":1.3639,"citation_percentile":0.81664759,"influential_citations":0,"citation_trend":[{"year":2021,"count":2},{"year":2022,"count":9},{"year":2023,"count":6},{"year":2024,"count":9},{"year":2025,"count":6},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.spandidos-publications.com/10.3892/etm.2020.9573/download","host_type":"journal"},{"url":"https://www.spandidos-publications.com/10.3892/etm.2020.9573/download","host_type":"publisher"},{"url":"https://doi.org/10.3892/etm.2020.9573","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33456508","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7791918","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7791918","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7791918?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Immune Response and Inflammation","NF-κB Signaling Pathways","Genomics, phytochemicals, and oxidative stress"],"mesh_terms":[],"keywords":["Protein kinase B","PI3K/AKT/mTOR pathway","Proinflammatory cytokine","Oxidative stress","Pharmacology","Lipopolysaccharide","LY294002","Inflammation","Reactive oxygen species","Chemistry","NF-κB","Signal transduction","Medicine","Immunology","Biochemistry","Acute Lung Injury","4-Octyl Itaconate"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T04:03:35.000521Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}