{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:23:15Z","timestamp":1787509395991,"version":"build-2736575974"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100009367","name":"Mansoura University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009367","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.ejphar.2025.177873","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T01:54:55Z","timestamp":1750643695000},"page":"177873","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"special_numbering":"C","title":["Rupatadine modulates TLR4\/MYD88\/NF-\u03baB and AKT\/PI3K signaling pathways, attenuating sepsis-induced liver injury in mice"],"prefix":"10.1016","volume":"1002","author":[{"given":"Abeer G.","family":"Sakr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda E.","family":"Kafl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0021-5533","authenticated-orcid":false,"given":"Dalia H.","family":"El-Kashef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2025.177873_bib1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s12011-019-01910-4","article-title":"Curcumin and selenium prevent lipopolysaccharide\/diclofenac-induced liver injury by suppressing inflammation and oxidative stress","volume":"196","author":"Al-Dossari","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"10.1016\/j.ejphar.2025.177873_bib2","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1002\/ijc.24748","article-title":"Akt\u2010mediated regulation of NF\u03baB and the essentialness of NF\u03baB for the oncogenicity of PI3K and akt","volume":"125","author":"Bai","year":"2009","journal-title":"Int. J. Cancer"},{"key":"10.1016\/j.ejphar.2025.177873_bib3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1023\/A:1014489108199","article-title":"Action of E. coli endotoxin, IL-1\u03b2 and TNF-\u03b1 on antioxidant status of cultured hepatocytes","volume":"231","author":"Catal\u00e1","year":"2002","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.ejphar.2025.177873_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2023.121710","article-title":"Modulatory effect of rupatadine on mesenchymal stem cell-derived exosomes in hepatic fibrosis in rats: a potential role for miR-200a","volume":"324","author":"Didamoony","year":"2023","journal-title":"Life Sci."},{"key":"10.1016\/j.ejphar.2025.177873_bib5","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s10787-023-01147-7","article-title":"A novel mechanistic approach for the anti-fibrotic potential of rupatadine in rat liver via amendment of PAF\/NF-\u0138B p65\/TGF-\u03b21 and hedgehog\/HIF-1\u03b1\/VEGF trajectories","volume":"31","author":"Didamoony","year":"2023","journal-title":"Inflammopharmacology."},{"key":"10.1016\/j.ejphar.2025.177873_bib6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.intimp.2018.09.017","article-title":"Nicorandil ameliorates pulmonary inflammation and fibrosis in a rat model of silicosis","volume":"64","author":"El-Kashef","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejphar.2025.177873_bib7","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0003-9861(59)90090-6","article-title":"Tissue sulfhydryl groups","volume":"82","author":"Ellman","year":"1959","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.ejphar.2025.177873_bib8","doi-asserted-by":"crossref","first-page":"837","DOI":"10.3390\/biomedicines9070837","article-title":"Pitavastatin ameliorates lipopolysaccharide-induced blood-brain barrier dysfunction","volume":"9","author":"Fujimoto","year":"2021","journal-title":"Biomedicines."},{"key":"10.1016\/j.ejphar.2025.177873_bib9","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.immuni.2006.08.023","article-title":"The adaptor molecule MyD88 activates PI-3 kinase signaling in CD4+ T cells and enables CpG oligodeoxynucleotide-mediated costimulation","volume":"25","author":"Gelman","year":"2006","journal-title":"Immunity."},{"key":"10.1016\/j.ejphar.2025.177873_bib10","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1042\/CBI20100624","article-title":"Histamine promotes the expression of receptors TLR2 and TLR4 and amplifies sensitivity to lipopolysaccharide and lipoteichoic acid treatment in human gingival fibroblasts","volume":"35","author":"Gutierrez\u2010Venegas","year":"2011","journal-title":"Cell Biol. Int."},{"key":"10.1016\/j.ejphar.2025.177873_bib11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1177\/0023677215570087","article-title":"Lipopolysaccharide-induced inflammatory liver injury in mice","volume":"49","author":"Hamesch","year":"2015","journal-title":"Lab. Anim."},{"key":"10.1016\/j.ejphar.2025.177873_bib12","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.biopha.2018.06.125","article-title":"Role of PI3K\/Akt\/NF-\u03baB and GSK-3\u03b2 pathways in the rat model of cardiopulmonary bypass-related lung injury","volume":"106","author":"He","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejphar.2025.177873_bib13","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1007\/s12192-023-01391-4","article-title":"Wogonin attenuates inflammation and oxidative stress in lipopolysaccharide-induced mastitis by inhibiting Akt\/NF-\u03baB pathway and activating the Nrf2\/HO-1 signaling","volume":"28","author":"He","year":"2023","journal-title":"Cell Stress Chaperones."},{"key":"10.1016\/j.ejphar.2025.177873_bib14","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/jpp\/rgab170","article-title":"Rupatadine ameliorated ulcerative colitis in rats via modulation of platelet-activatiweng factor\/interleukin-6\/vascular endothelial growth factor signalling pathway","volume":"74","author":"Ibrahim","year":"2022","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177873_bib15","doi-asserted-by":"crossref","first-page":"40190","DOI":"10.1007\/s11356-022-18899-4","article-title":"Role of Platelet-activating factor and HO-1 in mediating the protective effect of rupatadine against 5-fluorouracil-induced hepatotoxicity in rats","volume":"29","author":"Khalaf","year":"2022","journal-title":"Environ. Sci. Pollut. Control Ser."},{"key":"10.1016\/j.ejphar.2025.177873_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.118750","article-title":"Lauric acid ameliorates lipopolysaccharide (LPS)-induced liver inflammation by mediating TLR4\/MyD88 pathway in Sprague Dawley (SD) rats","volume":"265","author":"Khan","year":"2021","journal-title":"Life Sci."},{"key":"10.1016\/j.ejphar.2025.177873_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10753-016-0447-7","article-title":"Indirubin inhibits LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways","volume":"40","author":"Lai","year":"2017","journal-title":"Inflammation."},{"key":"10.1016\/j.ejphar.2025.177873_bib18","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.intimp.2017.08.009","article-title":"Preventive effects of interleukin-6 in lipopolysaccharide\/d-galactosamine induced acute liver injury via regulating inflammatory response in hepatic macrophages","volume":"51","author":"Li","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejphar.2025.177873_bib19","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/949157","article-title":"Innate immune cells in liver inflammation","volume":"2012","author":"Liaskou","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.ejphar.2025.177873_bib20","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1038\/s41418-020-0536-x","article-title":"HSPA12A attenuates lipopolysaccharide-induced liver injury through inhibiting caspase-11-mediated hepatocyte pyroptosis via PGC-1\u03b1-dependent acyloxyacyl hydrolase expression","volume":"27","author":"Liu","year":"2020","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.ejphar.2025.177873_bib21","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine."},{"key":"10.1016\/j.ejphar.2025.177873_bib22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0068631","article-title":"Rupatadine protects against pulmonary fibrosis by attenuating PAF-mediated senescence in rodents","volume":"8","author":"Lv","year":"2013","journal-title":"PLoS One."},{"key":"10.1016\/j.ejphar.2025.177873_bib23","article-title":"Research progress on rodent models and its mechanisms of liver injury","author":"Mao","year":"2023","journal-title":"Life Sci."},{"key":"10.1016\/j.ejphar.2025.177873_bib24","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1139\/cjpp-2021-0330","article-title":"Therapeutic effect of rupatadine against l-arginine-induced acute pancreatitis in rats: role of inflammation","volume":"100","author":"Mohamed","year":"2022","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177873_bib25","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.ejphar.2025.177873_bib26","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.intimp.2017.09.022","article-title":"Hepatoprotective effect of quercetin against LPS\/d-GalN induced acute liver injury in mice by inhibiting the IKK\/NF-\u03baB and MAPK signal pathways","volume":"52","author":"Peng","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejphar.2025.177873_bib27","article-title":"Micheliolide inhibits LPS-induced inflammatory response and protects mice from LPS challenge","volume":"6","author":"Qin","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2025.177873_bib28","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1203\/01.pdr.0000252437.51779.21","article-title":"Lipopolysaccharide exposure modifies high tidal volume ventilation-induced proinflammatory mediator expression in newborn rat lungs","volume":"61","author":"Roth-Kleiner","year":"2007","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.ejphar.2025.177873_bib29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.intimp.2018.03.033","article-title":"Protective effect of pristimerin against LPS-induced acute lung injury in mice","volume":"59","author":"Shaaban","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejphar.2025.177873_bib30","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.12659\/MSM.914114","article-title":"Allicin improves lung injury induced by sepsis via regulation of the toll-like receptor 4 (TLR4)\/myeloid differentiation primary response 88 (MYD88)\/nuclear factor kappa B (NF-\u03baB) pathway","volume":"25","author":"Shen","year":"2019","journal-title":"Med. Sci. Monit.: Int. Med. J. Exp. Clin. Res."},{"key":"10.1016\/j.ejphar.2025.177873_bib31","first-page":"4529","article-title":"Research progress on the PI3K\/AKT signaling pathway in gynecological cancer","volume":"19","author":"Shi","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.ejphar.2025.177873_bib32","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/j.1365-2567.2004.01946.x","article-title":"Histamine induces Toll\u2010like receptor 2 and 4 expression in endothelial cells and enhances sensitivity to gram\u2010positive and gram\u2010negative bacterial cell wall components","volume":"113","author":"Talreja","year":"2004","journal-title":"Immunology."},{"key":"10.1016\/j.ejphar.2025.177873_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2020.107272","article-title":"Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4\/NF-kB signaling pathway","volume":"91","author":"Tang","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejphar.2025.177873_bib34","article-title":"Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4\/NF-\u03baBp65\/MAPKs signaling cascade","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2025.177873_bib35","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.797096","article-title":"Paramylon from Euglena gracilis prevents lipopolysaccharide-induced acute liver injury","volume":"12","author":"Xie","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejphar.2025.177873_bib36","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.biopha.2017.11.083","article-title":"Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation","volume":"96","author":"Xiong","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejphar.2025.177873_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2021.114863","article-title":"Maresin 1 protects against lipopolysaccharide\/d-galactosamine-induced acute liver injury by inhibiting macrophage pyroptosis and inflammatory response","volume":"195","author":"Yang","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177873_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2021.107798","article-title":"Lipopolysaccharide\/D-galactosamine-induced acute liver injury could be attenuated by dopamine receptor agonist rotigotine via regulating NF-\u03baB signaling pathway","volume":"96","author":"Yue","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejphar.2025.177873_bib39","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/8877056","article-title":"Tofacitinib ameliorates lipopolysaccharide\u2010induced acute kidney injury by blocking the JAK\u2010STAT1\/STAT3 signaling pathway","volume":"2021","author":"Yun","year":"2021","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.ejphar.2025.177873_bib40","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s10753-017-0659-5","article-title":"A novel role of a chemotherapeutic agent in a rat model of endotoxemia: modulation of the STAT-3 signaling pathway","volume":"41","author":"Zaki","year":"2018","journal-title":"Inflammation."},{"key":"10.1016\/j.ejphar.2025.177873_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114291","article-title":"Toll-like receptor 4 (TLR4) inhibitors: current research and prospective","volume":"235","author":"Zhang","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejphar.2025.177873_bib42","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/s41418-019-0412-8","article-title":"Histone methyltransferase G9a protects against acute liver injury through GSTP1","volume":"27","author":"Zhang","year":"2020","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.ejphar.2025.177873_bib43","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.ijbiomac.2020.06.266","article-title":"A novel polysaccharide from Acorus tatarinowii protects against LPS-induced neuroinflammation and neurotoxicity by inhibiting TLR4-mediated MyD88\/NF-\u03baB and PI3K\/Akt signaling pathways","volume":"163","author":"Zhong","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.ejphar.2025.177873_bib44","doi-asserted-by":"crossref","DOI":"10.1016\/j.jff.2021.104456","article-title":"Phillygenin protects against osteoarthritis by repressing inflammation via PI3K\/Akt\/NF-\u03baB signaling: in vitro and vivo studies","volume":"80","author":"Zhou","year":"2021","journal-title":"J. Funct.Foods."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925006272?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925006272?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:26:36Z","timestamp":1778876796000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299925006272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":44,"alternative-id":["S0014299925006272"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.177873","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Rupatadine modulates TLR4\/MYD88\/NF-\u03baB and AKT\/PI3K signaling pathways, attenuating sepsis-induced liver injury in mice","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.177873","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"177873"}}