{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:14:43Z","timestamp":1792800883004,"version":"4.5.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ibuprofen overdose is commonly associated with gastrointestinal and renal toxicity; however, severe respiratory complications such as bronchial ulceration are rarely reported, and the underlying molecular mechanisms are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the potential molecular mechanisms of bronchial ulceration induced by an extreme ibuprofen overdose in a pediatric patient by integrating clinical observation with network toxicology-based computational predictions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We report a pediatric case of bronchial ulceration following a 360\u00a0mg\/kg ibuprofen overdose, supplemented by a systematic literature review. Network toxicology (shared target identification, PPI network, GO\/KEGG enrichment), molecular docking, and ADME prediction were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bronchoscopy on day 14 revealed multiple well-demarcated ulcers with pseudomembranes and markedly elevated IL-6 (1050.0\u00a0pg\/mL). Network toxicology identified 120 shared targets, with TNF-\u03b1, IL-6, and IL-1\u03b2 as hub genes. KEGG enrichment computationally predicted involvement of the IL-17 and AGE-RAGE pathways. Molecular docking confirmed strong binding affinities (&amp;lt;\u22125\u00a0kcal\/mol), while ADME predictions indicated high BBB permeability and DILI risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, extreme ibuprofen overdose can induce bronchial ulceration in children, as illustrated by this rare case. In silico predictions suggest that the toxic surge of free ibuprofen may perturb inflammatory homeostasis via potential off-target interactions, computationally implicating IL-17\/AGE-RAGE axes, leading to structural epithelial necrosis. While requiring further validation, this nuances classical paradigms and alerts clinicians to non-spasmodic airway injury in pediatric overdose.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1892875","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:29:29Z","timestamp":1789014569000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pediatric bronchial ulcers induced by ibuprofen overdose: a case report combined with network toxicology to decipher potential mechanisms"],"prefix":"10.3389","volume":"17","author":[{"given":"Yixuan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosheng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of PICU, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of PICU, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of PICU, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1055\/a-2465-3661","article-title":"The rare reason for massive lactic aciduria and mitochondrial disorders: combined oxidative phosphorylation deficiency type 23 (COXPD23)","volume":"229","author":"Akar","year":"2025","journal-title":"Z Geburtshilfe Neonatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"114147","DOI":"10.1016\/j.bcp.2020.114147","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective","volume":"180","author":"Bindu","year":"2020","journal-title":"Biochem. 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