{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:09:35Z","timestamp":1780510175038,"version":"3.54.1"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Sepsis is a life-threatening condition characterized by a dysregulated immune response leading to multiple organ dysfunction. Despite the use of antibiotics and anti-inflammatory drugs, recovery remains limited. Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, is widely used to mimic sepsis-like conditions in animals. This study investigated the anti-inflammatory and protective effects of Roflumilast at two doses (1.5 and 3 mg\/kg) in a single-dose LPS-induced sepsis model. Sepsis was induced in rats by intraperitoneal injection of LPS (30 mg\/kg), and Roflumilast was administered for 10 days. Liver and kidney injury were evaluated by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels. Pro-inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 beta (IL-1\u03b2), and interleukin-6 (IL-6), were measured using ELISA. Histopathological damage and kidney injury molecule-1 (KIM-1) expression were assessed in major organs. LPS significantly increased biochemical and cytokine markers, causing severe tissue damage. While 1.5 mg\/kg Roflumilast showed no protective effects, 3 mg\/kg markedly reduced inflammatory and injury markers, improved tissue architecture, and decreased KIM-1 expression. These findings suggest that a higher dose of Roflumilast effectively mitigates LPS-induced systemic inflammation and organ injury, supporting its potential as a therapeutic option for sepsis.<\/jats:p>","DOI":"10.1371\/journal.pone.0350653","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:27:43Z","timestamp":1780507663000},"page":"e0350653","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Roflumilast prevented tissue damage caused by lipopolysaccharide-induced sepsis via anti-inflammatory action"],"prefix":"10.1371","volume":"21","author":[{"given":"Demet","family":"Yal\u00e7\u0131n Kehribar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4387-6929","authenticated-orcid":true,"given":"Lale","family":"Saka 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