{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T12:15:33Z","timestamp":1776341733058,"version":"3.51.2"},"reference-count":67,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to investigate the protective effects of fenofibrate against sepsis-induced acute lung injury using a feces-induced peritonitis (FIP) rat model, with particular emphasis on the modulation of HSP70 and Nrf2 as key cellular defense mechanisms. The FIP model was employed to mimic colon-origin abdominal sepsis, frequently encountered in general surgery, including conditions such as colonic perforation and anastomotic leakage. Thirty male Wistar albino rats were randomly assigned to control, FIP, and FIP + fenofibrate groups. Sepsis was induced by intraperitoneal injection of a fecal-saline suspension. Fenofibrate (100 mg\/kg) was administered intraperitoneally after the FIP procedure. After 24 h, lung tissues and blood samples were collected. Assessments included histopathology (H&amp;E staining), thoracic CT imaging, arterial blood gas analysis, ELISA-based quantification of plasma cytokines (IL-6, IL-1\u03b2, TNF-\u03b1), MDA for oxidative stress, and lung tissue levels of HSP70 and Nrf2. Feces-induced peritonitis caused severe acute lung injury, evidenced by increased histopathological damage (p &lt; 0.001), impaired gas exchange (PaO2 and PaCO2, p &lt; 0.01), elevated inflammatory cytokines (IL-6, IL-1\u03b2, TNF-\u03b1; p &lt; 0.001), increased oxidative stress (MDA, p &lt; 0.001), and suppressed lung Nrf2 and HSP70 expression (p &lt; 0.001). Fenofibrate significantly attenuated lung injury, improved gas exchange (p &lt; 0.05), reduced inflammation (p &lt; 0.01\u2013p &lt; 0.001), decreased MDA (p &lt; 0.001), and increased Nrf2 (p &lt; 0.001) and HSP70 (p &lt; 0.01). Fenofibrate attenuates sepsis-induced acute lung injury by reducing inflammation and oxidative stress while preserving HSP-70 and Nrf2-mediated cytoprotective pathways. These findings are clinically relevant to general surgery, as septic lung injury commonly arises from colon-origin abdominal sepsis, including colonic perforation and anastomotic leakage.<\/jats:p>","DOI":"10.3390\/ijms27083556","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:35:42Z","timestamp":1776339342000},"page":"3556","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fenofibrate Mitigates Acute Lung Injury in a Rat Model of Feces-Induced Peritonitis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-4919","authenticated-orcid":false,"given":"Ahmet","family":"Akba\u015f","sequence":"first","affiliation":[{"name":"Department of General Surgery, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1358-0158","authenticated-orcid":false,"given":"Mehmet Fatih","family":"Dasiran","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Faculty of Medicine, Tokat Gaziosmanpasa University, 60250 Tokat, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2289-5514","authenticated-orcid":false,"given":"Hassen","family":"Daghmoura","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Faculty of Medicine, Bezmialem Vakif University, 34093 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2480-1374","authenticated-orcid":false,"given":"Bakiye","family":"Akba\u015f","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4272-0562","authenticated-orcid":false,"given":"Hatice","family":"Aygun","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory, BAMER, Biruni University, 34010 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6893-2419","authenticated-orcid":false,"given":"Ahmet","family":"Serdaroglu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-0522","authenticated-orcid":false,"given":"Yi\u011fit","family":"Uyanikgil","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Ege University, 35100 Izmir, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-9298","authenticated-orcid":false,"given":"G\u00fcl\u00e7in","family":"Ercan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, Istanbul Provincial Directorate of Health, 34668 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5427-8428","authenticated-orcid":false,"given":"Oytun","family":"Erbas","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, BAMER, Biruni University, 34010 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries","volume":"315","author":"Bellani","year":"2016","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","article-title":"Acute respiratory distress syndrome","volume":"5","author":"Matthay","year":"2019","journal-title":"Nat. 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