{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:57:50Z","timestamp":1772999870936,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020410","name":"T\u00fcrkiye Sa\u011fl\u0131k Enstit\u00fcleri Ba\u015fkanl\u0131\u011f\u0131","doi-asserted-by":"publisher","award":["31183"],"award-info":[{"award-number":["31183"]}],"id":[{"id":"10.13039\/100020410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis is a life\u2010threatening organ dysfunction caused by a dysregulated host response to infection, characterised by excessive oxidative stress and cytokine release. This study evaluated the protective effects of avasopasem manganese (AVA), a superoxide dismutase mimetic, on sepsis\u2010induced lung injury in a murine model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sepsis was induced in mice via cecal ligation and puncture (CLP). The study included five groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098\/group): Sham (control), CLP (Sepsis) and CLP\u2009+\u2009AVA at doses of 2.5, 5 or 10\u2009mg\/kg. Serum and lung tissue samples were analysed for pro\u2010inflammatory cytokines (tumour necrosis factor \u03b1 (TNF\u2010\u03b1), interleukin (IL)\u20101\u03b2, IL\u20106), oxidative stress markers (malondialdehyde, MDA) and antioxidant enzyme activity (superoxide dismutase, SOD; glutathione, GSH; catalase, CAT). Quantitative real\u2010time PCR (qRT\u2010PCR) assessed cytokine mRNA expression, while histopathological examination evaluated lung tissue damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum and lung tissue levels of TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20106 and MDA were lowest in the healthy control group and highest in the sepsis group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001). A significant dose\u2010dependent decrease in cytokine levels was observed with increasing doses of AVA. Regarding antioxidants, SOD, GSH and CAT enzyme activities were highest in the control group and lowest in the sepsis group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05). A significant increase in antioxidant enzyme activity was observed with increasing doses of AVA. In molecular analyses, the expression levels of TNF\u2010\u03b1, IL\u20101\u03b2 and IL\u20106 were highest in the sepsis group, while relative messenger RNA (mRNA) expression results changed inversely with the drug dosage. Histopathological analyses revealed inflammation, edema and hyaline membrane formation in the sepsis group, whereas increasing doses of the drug showed improvement in lung tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AVA demonstrated a significant protective effect against sepsis\u2010induced lung injury through its antioxidant and anti\u2010inflammatory properties. The most effective dose was determined to be 10\u2009mg\/kg. These findings suggest the potential use of AVA as an adjunctive agent in sepsis treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70111","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T14:30:48Z","timestamp":1755613848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective effects of avasopasem manganese (GC4419) against sepsis\u2010induced acute lung injury: A comprehensive experimental study"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4658-5254","authenticated-orcid":false,"given":"R.","family":"Peks\u00f6z","sequence":"first","affiliation":[{"name":"Department of General Surgery Atat\u00fcrk University Research Hospital  Erzurum Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0289-1252","authenticated-orcid":false,"given":"E.","family":"A\u011f\u0131rman","sequence":"additional","affiliation":[{"name":"Department of General Surgery Erzurum City Hospital  Erzurum Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-8317","authenticated-orcid":false,"given":"T.","family":"Tavac\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology Sakarya University Faculty of Medicine  Sakarya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4683-0648","authenticated-orcid":false,"given":"A. 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