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This study aimed to reduce early adhesion formation by using the protease inhibitors, nafamostat mesylate (NFM), UAMC-00050, enoxaparin, and GM6001, in the cecal ligation and puncture (CLP) model and the ischemic button (IB) model in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice subjected to CLP received NFM (1, 10, or 20\u00a0mg\/kg), UAMC-00050 (1 or 5\u00a0mg\/kg), enoxaparin (1, 5, or 10\u00a0mg\/kg), or GM6001 (100\u00a0mg\/kg) in preventive, delayed, and combined setups. Adhesion severity was assessed 48\u00a0h post-CLP based on the extent, tenacity, and surgical access time. NFM and enoxaparin were tested further for 7 days in the IB model. Protease activity and gene expression were analyzed in NFM-treated mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CLP induced adhesions more strongly than the sham procedure. Preventive NFM reduced the adhesion extent by 49.8%. Repeated enoxaparin administration reduced the extent, tenacity, and access time (-46%). UAMC-00050 and GM6001 had no effect. In the IB model, enoxaparin, but not NFM, reduced the adhesion surface area and tenacity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Enoxaparin and NFM reduced adhesions effectively, suggesting that coagulation inhibition plays a key role. These findings suggest that selective protease inhibitors, when administered in a timely manner, could reduce intraperitoneal adhesions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00595-025-03166-z","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T15:12:26Z","timestamp":1763133146000},"page":"673-689","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Using protease inhibitors to prevent intraperitoneal adhesions: effects of nafamostat mesylate, UAMC-00050, GM6001, and enoxaparin in the cecal ligation and puncture model and the ischemic button model"],"prefix":"10.1007","volume":"56","author":[{"given":"Philip","family":"Plaeke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joris","family":"De Man","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gun-Soo","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"de Bruyn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"De Meester","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe G","family":"Jorens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koen","family":"Augustyns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg C","family":"Kalff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Wehner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Hubens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedicte","family":"De Winter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"issue":"2","key":"3166_CR1","doi-asserted-by":"publisher","first-page":"e104","DOI":"10.1016\/j.jviscsurg.2011.11.006","volume":"149","author":"M Oua\u00efssi","year":"2012","unstructured":"Oua\u00efssi M, Gaujoux S, Veyrie N, Den\u00e8ve E, Brigand C, Castel B, et al. 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