Nonselective matrix metalloproteinase but not tumor necrosis factor-α inhibition effectively preserves the early critical colon anastomotic integrity

Magnus S Agren, Thomas Levin Andersen, Line Andersen, Christine Bruun Schiødt, Vikas Surve, Troels T Andreassen, Juha Risteli, Lennart E Franzén, Jean-Marie Delaissé, Anne-Marie Heegaard, Lars N Jorgensen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: Increased matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of colorectal anastomotic leakage. Tumor necrosis factor-α (TNF-α) induces MMPs and may influence anastomosis repair. METHODS: We assessed the efficacies of the nonselective hydroxamate MMP inhibitor GM6001, the selective hydroxamate MMP inhibitor AG3340 and a TNF-α antagonist with respect to anastomotic breaking strength of left-sided colon anastomoses in male Sprague-Dawley rats. RESULTS: Systemic GM6001 treatment effectively blocked MMP activity and maintained the initial breaking strength day 0 of the anastomoses when administered subcutaneously as daily depositions (100 mg/kg) or continuously (10 mg/kg/day). In contrast, the anastomotic biomechanic strength was lowered by 55% (p 
Original languageEnglish
JournalInternational Journal of Colorectal Disease
Volume26
Issue number3
Pages (from-to)329-337
ISSN0179-1958
DOIs
Publication statusPublished - 2011

Fingerprint Dive into the research topics of 'Nonselective matrix metalloproteinase but not tumor necrosis factor-α inhibition effectively preserves the early critical colon anastomotic integrity'. Together they form a unique fingerprint.

Cite this