Effect of NG-nitro-L-arginine methyl ester on intestinal permeability following intestinal ischemia-reperfusion injury in a rat model

Chih Cheng Luo, Han Ming Chen, Cheng Hsun Chiu, Jer Nan Lin, Jeng Chang Chen

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Abstract

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200-300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early N(G)-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI.

Original languageEnglish
Pages (from-to)60-63
Number of pages4
JournalBiology of the Neonate
Volume80
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

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Keywords

  • Ischemia-reperfusion injury
  • Nitric oxide synthesis inhibitor
  • Small intestine

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health

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