Antioxidant treatment attenuates intestinal mucosal damage and gut barrier dysfunction after major hepatectomy. Study in a porcine model.

摘要

BACKGROUND: This study aims to evaluate whether injury of gut mucosa in a porcine model of post-hepatectomy liver dysfunction can be prevented using antioxidant treatment with desferrioxamine. METHODS: Post-hepatectomy liver failure was induced in pigs combining major (70%) liver resection and ischemia/reperfusion injury. An ischemic period of 150 minutes, was followed by reperfusion for 24 h. Animals were randomly divided into a control group (n = 6) and a desferrioxamine group (DFX, n = 6). DFX animals were treated with continuous IV infusion of desferrioxamine 100 mg/kg. Intestinal mucosal injury (IMI), bacterial and endotoxin translocation (BT) were evaluated in all animals. Intestinal mucosa was also evaluated for oxidative markers. RESULTS: DFX animals had significantly lower IMI score (3.3 +/- 1.2 vs. 1.8 +/- 0.9, p < 0.05), decreased BT in the portal circulation at 0 and 12 h of reperfusion (p = 0.007 and p = 0.008, respectively), decreased portal endotoxin levels at 6 (p = 0.006) and 24 h (p = 0.004), decreased systemic endotoxin levels (p = 0.01) at 24 h compared to controls. Also, 24 h post-reperfusion mucosal malondialdehyde and protein carbonyls were decreased in DFX animals compared to controls (4.1 +/- 1.2 vs. 2.5 +/- 1.2, p = 0.05 and 0.5 +/- 0.1 vs. 0.4 +/- 0.1, p = 0.04 respectively). CONCLUSION: Desferrioxamine seems to attenuate mucosal injury from post-hepatectomy liver dysfunction possibly through blockage of iron-catalyzed oxidative reactions.