Antioxidant Treatment Attenuates Intestinal Mucosal Damage and Gut Barrier Dysfunction After Major Hepatectomy. Study in a Porcine Model

Abstract

BackgroundThis 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. MethodsPost-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. ResultsDFX 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). ConclusionDesferrioxamine seems to attenuate mucosal injury from post-hepatectomy liver dysfunction possibly through blockage of iron-catalyzed oxidative reactions.