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

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.