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

Abstract

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.

• Authors: Constantinos Nastos, Konstantinos Kalimeris, Nikolaos Papoutsidakis, George Defterevos, Agathi Pafiti, Helen Kalogeropoulou, Loukia Zerva, Tzortzis Nomikos, Georgia Kostopanagiotou, Vasillios Smyrniotis, Nikolaos Arkadopoulos
• Journal: Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract (J Gastrointest Surg) Vol. 15 Issue 5 Pg. 809-17 (May 2011) ISSN: 1873-4626 [Electronic] United States
• PMID: 21380631 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Siderophores
• Deferoxamine

Topics

• Animals
• Antioxidants (administration & dosage, pharmacokinetics)
• Deferoxamine (administration & dosage, pharmacokinetics)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Follow-Up Studies
• Hepatectomy (adverse effects)
• Infusions, Intravenous
• Intestinal Mucosa (drug effects, metabolism, pathology)
• Permeability (drug effects)
• Reperfusion Injury (drug therapy, etiology, metabolism)
• Siderophores (administration & dosage, pharmacokinetics)
• Swine
• Treatment Outcome