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

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

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.

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Abbreviations

ROS:

Reactive oxygen species

RNS:

Reactive nitrate species

CVP:

Central venous pressure

MAP:

Mean arterial pressure

PP:

Portal pressure

MDA:

Malondialdehyde

CFU:

Colony forming units

IMI:

Intestinal mucosa injury

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Acknowledgments

We would like to thank D. Lavdas, S. Zournatzis and the quality control department of VIOSER A.E. for the sponsoring and measurement of endotoxin concentration in portal and systemic circulation.

Funding

This project was co-funded by the European Social Fund and National Resources—(EPEAEK II) PYTHAGORAS.

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Correspondence to Constantinos Nastos.

Additional information

Presented as an abstract in the International Surgical Week ISW 2009 in Adelaide.

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Nastos, C., Kalimeris, K., Papoutsidakis, N. et al. Antioxidant Treatment Attenuates Intestinal Mucosal Damage and Gut Barrier Dysfunction After Major Hepatectomy. Study in a Porcine Model. J Gastrointest Surg 15, 809–817 (2011). https://doi.org/10.1007/s11605-011-1475-0

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