Iron chelation prevents lung injury after major hepatectomy.

Abstract

AIM:

Oxidative stress has been implicated in lung injury following ischemia/reperfusion and resection of the liver. We tested whether alleviating oxidative stress with iron chelation could improve lung injury after extended hepatectomy.

METHODS:

Twelve adult female pigs subjected to liver ischemia for 150 min, 65-70% hepatectomy and reperfusion of the remnant liver for 24 h were randomized to a desferrioxamine (DF) group (n = 6) which received i.v. desferrioxamine to a total dose of 100 mg/kg during both ischemia and reperfusion, and a control (C) group (n = 6). We recorded hemodynamic and respiratory parameters, plasma interleukin-6 and malondialdehyde levels, as well as liver malondialdehyde and protein carbonyls content. Total non-heme iron was measured in lung and liver. Pulmonary tissue was evaluated histologically for its nitrotyrosine and protein carbonyls content and for superoxide dismutase (SOD) and platelet-activating factor acetylhydrolase (PAF-AcH) activities.

RESULTS:

Reperfusion of the remnant liver resulted in gradual deterioration of gas-exchange and pulmonary vascular abnormalities. Iron chelation significantly decreased the oxidative markers in plasma, liver and the lung and lowered activities of pulmonary SOD and PAF-AcH. The improved liver function was followed by improved arterial oxygenation and pulmonary vascular resistance. DF also improved alveolar collapse and inflammatory cell infiltration, while serum interleukin-6 increased.

CONCLUSION:

In an experimental pig model that combines liver resection with prolonged ischemia, iron chelation during reperfusion of the remnant liver is associated with improvement of several parameters of oxidative stress, lung injury and arterial oxygenation.

• Authors: Konstantinos Kalimeris, Constantinos Nastos, Nikolaos Papoutsidakis, Marianna N Xanthopoulou, George Defterevos, Aliki Tympa, Agatha Pafiti, Ioanna Andreadou, Georgia Kostopanagiotou, Vassilios Smyrniotis, Nikolaos Arkadopoulos
• Journal: Hepatology research : the official journal of the Japan Society of Hepatology (Hepatol Res) Vol. 40 Issue 8 Pg. 841-50 (Aug 2010) ISSN: 1872-034X [Electronic] Netherlands
• PMID: 20649822 (Publication Type: Journal Article)