Desferrioxamine attenuates minor lung injury following surgical acute liver failure

¹ 2^nd Dept of Anesthesiology
² 2^nd Dept of Surgery
³ Dept of Pathology, University of Athens School of Medicine, Aretaieion Hospital, Athens, Greece
⁴ 2^nd Dept of Internal Medicine, University of Athens School of Medicine, Attikon Hospital, Athens, Greece.
⁵ 1^st Dept of Critical Care, University of Athens School of Medicine, Evangelismos Hospital, Athens, Greece
⁶ Dept of Biochemistry
⁷ Dept of Critical Care, University of Ioannina, University Hospital, Ioannina, Greece

^* To whom correspondence should be addressed. E-mail: gnakos{at}cc.uoi.gr.

	Abstract

Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study is to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF.

Fourteen adult female domestic pigs were subjected to surgical devascularization of the liver and were randomized to a study group (DFX group, n=7), which received postoperative intravenous infusion of desferrioxamine (14.5 mg·kg^-1·h^-1 for the first 6h postoperatively and 2.4 mg·kg^-1·h^-1 until completion of 24h), and a control group (n=7). Postoperative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis.

Desferrioxamine resulted in reduced BALF protein levels and tissue phospholipase A₂ (PLA₂) activity. Plasma malondialdehyde and BALF nitrates + nitrites concentrations were lower, while catalase activity in the lung was higher after DFX treatment. Phospholipase A₂, platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocytes necrosis and total lung injury in the DFX-treated animals.

Desferrioxamine reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA₂ and the attenuation of pneumonocytes necrosis could represent beneficial mechanisms by which DFX improves alveolar-capillary membrane permeability and alveolar spaces collapse.