Eicosapentaenoic acid reduces pulmonary edema in endotoxemic rats

Background. Recently, eicosapentaenoic acid (EPA) was found to have an anti-inflammatory effect attributable to diminished synthesis of arachidonic acid metabolites that initiate acute lung injury, We evaluated the ability of dietary EPA supplementation to prevent endotoxin-induced acute lung injury in rats. Materials and methods. Rats fed a standard diet were divided randomly into two groups: for 2 weeks one group additionally was fed 1000 mg/kg/day of EPA ethyl ester emulsion (EPA rats), while in the other group the diet was supplemented with vehicle alone (control rats). Fatty acid components of alveolar macrophages (ARI) were measured, as well as leukotriene (LT) B-4 and LTB5 production by AM exposed in vitro to calcium ionophore A23187. Plasma concentrations of thromboxane (Tx) B-2, a stable metabolite of TxA(2), were examined 1 h after inducing lung injury with endotoxin (2 mg/kg iv). At 6 h, wet/dry (W/D) weight ratios were calculated for the lungs to assess pulmonary edema, and neutrophils were counted in pulmonary parenchyma and peripheral blood. Results. Arachidonic acid content and LTB4 generation in AM were significantly lower in EPA rats than in controls; conversely, EPA content and LTB5 generation in AM were significantly higher in the EPA group. Neutrophil counts in lung parenchyma and peripheral blood did not differ between groups, but W/D and plasma TxB(2) concentrations were significantly lower in EPA rats. Conclusions. EPA supplementation depressed arachidonic acid content and LTB4 generation in AM and plasma TxB(2) in our model, leading to decreased pulmonary edema. (C) 2000 Academic Press.