Background. Recently, eicosapentaenoic acid (EPA) was found to have an anti
-inflammatory effect attributable to diminished synthesis of arachidonic ac
id 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 EP
A ethyl ester emulsion (EPA rats), while in the other group the diet was su
pplemented with vehicle alone (control rats). Fatty acid components of alve
olar macrophages (ARI) were measured, as well as leukotriene (LT) B-4 and L
TB5 production by AM exposed in vitro to calcium ionophore A23187. Plasma c
oncentrations 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 pulmo
nary edema, and neutrophils were counted in pulmonary parenchyma and periph
eral blood.
Results. Arachidonic acid content and LTB4 generation in AM were significan
tly lower in EPA rats than in controls; conversely, EPA content and LTB5 ge
neration in AM were significantly higher in the EPA group. Neutrophil count
s in lung parenchyma and peripheral blood did not differ between groups, bu
t W/D and plasma TxB(2) concentrations were significantly lower in EPA rats
.
Conclusions. EPA supplementation depressed arachidonic acid content and LTB
4 generation in AM and plasma TxB(2) in our model, leading to decreased pul
monary edema. (C) 2000 Academic Press.