OxyFile #229
Endotoxin-induced hydrogen peroxide production in intact
pulmonary circulation of rat.
Author: Minamiya Y; Abo S; Kitamura M; Izumi K; Kimura Y;
Tozawa K; Saito S
Source: Am J Respir Crit Care Med 1995 Jul; 152(1):348-54
Abstract:
Although the importance of free oxygen radical has been
reported in acute lung injury, the direct evidence in vivo
model was lacking. We report a new method, which for the
first time allows direct detection of hydrogen peroxide
in the intact rat pulmonary microcirculation. We used the
computer image-analyzing system and 2',7'-dichlorofluorescin
diacetate for the marker of hydrogen peroxide production
in vivo. A rat sepsis model was produced by continuous
infusion of endotoxin for 30, 60, and 120 min. Hydrogen
peroxide production in the pulmonary microcirculation of
the sepsis rat was higher than in the control rat at each
time point (p < 0.01) and increased time-dependently (p
< 0.01). Catalase (5,000 U/kg) almost completely inhibited
the hydrogen peroxide production in the sepsis rat (p <
0.01). In high-power view, hydrogen peroxide was detected
in granulocytes that adhered to the capillaries and endothelial
cells that were adjoining adherent granulocytes. These
observations suggest that hydrogen peroxide in the endothelium
was diffused from granulocytes. In this study, we demonstrated
direct evidence of hydrogen peroxide production from adherent
granulocytes in intact rat lung treated with endotoxin.
We conclude that endotoxin causes the granulocyte adhesion
and oxidative stress to the endothelium due to adherent
granulocytes within 30 min in the pulmonary microcirculation.