Apocynin suppresses the generation of
reactive oxygen species (ROS) that are implicated in
ischemia-reperfusion (I/R)
lung injury. We thus hypothesized that
apocynin attenuates I/R. Furthermore, we explored the mechanisms by which
apocynin may attenuate I/R. I/R was induced in an isolated and perfused rat lung model with
ischemia for 1 h followed by reperfusion for 1 h.
Apocynin was administered in the circulating perfusate at the onset of
ischemia. Hemodynamics,
lung injury indices, inflammatory responses, and activation of apoptotic pathways were determined. An increase in lung permeability and lung
weight gain was noted after I/R. Peak airway pressure was increased, and pH of circulating perfusate was decreased. The adhesion molecule of neutrophil (CD31) in perfusate was upregulated. The levels of
albumin, white blood cell count, and inflammatory
cytokines including interleukin-1β,
tumor necrosis factor-α, and macrophage inflammatory protein-2 increased in lung lavage fluid; the concentrations of carbonyl and
thiobarbituric acid reactive substances were greater in the circulating perfusate; and the expression of
myeloperoxidase, JNK, P38, and
caspase-3 in lung tissue was greater in the control group. Upregulation and activation of nuclear factor-κB (NF-κB) in nuclei were found in I/R. The administration of
apocynin attenuated these inflammatory responses and lung permeability associated with decreased activation of NF-κB. We conclude that I/R is associated with inflammatory responses including the generation of ROS, adhesion
protein of neutrophil,
cytokines, and the activation of
mitogen-activated protein kinase and NF-κB cascade. The administration of
apocynin attenuates the inflammatory responses and I/R in the isolated, perfused rat lung model.