Endotoxin causes hydrogen peroxide-induced lung lipid peroxidation and prostanoid production
R. Demling, C. Lalonde, A. Seekamp and N. Fiore
Longwood Area Trauma Center, Brigham and Women's hospital, Boston, MA.
We studied the role of hydrogen peroxide release on endotoxin-induced lung
injury in unanesthetized sheep with chronic lung lymph fistulas. We also
further defined the relationship between endotoxin injury, lipid
peroxidation, and prostaglandin production. Sheep were given endotoxin
alone (1 microgram/kg) or pretreated with catalase (32,500 U/kg) or
ibuprofen (12.5 mg/kg). Endotoxin alone resulted in an early prostanoid
release, lipid peroxidation measured as circulating conjugated dienes both
one and four hours after the administration of endotoxin, pulmonary
hypertension, hypoxia, and increased protein permeability. Permeability was
monitored by lymph flow and lymph protein content. Catalase pretreatment
significantly attenuated all of these aspects of the endotoxin response.
Ibuprofen prevented the early lung changes and blocked prostanoid release
but did not attenuate the increased permeability. In addition,
cyclo-oxygenase inhibition had a dual effect on lipid peroxidation,
increasing initial conjugated diene levels while suppressing the later
release. The initial effect was clearly related to cyclo-oxygenase
blockade. The early conjugated diene release appears to be related to
arachidonic acid metabolism and does not correspond to the degree of
increased permeability. We conclude that H2O2 plays a major role in lung
injury after endotoxin.
