Lipid peroxidation and acute lung injury after thermal trauma to skin. Evidence of a role for hydroxyl radical.
The authors have previously shown that thermal injury to the skin of rats results in the development of acute lung injury that is susceptible to systemic treatment of animals with catalase and dependent on the presence of neutrophils. The current studies have been expanded for exploration of the nature of the neutrophil-derived oxygen products responsible for the lung injury and have also focused on evidence of the appearance of products of lipid peroxidation (conjugated dienes). With respect to the former, treatment of rats with iron chelators (deferoxamine mesylate, 2,3-dihydroxybenzoic acid), with scavengers of hydroxyl radical (dimethyl sulfoxide, dimethyl thiourea, sodium benzoate), or with vitamin E affords a significant degree of protection from acute lung injury as assessed by changes in lung vascular permeability and by morphologic parameters. These data suggest that lung vascular injury after thermal trauma of the skin is related to the generation by neutrophils of the hydroxyl radical. Conjugated dienes have been demonstrated to appear sequentially both in the burned skin (at 1/4 hour) and in the lungs (at 2 hours), as well as in the plasma (with peaks at 1/2 and at 3 hours) after thermal injury. The appearance of the conjugated dienes in plasma at the two intervals of time is greatly diminished if animals are pretreated with the iron chelator deferoxamine, with catalase, or with scavengers of hydroxyl radical. Furthermore, the appearance of conjugated dienes in plasma at 30 minutes and 3 hours is significantly diminished if animals are depleted of neutrophils, complement-depleted, or the burned skin is excised immediately after thermal injury. These data indicate a linkage between thermal trauma of skin, secondary injury of lung, and appearance in plasma and tissues of products of lipid peroxidation.
Till
G O
GO
Hatherill
J R
JR
Tourtellotte
W W
WW
Lutz
M J
MJ
Ward
P A
PA
D000818:Animals; D002056:Burns / Q000150:complications*; D002199:Capillary Permeability / Q000187:drug effects; D002614:Chelating Agents / Q000627:therapeutic use; D003676:Deferoxamine / Q000627:therapeutic use; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use; D006878:Hydroxides / Q000502:physiology*; D062385:Hydroxybenzoates / Q000627:therapeutic use; D017665:Hydroxyl Radical; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D008168:Lung / Q000648:ultrastructure; D008171:Lung Diseases / Q000209:etiology* / Q000517:prevention & control; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000293:injuries*; D014810:Vitamin E / Q000627:therapeutic use
D002614:Chelating Agents; D006878:Hydroxides; D062385:Hydroxybenzoates; D008054:Lipid Peroxides; D014810:Vitamin E; D017665:Hydroxyl Radical; D003676:Deferoxamine; D004121:Dimethyl Sulfoxide