Effective attenuation of endotoxin-induced acute lung injury by 2,3-diacetyloxybenzoic acid in two independent animal models.
The pathology of acute lung injury (ALI) is often modeled in animal studies by the administration of lipopolysaccharide (LPS), which results in an endotoxemia with sequelae similar to that seen in acute respiratory distress syndrome (ARDS). Here we report the results of two studies designed to examine the efficacy of a novel agent, 2,3-diacetyloxybenzoic acid (2,3-DABA), in the treatment of LPS-induced ALI. In two separate animal models, 2,3-DABA was effective in significantly reducing lung microvascular permeability, a condition commonly seen in ARDS, which results in pulmonary edema and respiratory insufficiency. In each model, it is demonstrated that the mechanism by which 2,3-DABA exerts this effect occurs subsequent to the recruitment of neutrophils to the site of inflammation. Lung permeability was significantly decreased in both models by treatment with 2,3-DABA, suggesting that this agent, either alone or in combination therapy, may be useful in the treatment of ALI associated with ARDS.
Eiznhamer
David A
DA
Advanced Life Sciences, Inc., 1440 Davey Road, Woodridge, IL 60517, USA. deiznhamer@advancedlifesciences.com
Flavin
Michael T
MT
Jesmok
Gary J
GJ
Borgia
Julian F
JF
Nelson
Deanna J
DJ
Burhop
Kenneth E
KE
Xu
Ze-Qi
ZQ
D000085:Acetates; D000818:Animals; D015824:Blood-Air Barrier / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004731:Endotoxins; D006168:Guinea Pigs; D062385:Hydroxybenzoates / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008168:Lung / Q000098:blood supply; D009504:Neutrophils / Q000473:pathology; D011355:Prodrugs / Q000494:pharmacology*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy*; D012756:Sheep
D000085:Acetates; D004731:Endotoxins; D062385:Hydroxybenzoates; D008070:Lipopolysaccharides; D011355:Prodrugs; C011748:tosiben; C044101:endotoxin, Escherichia coli