Thalidomide reduces lipopolysaccharide/zymosan-induced acute lung injury in rats.
Pharmacological therapies targeting fulminant lung inflammation in acute lung injury (ALI) need to be improved. We evaluated the effect of thalidomide, a chemical modulating both acute and chronic inflammation, on ALI induced by intravenous administration of lipopolysaccharide (LPS) and zymosan in male Sprague-Dawley rats. Injection of LPS and zymosan induced significant lung inflammation, as evidenced by increased neutrophil sequestration in lung tissue as well as enhanced nitric oxide metabolite (NO(x)(-)) production in the serum and bronchoalveolar lavage (BAL) fluid. Lactate dehydrogenase (LDH) activity and protein concentration in BAL fluid were significantly increased after administration of LPS and zymosan. Pulmonary microvascular permeability was determined using the Evans blue retention method, which showed a significant increase in microvascular permeability after LPS and zymosan administration, indicating the development of ALI. Animals that received thalidomide (100 mg/kg) 2 h prior to LPS injection had significantly reduced pulmonary NO(x)(-) production, pulmonary microvascular permeability, and LDH activity and protein concentration in BAL fluid. We therefore conclude that thalidomide ameliorates lung inflammation and reduces ALI induced by combined LPS and zymosan administration in rats.
Graduate Institute of Medical Sciences, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan, ROC.
Chien-Sheng
CS
Chen
Wann-Cherng
WC
Perng
Chien-Wen
CW
Chen
Kun-Lun
KL
Huang
Chin-Pyng
CP
Wu
Mao-Hsiung
MH
Yen
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008070:Lipopolysaccharides / Q000633:toxicity*; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009589:Nitrogen Oxides / Q000378:metabolism; D009195:Peroxidase / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013792:Thalidomide / Q000627:therapeutic use*; D015054:Zymosan / Q000633:toxicity*
D008070:Lipopolysaccharides; D009589:Nitrogen Oxides; D013792:Thalidomide; D015054:Zymosan; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase