Erythropoietin attenuates lung injury in lipopolysaccharide treated rats.
BACKGROUND
Erythropoietin (EPO) elicits protective effects in lung ischemia-reperfusion, hyperoxia, acute necrotizing pancreatitis, and some other tissues. In the present study, we investigated the possible protective roles of EPO in the lipopolysaccharide (LPS) induced lung injury.


METHODS
Male Sprague-Dawley rats were treated with EPO (3000 U/kg, i.p.) or vehicle (saline), 30 min prior to LPS administration (6 mg/kg, i.v.). Four h following LPS injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Validated methods were used to measure wet/dry ratios (W/D), myeloperoxidase (MPO) activity, malondialdehyde (MDA) concentrations, and nitrite/nitrate (NO(2)(-)/NO(3)(-)) levels in lungs. Western blotting was performed to study the pulmonary expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine protein.


RESULTS
Pretreatment with EPO led to (1) significant attenuation of endotoxemia induced evident lung histologic injury and edema; (2) inhibition of LPS mediated induction in MPO activity and MDA concentration; (3) inhibition of LPS mediated overproduction of pulmonary NO(2)(-)/NO(3)(-) levels; and (4) marked suppression in endotoxin induced expression of iNOS and nitrotyrosine.


CONCLUSIONS
This study provides considerable evidence that EPO has an ability to significantly attenuate endotoxin-induced acute lung injury in rats.
Shang
You
Y
Department of Anesthesiology and Intensive Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. shang_you@126.com
Li
Xingwang
X
Prasad
Pramod V
PV
Xu
Sanpeng
S
Yao
Shanglong
S
Liu
Dong
D
Yuan
Shiying
S
Feng
Dan
D
D000818:Animals; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D004921:Erythropoietin; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat