Protective effect of raloxifene on lipopolysaccharide and acid- induced acute lung injury in rats.
OBJECTIVE
To evaluate the protective effect of oral raloxifene on acute lung injury.


METHODS
Thirty adult, male Sprague-Dawley rats each weighing 180-210 g were used and divided into 3 groups: the raloxifene-lipopolysaccharide (LPS)-HCl group (n=10), the LPS-raloxifene-HCl group (n=10), and the placebo group (n=10). All the rats were injected intraperitoneally (ip) with 5 mg/kg LPS, and raloxifene (30 mg/kg) was orally administered 1 h before and 14 h after LPS injection into the raloxifene-LPS-HCl and the LPS-raloxifene-HCl groups, respectively; the placebo group received nothing. Sixteen hours after LPS injection, all the animals were anesthetized and the femoral artery was cannulated. All the rats received a direct intratracheal (IT) injection of HCl (pH 1.2; 0.5 mL/kg). The mean arterial pressure (MAP) and blood gas concentrations were measured. Fifteen rats (5 in each group, respectively) underwent a micro positron emission tomography (microPET) scan of the thorax 4 h after HCl instillation. The wet/dry (W/D) weight ratio determination and histopathological examination were also performed.


RESULTS
The rats in the LPS-raloxifene-HCl group had a lower [18F]fluorodeoxyglucose uptake compared with the rats in the placebo group (4.67+/-1.33 vs 9.01+/-1.58, respectively, P<0.01). The rats in the LPS-raloxifene-HCl group also had a lower histological lung injury score (8.20+/-1.23 vs 12.6+/-0.97, respectively, P<0.01) and W/D weight ratio (5.335+/-0.198 vs 5.886+/-0.257, respectively, P<0.01) compared to the placebo group. The rats in this group also showed better pulmonary gas exchange and more stable mean arterial pressure (MAP) compared to the placebo group.


CONCLUSIONS
Raloxifene provides a significant protective effect on acute lung injury in rats induced first by LPS ip injection and then by HCl IT instillation.
Zhou
Guang-Ju
GJ
Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University, School of Medicine and Research Institute of Emergency Medicine, Hangzhou 310009, China.
Zhang
Hong
H
Zhi
Sheng-De
SD
Jiang
Guo-Ping
GP
Wang
Jing
J
Zhang
Mao
M
Gan
Jian-Xin
JX
Xu
Shao-Wen
SW
Jiang
Guan-Yu
GY
D000284:Administration, Oral; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D019788:Fluorodeoxyglucose F18; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D007267:Injections; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008297:Male; D049268:Positron-Emission Tomography; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology; D014132:Trachea
D008070:Lipopolysaccharides; D020011:Protective Agents; D020845:Selective Estrogen Receptor Modulators; D019788:Fluorodeoxyglucose F18; D020849:Raloxifene Hydrochloride; D006851:Hydrochloric Acid