Protective effect of raloxifene on lipopolysaccharide and acid- induced acute lung injury in rats

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Aim: 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. Conclusion: Raloxifene provides a significant protective effect on acute lung injury in rats induced first by LPS ip injection and then by HCl IT instillation.

Keywords: acute lung injury; aspiration; fluorodeoxy-glucose; lipopolysaccharide; microPET; pulmonary edema; raloxifene

Document Type: Research Article


Affiliations: 1: Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University, School of Medicine and Research Institute of Emergency Medicine, Hangzhou 310009, China 2: Department of Nuclear Medicine, Second Affiliated Hospital, Zhejiang University, Hangzhou 310009, China 3: Drug Design and Discovery Center, Shanghai Institute of Materia Medica, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China

Publication date: October 1, 2007

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