Protective effect of raloxifene on lipopolysaccharide and acid- induced acute lung injury in rats
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.
acute lung injury;
Document Type: Research Article
Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University, School of Medicine and Research Institute of Emergency Medicine, Hangzhou 310009, China
Department of Nuclear Medicine, Second Affiliated Hospital, Zhejiang University, Hangzhou 310009, China
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