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

Abstract

To evaluate the protective effect of oral raloxifene on acute lung injury. 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. 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. Raloxifene provides a significant protective effect on acute lung injury in rats induced first by LPS ip injection and then by HCl IT instillation.