Abstract
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.
Similar content being viewed by others
Article PDF
References
Ashbaugh DG, Bigelow DB, Petty TL, Levine BE . Acute respiratory distress in adults. Lancet 1967; 2: 319–23.
Isik AF, Kati I, Bayram I, Ozbek H . A new agent for treatment of acute respiratory distress syndrome: thymoquinone. An experimental study in a rat model. Eur J Cardiothorac Surg 2005; 28: 301–5.
The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342: 1301–8.
Jain R, DalNogare A . Pharmacological therapy for acute respiratory distress syndrome. Mayo Clin Proc 2006; 81: 205–12.
Jeyaseelan S, Chu H W, Young SK, Freeman MW, Worthen GS . Distinct roles of pattern recognition receptors CD14 and Tolllike receptor 4 in acute lung injury. Infect Immun 2005; 73: 1754–63.
Piantadosi CA, Schwartz DA . The acute respiratory distress syndrome. Ann Intern Med 2004; 141: 460–70.
Lang JD, Hickman-Davis JM . One-hit, two-hit.…is there really any benefit?. Clin Exp Immunol 2005; 141: 211–4.
Ware LB, Matthay MA . The acute respiratory distress syndrome. N Engl J Med 2000; 342: 1334–49.
Welty-Wolf KE, Carraway MS, Miller DL, Ortel TL, Ezban M, Ghio AJ, et al. Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons. Am J Respir Crit Care Med 2001; 164: 1988–96.
Fan J, Kapus A, Li YH, Rizoli S, Marshall JC, Rotstein OD . Priming for enhanced alveolar fibrin deposition after hemorrhagic shock: role of tumor necrosis factor. Am J Respir Cell Mol Biol 2000; 22: 412–21.
Fan J, Kapus A, Marsden PA, Li YH, Oreopoulos G, Marshall JC, et al. Regulation of Toll-like receptor 4 expression in the lung following hemorrhagic shock and lipopolysaccharide. J Immunol 2002; 168: 5252–9.
Matthay MA, Zimmerman GA, Esmon C, Bhattacharya J, Coller B, Doerschuk CM, et al. Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group. Am J Respir Crit Care Med 2003; 167: 1027–35.
Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999; 282: 637–45.
Viereck V, Grundker C, Blaschke S, Niederkleine B, Siggelkow H, Frosch KH, et al. Raloxifene concurrently stimulates osteoprotegerin and inhibits interleukin-6 production by human trabecular osteoblasts. J Clin Endocrinol Metab 2003; 88: 4206–13.
Suuronen T, Nuutinen T, Huuskonen J, Ojala J, Thornell A, Salminen A . Anti-inflammatory effect of selective estrogen receptor modulators (SERMs) in microglial cells. Inflamm Res 2005; 54: 194–203.
Esposito E, Iacono A, Raso GM, Pacilio M, Coppola A, Di Carlo R, et al. Raloxifene, a selective estrogen receptor modulator, reduces carrageenan-induced acute inflammation in normal and ovariectomized rats. Endocrinology 2005; 146: 3301–8.
Speyer CL, Rancilio NJ, McClintock SD, Crawford JD, Gao H, Sarma JV, et al. Regulatory effects of estrogen on acute lung inflammation in mice. Am J Physiol Cell Physiol 2005; 288: C881–90.
Yu H P, Hsieh YC, Suzuki T, Shimizu T, Choudhry MA, Schwacha MG, et al. Salutary effects of estrogen receptor-β agonist on lung injury after trauma-hemorrhage. Am J Physiol Lung Cell Mol Physiol 2006; 290: L1004–9.
Lu KW, William Taeusch H, Robertson B, Goerke J, Clements JA . Polymer-surfactant treatment of meconium-induced acute lung injury. Am J Respir Crit Care Med 2000; 162: 623–8.
Wu J, Hua Y, Keep RF, Nakamura T, Hoff JT, Xi G . Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke 2003; 34: 2964–9.
Cepkova M, Matthay MA . Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome. J Intensive Care Med 2006; 21: 119–43.
Abraham E . Neutrophils and acute lung injury. Crit Care Med 2003; 4 ( Suppl 31): S195–9.
Weinacker AB, Vaszar LT . Acute respiratory distress syndrome: physiology and new management strategies. Annu Rev Med 2001; 52: 221–37.
Nemzek JA, Call DR, Ebong SJ, Newcomb DE, Bolgos GL, Remick DG . Immunopathology of a two-hit murine model of acid aspiration lung injury. Am J Physiol Lung Cell Mol Physiol 2000; 278: L512–20.
Goldman G, Welbourn R, Klausner JM, Kobzik L, Valeri CR, Shepro D, et al. Leukocytes mediate acid aspiration-induced multiorgan edema. Surgery 1993; 114: 13–20.
Chen DL, Schuster DP . Positron emission tomography with [18F]fluorodeoxyglucose to evaluate neutrophil kinetics during acute lung injury. Am J Physiol Lung Cell Mol Physiol 2004; 286: L834–40.
Love C, Tomas MB, Tronco GG, Palestro CJ . FDG PET of infection and inflammation. Radiographics 2005; 25: 1357–68.
Rini JN, Palestro CJ . Imaging of infection and inflammation with 18F-FDG-labeled leukocytes. Q J Nucl Med Mol Imaging 2006; 50: 143–6.
Vos FJ, Bleeker-Rovers CP, Corstens FH, Kullberg BJ, Oyen WJ . FDG-PET for imaging of non-osseous infection and inflammation. Q J Nucl Med Mol Imaging 2006; 50: 121–30.
Jacene HA, Cohade C, Wahl RL . F-18 FDG PET/CT in acute respiratory distress syndrome: a case report. Clin Nucl Med 2004; 29: 786–8.
Velazquez M, Weibel ER, Kuhn CD, Schuster DP . PET evaluation of pulmonary vascular permeability: a structure-function correlation. J Appl Physiol 1991; 70: 2206–16.
Schuster DP, Stark T, Stephenson J, Royal H . Detecting lung injury in patients with pulmonary edema. Intensive Care Med 2002; 28: 1246–53.
Saxton JM, Pockley AG . Effect of ex vivo storage on human peripheral blood neutrophil expression of CD11b and the stabilizing effects of Cyto-Chex. J Immunol Methods 1998; 214: 11–7.
Shang Y, Brown M . Molecular determinants for the tissue specificity of SERMs. Science 2002; 295: 2465–8.
Olivier S, Close P, Castermans E, de Leval L, Tabruyn S, Chariot A, et al. Raloxifene-induced myeloma cell apoptosis: a study of nuclear factor-kappaB inhibition and gene expression signature. Mol Pharmacol 2006; 69: 1615–23.
Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, et al. Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab 1997; 82: 4258–65.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhou, Gj., Zhang, H., Zhi, Sd. et al. Protective effect of raloxifene on lipopolysaccharide and acid- induced acute lung injury in rats. Acta Pharmacol Sin 28, 1585–1590 (2007). https://doi.org/10.1111/j.1745-7254.2007.00637.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2007.00637.x
Keywords
This article is cited by
-
Lack of SOCS3 increases LPS-induced murine acute lung injury through modulation of Ly6C(+) macrophages
Respiratory Research (2017)
-
Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair
Laboratory Investigation (2016)
-
Tanshinone IIA therapeutically reduces LPS-induced acute lung injury by inhibiting inflammation and apoptosis in mice
Acta Pharmacologica Sinica (2015)
-
Short-term glutamine supplementation decreases lung inflammation and the receptor for advanced glycation end-products expression in direct acute lung injury in mice
BMC Pulmonary Medicine (2014)