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Intranasal Curcumin Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice

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Abstract

Lipopolysaccharide (LPS) is one of the most powerful proinflammatory factor and can induce acute pulmonary inflammation even lung injury after inhalation or systemic administration. LPS induces sepsis and multiple organ damage. Curcumin (diferuloylmethane), a major component of turmeric, exhibits protection against LPS-induced acute lung injury (ALI). We aimed to investigate effects of intranasal curcumin on LPS-induced ALI in mice where curcumin (10 mg/kg, intranasal (i.n.) was given an hour before LPS exposure. After 24 h of intranasal LPS instillation, a marked increase in neutrophil recruitment and myeloperoxidase (MPO) activity was noted which were significantly ameliorated in curcumin treatment group. Oxidative stress markers like nitric oxide (NO), malondialdehyde (MDA) level and evans blue capillary leakage assay also revealed suppression after curcumin treatment; interestingly, levels of anti-oxidative enzymes such as superoxide dismutase (SOD) and catalase were upregulated. Inflammatory cytokine, tumour necrosis factor alpha (TNF-α) level was significantly attenuated by curcumin. Hence, intranasal curcumin could be a novel therapeutic strategy for LPS-induced ALI by directly targeting the lungs and enhancing anti-oxidant levels.

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References

  1. Ware, L.B., and M.A. Matthay. 2000. The acute respiratory distress syndrome. New England Journal of Medicine 342: 1334–1349.

    Article  PubMed  CAS  Google Scholar 

  2. Dossow-Hanfstingl, V.V. 2012. Advances in therapy for acute lung injury. Anesthesiology Clinics 30: 629–639.

    Article  Google Scholar 

  3. Matthay, M.A., L.B. Ware, and G.A. Zimmerman. 2012. The acute respiratory distress syndrome. Journal of Clinical Investigation 122: 2731–2740.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Dowdy, D.W., M.P. Eid, C.R. Dennison, P.A. Mendez-Tellez, M.S. Herridge, E. Guallar, and D.M. Needham. 2006. Quality of life after acute respiratory distress syndrome: A meta-analysis. Intensive Care Medicine 3: 1115–1124.

    Article  Google Scholar 

  5. Montgomery, A.B..., M.A. Stager, C.J. Carrico, and L.D. Hudson. 1985. Causes of mortality in patients with the adult respiratory distress syndrome. American Review Respiratory Disease 132: 485–489.

    CAS  Google Scholar 

  6. Armstrong, L.A.R., K.M. Medford, J. Uppington, I. Robertson, R. Witherden, R. Witherden, T.D. Tetley, and A.B... Millar. 2004. Expression of functional toll-like receptor-2 and-4 on alveolar epithelial cells. American Journal of Respiratory Cell Molecular Biology 31: 241–245.

  7. Hallstrand, T.S., T.L. Hackett, W.A. Altemeier, G. Matute-Bello, P.M. Hansbro, and D.A. Knight. 2014. Airway epithelial regulation of pulmonary immune homeostasis and inflammation. Clinical Immunology 151: 1–15.

    Article  PubMed  CAS  Google Scholar 

  8. Goodman, R.B., J. Pugin, J.S. Lee, and M.A. Matthay. 2003. Cytokine-mediated inflammation in acute lung injury. Cytology and growth factor review 14: 523–535.

    Article  CAS  Google Scholar 

  9. Reutershan, J., A. Basit, E.V. Galkina, and K. Ley. 2005. Sequential recruitment of neutrophils into lung and bronchoalveolar lavage fluid in LPS-induced acute lung injury. American Journal of Physiology Lung Cell Molecular Physiology 289: 807–815.

    Article  CAS  Google Scholar 

  10. Abraham, E. 2003. Neutrophils and acute lung injury. Critical Care Med 31: 195–199.

    Article  Google Scholar 

  11. Chow, C.W., A.M.T. Herrera, T. Suzuki, and G.P. Downey. 2003. Oxidative stress and acute lung injury. American Journal of Respiratory Cell Molecular Biology 29: 427–431.

    Article  PubMed  CAS  Google Scholar 

  12. Chabot, F., J.A. Mitchell, J.M. Gutteridge, and T.W. Evans. 1998. Reactive oxygen species in acute lung injury. European Respiratory Journal 11: 745–757.

    PubMed  CAS  Google Scholar 

  13. Boueiz, A., and P.M. Hassoun. 2009. Regulation of endothelial barrier function by reactive oxygen and nitrogen species. Microvascular Research 77: 26–34.

    Article  PubMed  CAS  Google Scholar 

  14. Fialkow, L., F.L. Fochesatto, M.C. Bozzetti, A.R. Milani, F. Rodrigues, E.M. Ladniuk, et al. 2006. Neutrophil apoptosis: A marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome. Critical Care 10: 155.

    Article  Google Scholar 

  15. Kebir, E.D., and J.G. Filep. 2013. Targeting neutrophil apoptosis for enhancing the resolution of inflammation. Cell 2: 330–348.

    Article  CAS  Google Scholar 

  16. Gupta, S.C., S. Patchva, W. Koh, and B.B. Aggarwal. 2012. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clinical and Experimental Pharmacology and Physiology 39: 283–299.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Jobin, C., C.A. Bradham, M.P. Russo, B. Juma, A.S. Narula, D.A. Brenner, et al. 1999. Curcumin blocks cytokine-mediated NF-κB activation and proinflammatory gene expression by inhibiting inhibitory factor I-κB kinase activity. Journal of Immunology 163: 3474–3483.

    CAS  Google Scholar 

  18. Abe, Y., S.H.U. Hashimoto, and T. Horie. 1999. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacological Research 39: 41–47.

    Article  PubMed  CAS  Google Scholar 

  19. Xiao, X., M. Yang, D. Sun, and S. Sun. 2012. Curcumin protects against sepsis-induced acute lung injury in rats. Journal of Surgical Research 176: 31–39.

    Article  CAS  Google Scholar 

  20. Gunaydın, M., A. Guzel, A. Guze, H. Alacam, O. Salis, N. Murat, and T. Guvenc. 2012. The effect of curcumin on lung injuries in a rat model induced by aspirating gastrointestinal decontamination agents. Journal of Pediatric Surgery 47: 1669–1676.

    Article  PubMed  Google Scholar 

  21. Xu, F., S.H. Lin, Y.Z. Yang, R. Guo, J. Cao, and Q. Liu. 2013. The effect of curcumin on sepsis-induced acute lung injury in a rat model through the inhibition of the TGF-β1/SMAD3 pathway. International Immunopharmacology 16: 1–6.

    Article  PubMed  CAS  Google Scholar 

  22. Smith, M.R., S.R. Gangireddy, V.R. Narala, C.M. Hogaboam, T.J. Standiford, P.J. Christensen, and R.C. Reddy. 2010. Curcumin inhibits fibrosis-related effects in IPF fibroblasts and in mice following bleomycin-induced lung injury. American Journal of Physiol-Lung Cell and Molecular Physiology 298: 616–625.

    Article  CAS  Google Scholar 

  23. Bansal, S., and S. Chhibber. 2010. Curcumin alone and in combination with augmentin protects against pulmonary inflammation and acute lung injury generated during Klebsiella pneumonia B5055-induced lung infection in BALB/c mice. Journal of Medical Microbiology 59: 429–437.

    Article  PubMed  CAS  Google Scholar 

  24. Zhu, R.F., M. Zhou, J.L. He, F.Y. Ding, S.Q. Yu, and G.L. Xu. 2008. Protective effect of curcumin on oleic-induced acute lung injury in rats. Zhongguo Zhong Yao Za Zhi 33: 2141–2145.

    PubMed  CAS  Google Scholar 

  25. Lian, Q., X. Li, Y. Shang, S. Yao, L. Ma, and S. Jin. 2006. Protective effect of curcumin on endotoxin-induced acute lung injury in rats. Journal of Huazhong University of Science and Technology 26: 678–681.

    Article  PubMed  CAS  Google Scholar 

  26. Subhashini, P.S. Chauhan, S. Kumari, P. Jarajana, R. Chawla, D. Dash, et al. 2013. Intranasal curcumin and its evaluation in murine model of asthma. International Immunopharmacology 17: 733–743.

    Article  PubMed  CAS  Google Scholar 

  27. Chauhan, P.S., Subhashini, Dash D., and Singh R. 2014. Intranasal curcumin attenuates airway remodeling in murine model of chronic asthma. International Immunopharmacology 21: 63–75.

  28. Aggarwal, B.B., A. Kumar, and A.C. Bharti. 2003. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Research 23: 363–398.

    PubMed  CAS  Google Scholar 

  29. Pan, M.H., T.M. Huang, and J.K. Lin. 1999. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metabolism and Disposition 27: 486–494.

    PubMed  CAS  Google Scholar 

  30. Martin, Y., C. Avendano, M.J. Piedras, and A. Krzyzanowska. 2010. Evaluation of Evans Blue extravasations as a measure of peripheral inflammation. Protocol Exchange. doi:10.1038/2010.209.

    Google Scholar 

  31. Yin, H., X.B. Jin, Q. Gong, H. Yang, L.Y. Hu, F.L. Gong, et al. 2008. Fructose-1,6-diphosphate attenuates acute lung injury induced by lipopolysaccharide in mice. International Immunopharmacology 8: 1842–1847.

    Article  PubMed  CAS  Google Scholar 

  32. Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the folin phenol reagent. Journal of Biological Chemistry 193: 265–275.

    PubMed  CAS  Google Scholar 

  33. Bradley, P.P., R.D. Christensen, and G. Rothstein. 1982. Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood 60: 618–622.

    PubMed  CAS  Google Scholar 

  34. Guzel, N.A., S. Hazar, and D. Erbas. 2007. Effects of different resistance exercise protocols on nitric oxide, lipid peroxidation and creatine kinase activity in sedentary males. Journal of Sports Science and Medicine 6: 417.

    PubMed Central  PubMed  Google Scholar 

  35. Das, K., L. Samanta, and G.B.N. Chainy. 2000. A modified spectrophotometric assay of superoxide dismutase using nitrite formation by superoxide radicals. Indian Journal of Biochemistry Biophysics 37: 201–204.

    CAS  Google Scholar 

  36. Aebi, H. 1974. Methods of enzymatic analysis. American Journal of Pathology 176: 764–773.

    Google Scholar 

  37. Ohkawa, H., N. Ohishi, and K. Yagi. 1979. Assay for lipid peroxides in animal tissues thiobarbituric acid reaction. Analytical Biochemistry 95: 351–358.

    Article  PubMed  CAS  Google Scholar 

  38. Madan, B., and B. Ghosh. 2003. Diferuloylmethane inhibits neutrophil infiltration and improves survival of mice in high-dose endotoxin shock. Shock 19: 91–96.

    Article  PubMed  CAS  Google Scholar 

  39. Pittet, J.F., R.C. Mackersie, T.R. Martin, and M.A. Matthay. 1997. Biological markers of acute lung injury: Prognostic and pathogenetic significance. American Journal of Respiratory and Critical Care Medicine 15: 1187–1205.

    Article  Google Scholar 

  40. Grommes, J., and O. Soehnlein. 2011. Contribution of neutrophils to acute lung injury. Molecular Medicine 17: 293.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  41. Kaur, G., N. Tirkey, S. Bharrhan, V. Chanana, P. Rishi, and K. Chopra. 2006. Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin‐induced experimental hepatoxicity in rodents. Clinical and Experimental Immunology 145: 313–321.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  42. Eybl, V., D. Kotyzova, and M. Bludovska. 2004. The effect of curcumin on cadmium-induced oxidative damage and trace elements level in the liver of rats and mice. Toxicology Letters 151: 79–85.

    Article  PubMed  CAS  Google Scholar 

  43. Bhatia, M., and S. Moochhala. 2004. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. Journal of Pathology 202: 145–156.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by a grant from the Department of Science and Technology, Science and Engineering Research Board, (DST-SERB), New Delhi, India.

Conflict of Interest

Authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Zoology, MMV, Banaras Hindu University, Varanasi, 221005, India

    Asha Kumari, Namitosh Tyagi & Rashmi Singh

  2. Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India

    D Dash

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  1. Asha Kumari
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  2. Namitosh Tyagi
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  4. Rashmi Singh
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Correspondence to Rashmi Singh.

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Kumari, A., Tyagi, N., Dash, D. et al. Intranasal Curcumin Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice. Inflammation 38, 1103–1112 (2015). https://doi.org/10.1007/s10753-014-0076-y

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