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Amelioration of Bleomycin-Induced Acute Lung Injury and Epithelial-Mesenchymal Transition by Baicalein in Mice


Affiliations
1 Department of Veterinary Pathology, and Animal Disease Research Centre, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana 141 004, India
2 Animal Disease Research Centre, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana 141 004, India
 

During lung fibrosis, acute pulmonary inflammation and epithelial–mesenchymal transition (EMT) play important roles. The present study analyses the ameliorative effect of baicalein, a bioactive flavonoid present in the dry ischolar_mains of Scutellaria baicalensis Georgi, on bleomycin-induced acute lung injury and subsequent EMT. Mice received a single intratracheal instillation of saline containing bleomycin @1 mg/kg body wt. Baicalein in different doses (0.1, 1.0, 10 mg/kg) was given intraperitoneally daily for one week. Pulmonary inflammation and EMT parameters were evaluated. Baicalein significantly attenuated bleomycin-induced pulmonary inflammatory and structural changes. Thus, treatment with baicalein ameliorates bleomycininduced acute inflammation and subsequent early stage of EMT.

Keywords

Acute Lung Injury, Baicalein, Bleomycin, Epithelial-Mesenchymal Transition, Mice.
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  • Chen, C. M., Chou, H. C. and Huang, L. T., Maternal nicotine exposure induces epithelial–mesenchymal transition in rat offspring lungs. Neonatology, 2015, 108, 179–187.
  • Hashimoto, N., Jin, H., Liu, T., Chensue, S. W. and Phan, S. H., Bone marrow-derived progenitor cells in pulmonary fibrosis. J. Clin. Invest., 2004, 113, 243–252.
  • Willis, B. C., Liebler, J. M., Luby, P. K., Nicholson, A. G., Crandall, E. D., du Bois, R. M. and Borok, Z., Induction of epithelial– mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am. J. Pathol., 2005, 166, 1321–1332.
  • Moeller, A., Ask, K., Warburton, D., Gauldie, J. and Kolb, M., The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis? Int. J. Biochem. Cell Biol., 2008, 40(3), 362–382.
  • Borzone, G., Moreno, R., Urrea, R., Meneses, M., Oyarzún, M. and Lisboa, C., Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med., 2001, 63, 1648–1653.
  • Hashimoto, N. et al., Endothelial–mesenchymal transition in bleomycin-induced pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol., 2010, 43, 161–172.
  • Shan, H. et al., The analgesic and anti neuro inflammatory effect of baicalein in cancer-induced bone pain. J. Evid. Based Complement. Altern. Med., 2015; doi:10,1155/2015/973524.
  • Mabalirajan, U. et al., Baicalein reduces airway injury in allergen and IL-13 induced airway inflammation. PLoS ONE, 2013, 8, 62916.
  • Rafii, R., Juarez, M. M., Albertson, T. E. and Chan, A. L., A review of current and novel therapies for idiopathic pulmonary fibrosis. J. Thorac. Dis., 2013, 5, 48–73.
  • Kagalwalla, A. F. et al., Eosinophilic esophagitis: epithelialmesenchymal transition contributes to esophageal remodeling and reverses with treatment. J. Allergy Clin. Immunol., 2012, 129, 1387–1396.
  • Liu, W., Chen, X. L., Liu, J. H., Chen, C. and Ai, J., The effect of baicalein on bleomycin-induced fibrosis in lungs of rats. Chin. J. Appl. Physiol., 2009, 25, 145–149.
  • Gao, Y., Lu, J., Zhang, Y., Chen, Y., Gu, Z. and Jiang, X., Baicalein attenuates bleomycin-induced pulmonary fibrosis in rats through inhibition of miR-21. Pulm. Pharmacol. Ther., 2013, 26, 649–654.
  • Mabalirajan, U., Ahmad, T., Leishangthem, G. D., Joseph, D. A., Dinda, A. K., Agrawal, A. and Ghosh, B., Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma. J. Allergy Clin. Immunol., 2010, 125, 626–635.
  • Hübner, R. H. et al., Standardized quantification of pulmonary fibrosis in histological samples. BioTechniques, 2008, 44, 507– 517.
  • Shafiq-ur-Rehman, S., Lead-induced regional lipid peroxidation in brain. Toxicol. Lett., 1984, 21, 333–337.
  • Madesh, M. and Balasubramanian, K. A., Microtitre plate assay for superoxide dismutase using MTT reduction by superoxide. Indian J. Biochem. Biophys., 1998, 35, 184–188.
  • Singh, N. D. et al., Effect of feeding graded doses of citrinin on apoptosis and oxidative stress in male Wistar rats through the F1 generation. Toxicol. Ind. Health, 2013, 32, 385–397.
  • Lomas, N. J., Watts, K. L., Akram, K. M., Forsyth, N. R. and Spiteri, M. A., Idiopathic pulmonary fibrosis: immunohistochemical analysis provides fresh insights into lung tissue remodelling with implications for novel prognostic markers. Int. J. Clin. Exp. Pathol., 2012, 5(1), 58–71.
  • Leishangthem, G. D., Mabalirajan, U., Singh, V. P., Agrawal, A., Ghosh, B. and Dinda, A. K., Ultrastructural changes of airway in murine models of allergy and diet-induced metabolic syndrome. ISRN Allergy, 2013; doi:10,1155/2013/261297.
  • Serhan, C. N. et al., Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous anti-inflammatory lipid mediators. J. Immunol., 2003, 171, 6856–6865.
  • Goto, H., Ledford, J. G., Mukherjee, S., Noble, P. W., Williams, K. L. and Wright, J. R., The role of surfactant protein A in bleomycin induced acute lung injury. Am. J. Respir. Crit. Care Med., 2010, 181, 1336–1344.
  • Mutsaers, S. E., Foster, M. L., Chambers, R. C., Laurent, G. J. and McAnulty R. J., Increased endothelin-1 and its localization during the development of bleomycin-induced pulmonary fibrosis in rats. Am. J. Respir. Cell. Mol. Biol., 1998, 18, 611–619.
  • Dinda, B., Dinda, S., DasSharma, S., Banik, R., Chakraborty, A. and Dinda, M., Therapeutic potentials of baicalin and it’s aglycone, baicalein against inflammatory disorders. Eur. J. Med. Chem., 2017, 131, 68–80.
  • Tanjore, H. et al., Contribution of epithelial-derived fibroblasts to bleomycin-induced lung fibrosis, Am. J. Respir. Crit. Care Med., 2009, 180, 657–665.
  • Li, L. F. et al., Mechanical ventilation augments bleomycininduced epithelial–mesenchymal transition through the Src pathway. Lab. Invest., 2014, 94(9), 1017–1029.
  • Geng, X., Dufu, K. and Hutchaleelaha, A., Increased hemoglobin–oxygen affinity ameliorates bleomycin‐induced hypoxemia and pulmonary fibrosis. Physiol. Rep., 2006; doi:10,14814/phy2,12965.
  • Ware, L. B. and Matthay, M. A., Clinical practice, acute pulmonary edema. N. Engl. J. Med., 2005, 353, 2788–2796.
  • Tsai, C. L., Lin, Y. C., Wang, H. M. and Chou, T. C., Baicalein, an active component of Scutellaria baicalensis, protects against lipopolysaccharide-induced acute lung injury in rats. J. Ethnopharmacol., 2014, 153, 197–206.
  • Reutershan, J., Basit, A., Galkina, E. V. and Ley, K., Sequential recruitment of neutrophils into lung and bronchoalveolar lavage fluid in LPS-induced acute lung injury. Am. J. Physiol. – Lung Cell. Mol. Physiol., 2005, 289, 807–815.
  • Grommes, J. and Soehnlein, O., Contribution of neutrophils to acute lung injury. Mol. Med., 2011, 17, 293–307.
  • Agouridakis, P., Kyriakou, D., Alexandrakis, M. G., Prekates, A., Perisinakis, K., Karkavitsa, N. and Bouros, D., The predictive role of serum and bronchoalveolar lavage cytokines and adhesion molecules for acute respiratory distress syndrome development and outcome. Respir. Res., 2002, 3, 25.
  • Bhatia, M. and Moochhala, S. J., Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J. Pathol., 2004, 202, 145–156.
  • Martin, W. J. and Kachel, D. L., Bleomycin-induced pulmonary endothelial cell injury: evidence for the role of iron-catalyzed toxic oxygen-derived species. J. Lab. Clin. Med., 1987, 110, 153–158.
  • Yoshino, M. and Murakami, K., Interaction of iron with polyphenolic compounds: application to antioxidant characterization. Anal. Biochem., 1998, 257, 40–44.

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  • Amelioration of Bleomycin-Induced Acute Lung Injury and Epithelial-Mesenchymal Transition by Baicalein in Mice

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Authors

Dheeraj Kumar Sharma
Department of Veterinary Pathology, and Animal Disease Research Centre, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana 141 004, India
Nittin Dev Singh
Department of Veterinary Pathology, and Animal Disease Research Centre, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana 141 004, India
Geeta Devi Leishangthem
Animal Disease Research Centre, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana 141 004, India
Harmanjit Singh Banga
Department of Veterinary Pathology, and Animal Disease Research Centre, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana 141 004, India

Abstract


During lung fibrosis, acute pulmonary inflammation and epithelial–mesenchymal transition (EMT) play important roles. The present study analyses the ameliorative effect of baicalein, a bioactive flavonoid present in the dry ischolar_mains of Scutellaria baicalensis Georgi, on bleomycin-induced acute lung injury and subsequent EMT. Mice received a single intratracheal instillation of saline containing bleomycin @1 mg/kg body wt. Baicalein in different doses (0.1, 1.0, 10 mg/kg) was given intraperitoneally daily for one week. Pulmonary inflammation and EMT parameters were evaluated. Baicalein significantly attenuated bleomycin-induced pulmonary inflammatory and structural changes. Thus, treatment with baicalein ameliorates bleomycininduced acute inflammation and subsequent early stage of EMT.

Keywords


Acute Lung Injury, Baicalein, Bleomycin, Epithelial-Mesenchymal Transition, Mice.

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DOI: https://doi.org/10.18520/cs%2Fv119%2Fi6%2F962-972