Acta Scientific Medical Sciences (ISSN: 2582-0931)

Research Article Volume 4 Issue 9

Effects of a Combined Therapy of ATRA+VEGF on Distal Organs of Emphysematous Mice Model

Shivangi Mishra1, Megha Neolia1, Sherya Patil1, Amit Kumar Tyagi2 and Jai Prakash Muyal1*

1School of Biotechnology, Gautam Buddha University (GBU), Gautam Budh Nagar, Uttar Pradesh, India
2Nuclear Medicine Department, Institute of Nuclear Medicine and Allied Sciences, Defence Research Development Organization, New Delhi, India

*Corresponding Author: Jai Prakash Muyal, School of Biotechnology, Gautam Buddha University (GBU), Gautam Budh Nagar, Uttar Pradesh, India.

Received: August 05, 2020; Published: August 19, 2020



Pulmonary emphysema is principally associated with the lung. The inflammation is the main cause of emphysema that triggers release of inflammatory mediators. Such inflammatory mediators might get spilled out from the lung to the proximal and distal organs, hence may affects other organ’s functioning as well. In this light, firstly, we attempted to determine the spillage of inflammatory mediators on liver and heart organs of emphysematous lung mice model. Secondly, to elucidate the beneficial role of ATRA+VEGF supplementation towards such spillage of inflammatory mediators by studying the antioxidant levels, which leads in tissue damage and hence affects its function.

To analyse these two objectives, in silico study has been performed for the prediction of the gene interaction network between elastase, ATRA, and VEGF, respectively with extracellular regulated kinases (ERK) pathway. Furthermore, antioxidant levels and histopathology were studied in before elastase-treatment, after elastase-treatment and after elastase-treated group received ATRA+VEGF conditions using liver and heart tissues.

Elastase-treated group received ATRA+VEGF has proven to be beneficial in reducing inflammation as the levels of anti-oxidants was significantly reduced. Moreover, the tissue architecture of liver and heart was improved due to the ATRA+VEGF supplementation. At last, gene interaction network results provide a promising role of ATRA and VEGF in rectification of inflammation via involvement of spilled out inflammatory mediators. However, an elaborate experimental study is further required to investigate the beneficial role of ATRA+VEGF therapy on ERK pathway towards amelioration of inflammation.

Keywords: ATRA+VEGF Therapy; Organs; Chronic Obstructive Pulmonary Disease (COPD)



  1. S Uniyal., et al. “ATRA reduces inflammation and improves alveolar epithelium regeneration in emphysematous rat lung”. Biomedicine and Pharmacotherapy 108 (2018): 1435-1450.
  2. M King Han., et al. “Chronic Obstructive Pulmonary Disease: Definition, Clinical Manifestations, Diagnosis, and Staging”. UpToDate (2016).
  3. A Sharafkhaneh., et al. “Pathogenesis of emphysema: From the bench to the bedside”. Proceedings of the American Thoracic Society 5.4 (2008): 475-477.
  4. PJ Barnes and BR Celli. “Systemic manifestations and comorbidities of COPD”. European Respiratory Journal. 33.5 (2009): 1165-1185.
  5. AGNAA Noguera., et al. “Enhanced neutrophil response in chronic obstructive pulmonary disease”. Thorax 56 (2001): 432-437.
  6. WQ Gan., et al. “Association between chronic obstructive pulmonary disease and systemic inflammation: A systematic review and a meta-analysis”. Thorax 59.7 (2004): 574-580.
  7. P Kirkham and I Rahman. “Oxidative stress in asthma and COPD: Antioxidants as a therapeutic strategy”. Pharmacology and Therapeutics 111.2 (2006): 476-494.
  8. AMWJ Schols., et al. “Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease”. Thorax 51.8 (1996): 819-824.
  9. G De Carlo Massaro and D Massaro. “Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats”. Nature Medicine 3.6 (1997): 675-677.
  10. G NEUFELD., et al. “Vascular endothelial growth factor (VEGF) and its receptors”. FASEB Journal 13.1 (1999): 9-22.
  11. KH. “Role of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease”. Medical Science Monitor 13.11 (2007): 189-195.
  12. C Seifart., et al. “All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages”. European Respiratory Journal 38.2 (2011): 425-439.
  13. R Rodrigues., et al. “A murine model of elastase- and cigarette smoke-induced emphysema TT - Modelo murino de enfisema induzido por instilação de elastase e exposição a fumaça de cigarro”. Jornal Brasileiro de Pneumologia 43.2 (2017): 95-100.
  14. R Rodrigues., et al. “An experimental model of elastase and cigarette smoke- induced emphysema in mice”. European Respiratory Journal 44.58 (2014).
  15. AC MAEHLY and B CHANCE. “The assay of catalases and peroxidases”. Methods of Biochemical Analysis 1 (1954): 357-424.
  16. TD Mohandas J., et al. “Differential distribution of glutathione and glutathione-related enzymes in rabbit kidney. Possible implications in analgesic nephropathy”. Biochemical Pharmacology 33.11 (1984): 1801-1807.
  17. N J Sinden and R A Stockley. “Systemic inflammation and comorbidity in COPD: A result of ‘overspill’ of inflammatory mediators from the lungs? Review of the evidence”. Thorax 65.10 (2010): 930-936.
  18. R Tkacova., et al. “Metabolic phenotype and adipose tissue inflammation in patients with chronic obstructive pulmonary disease”. Mediators of Inflammation (2010).
  19. J Lee., et al. “Cigarette Smoking and Inflammation”. Journal of Dental Research 91.2 (2012): 142-149.
  20. S Uniyal., et al. “ATRA modulates gluconeogenesis and triglyceride biosynthesis pathway of liver in elastase induced emphysematous rats”. Journal of Experimental Animal Science 2.2 (2017): 109-125.
  21. W Ziaziaris and L Munoz. “Mitogen-activated protein kinase-activated protein kinase 2 in neuroinflammation, heat shock protein 27 phosphorylation, and cell cycle: Role and targeting fadi maged shokry gurgis”. Molecular Pharmacology 85.2 (2014): 345-356.
  22. H K Kim. “Role of ERK/MAPK signalling pathway in anti-inflammatory effects of Ecklonia cava in activated human mast cell line-1 cells”. Asian Pacific Journal of Tropical Medicine 7.9 (2014): 703-708.
  23. JD Becky A., et al. “Extracellular Regulated Kinase/Mitogen Activated Protein Kinase Is Up-regulated in Pulmonary Emphysema and Mediates Matrix Metalloproteinase-1 Induction by Cigarette Smoke”. Journal of Biological Chemistry 279.17 (2004): 17690-17696.
  24. J P Muyal., et al. “Effect of recombinant human keratinocyte growth factor in inducing Ras-Raf-Erk pathway-mediated cell proliferation in emphysematous mice lung”. Inhalation Toxicology 26.13 (2014): 761-771.
  25. JC., et al. “Crucial requirement of ERK/MAPK signaling in respiratory tract development”. Development 141 (2014): 3197-3211.
  26. S Singh., et al. “Evaluation of Oxidative Stress and Antioxidant Status in Chronic Obstructive Pulmonary Disease”. Scandinavian Journal of Immunology 85.2 (2017): 130-137..
  27. H Shimizu., et al. “Vascular endothelial growth factor secreted by replicating hepatocytes induces sinusoidal endothelial cell proliferation during regeneration after partial hepatectomy in rats”. Journal of Hepatology 34.5 (2001): 683-689.
  28. L Drowley., et al. “Discovery of retinoic acid receptor agonists as proliferators of cardiac progenitor cells through a phenotypic screening approach”. Stem Cells Translational Medicine 9.1 (2020): 47-60.


Citation: Jai Prakash Muyal., et al. “Effects of a Combined Therapy of ATRA+VEGF on Distal Organs of Emphysematous Mice Model". Acta Scientific Medical Sciences 4.9 (2020): 38-45.


Acceptance rate30%
Acceptance to publication20-30 days
Impact Factor1.403

Indexed In

News and Events

  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for Upcoming Issue
    The last date for submission of articles for regular Issues is July 30, 2024.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of "Best Article of the Issue"
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.

Contact US