Pulmonary fibrosing diseases: A short review and a therapeutic alternative

Luana Oliveira Prata; Celso Martins Queiroz-Junior; Carolina Rego Rodrigues; Fabrício Marcus Silva Oliveira; Anderson José Ferreira; Maria da Glória Rodrigues-Machado; Marcelo Vidigal Caliari

doi:10.30574/gscbps.2021.14.1.0417

Authors

Luana Oliveira Prata Postgraduate Program in Pathology, Institute of Biological Sciences, Federal University of Minas Gerais. Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, Brazil.
Celso Martins Queiroz-Junior Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais. Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, Brazil.
Carolina Rego Rodrigues Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais. Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, Brazil.
Fabrício Marcus Silva Oliveira Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais. Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, Brazil.
Anderson José Ferreira Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais. Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, Brazil.
Maria da Glória Rodrigues-Machado Medical Sciences Faculty of Minas Gerais, Alameda Ezequiel Dias 275, Belo Horizonte, Minas Gerais, Brazil.
Marcelo Vidigal Caliari Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais. Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, Brazil.

DOI:

https://doi.org/10.30574/gscbps.2021.14.1.0417

Keywords:

Pulmonary Fibrosis, Physical Training, Angiotensin Converting Enzyme 2 (ACE 2), Diminazene Aceturate (DIZE).

Abstract

Pulmonary interstitial diseases are characterized by a wide spectrum of alterations, with idiopathic pulmonary fibrosis (IPF) being one of the most important. Recent studies have shown that COVID-19 can also progress to pulmonary fibrosis. IPF affects elderly individuals, its etiological agent is unknown and its prognosis is poor. Studies have shown an increased incidence and prevalence of IPF, especially in males. Unordered and excessive extracellular matrix deposition is the main lesion of IPF, leading to loss of normal alveolar architecture, decreased pulmonary compliance, and reduced gas exchange. Clinical trials of conventional treatments have not shown significant improvement in patients with IPF, proving the need of more effective alternatives.

Studies have shown the association of angiotensin-converting enzyme (ACE)/Angiotensin (Ang)II/AT1 receptor axis with the development of pulmonary fibrosis and hypertension. On the other hand, it was observed that angiotensin 2 converting enzyme (ACE 2)/Angiotensin1-7[Ang-(1-7)]/Mas receptor axis plays an important role in the balance of the ACE/AngII/AT1 axis. In this sense, drugs that increase the activity of the ACE 2/Ang-(1-7)/Mas receptor axis could present therapeutic potential for the treatment of IPF. In addition, when the effects of ACE 2 pharmacological treatment associated with a swimming protocol were analyzed in an experimental model of bleomycin-induced lung lesions, a potent reduction of pulmonary fibrosis and an increase in endurance capacity of animals were observed. Even without fully understanding the mechanisms involved, the results of this study showed that the combination of these two treatment methods might contribute to the treatment of fibrosing interstitial lung diseases.

Metrics

Metrics Loading ...

References

Meyer KC. Diagnosis and management of interstitial lung disease. Transl Respir Med 2014; 2: 1-13.

Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet 2017; 389: 1941–52.

Dai H, Zhang X, Xia J, Zhang T, Shang Y, Huang R, et al. High-resolution Chest CT Features and Clinical Characteristics of Patients Infected with COVID-19 in Jiangsu, China. Int J Infect Dis. 2019; 51: 186–02.

WHO. (World Health Organization): Coronavirus disease (COVID-2019) situation report. 2020; 51.

WHO. World Health Organization. Coronavirus disease (COVID-2019). Situation Report 99.

Thompson BT, Chambers RC, Liu KD. Acute Respiratory Distress Syndrome. N Engl J Med 2017; 377: 562–72.

Ratjen F, Bell SC, Rowe SM, Goss CH, Quittner AL, Bush A. Cystic fibrosis. Nat Rev Dis Prim. 2015; 1: 1-19.

Wolters PJ, Collard HR, Jones KD. Pathogenesis of Idiopathic Pulmonary Fibrosis. Annu Rev Pathol Mech Dis. 2014; 9: 157–79.

Olson AL, Gifford AH, Inase N, Fernández Pérez ER, Suda T. The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype. Eur Respir Rev 2018; 27(150), 180077.

Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011; 183: 788–24.

Hutchinson J, Fogarty A, Hubbard R, McKeever T. Global incidence and mortality of idiopathic pulmonary fibrosis: A systematic review. Eur Respir J. 2015; 46: 795–06.

Natsuizaka M, Chiba H, Kuronuma K, Otsuka M, Kudo K, Mori M, et al. Epidemiologic survey of Japanese patients with idiopathic pulmonary fibrosis and investigation of ethnic differences. Am J Respir Crit Care Med. 2014; 190: 773–9.

Baddini-Martinez J, Pereira CA. Quantos pacientes com fibrose pulmonar idiopática existem no Brasil? J Bras Pneumol. 2015; 41: 560–1.

Algranti E, Saito CA, Silva DRM e, Carneiro APS, Bussacos MA. Mortality from idiopathic pulmonary fibrosis: a temporal trend analysis in Brazil, 1979-2014. J Bras Pneumol. 2017; 43: 445–50.

Zoz DF, Lawson WE, Blackwell TS. Idiopathic pulmonary fibrosis: A disorder of epithelial cell dysfunction. Am J Med Sci. 2011; 341: 435–8.

Sugahara K, Tokumine J, Teruya K, Oshiro T. Alveolar epithelial cells: Differentiation and lung injury. Respirology. 2006; 11: 28–31.

McElroy MC, Kasper M. The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair. Eur Respir J. 2004; 24: 664–73.

Han SH, Mallampalli RK. The role of surfactant in lung disease and host defense against pulmonary infections. Ann Am Thorac Soc. 2015; 12: 765–74.

Greene KE, King JE, Kuroki Y, Bucher-Bartelson B, Hunninghake GW, Newman LS, et al. Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis. Eur Respir J 2002;19:439–46.

Chapman HA. Disorders of lung matrix remodelling. J Clin Invest. 2004; 113: 148–57.

Gharaee-Kermani M, Gyetko MR, Hu B, Phan SH. New insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis: A potential role for stem cells in the lung parenchyma and implications for therapy. Pharm Res. 2007; 24: 819–41.

Willis BC, Liebler JM, Luby-Phelps K, Nicholson AG, Crandall ED, Du Bois RM, et al. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-β1: Potential role in idiopathic pulmonary fibrosis. Am J Pathol. 2005; 166: 1321–32.

Phan SH. Biology of Fibroblasts and Myofibroblasts. Proc Am Thorac Soc. 2008; 5: 334–7.

Plantier L, Cazes A, Dinh-Xuan AT, Bancal C, Marchand-Adam S, Crestani B. Physiology of the lung in idiopathic pulmonary fibrosis. Eur Respir Rev. 2018; 27: 1–14.

Laurent GJ, McAnulty RJ, Hill M, Chambers R. Escape from the matrix: Multiple mechanisms for fibroblast activation in pulmonary fibrosis. Proc Am Thorac Soc. 2008; 5: 311–5.

Burgstaller G, Oehrle B, Gerckens M, White ES, Schiller HB, Eickelberg O. The instructive extracellular matrix of the lung: basic composition and alterations in chronic lung disease. Eur Respir J. 2017; 50: 1601805.

Glasser SW, Hagood JS, Wong S, Taype CA, Madala SK, Hardie WD. Mechanisms of Lung Fibrosis Resolution. Am J Pathol. 2016; 186: 1066–77.

Corbel M, Boichot E, Lagente V. Role of gelatinases MMP-2 and MMP-9 in tissue remodeling following acute lung injury. Brazilian J Med Biol Res. 2000; 33: 749–54.

Pardo A, Selman M. Matrix metalloproteases in aberrant fibrotic tissue remodeling. Proc Am Thorac Soc. 2006; 3: 383–8.

Greenlee KJ, Werb Z, Kheradmand F. Matrix metalloproteinases in lung: Multiple, multifarious, and multifaceted. Physiol Rev. 2007; 87: 69–98.

Kim JY, Choeng HC, Ahn C, Cho SH. Early and late changes of MMP-2 and MMP-9 in bleomycin-induced pulmonary fibrosis. Yonsei Med J. 2009; 50: 68–77.

Mura M, Ferretti A, Ferro O, Zompatori M, Cavalli A, Schiavina M, et al. Functional predictors of exertional dyspnea, 6-min walking distance and HRCT fibrosis score in idiopathic pulmonary fibrosis. Respiration. 2006; 73: 495–02.

Richeldi L, Du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014; 370: 2071–82.

Noble PW, Albera C, Bradford WZ, Costabel U, Bois RMD, Fagan EA, et al. Pirfenidone for idiopathic pulmonary fibrosis: Analysis of pooled data from three multinational phase 3 trials. Eur Respir J. 2016; 47: 243–53.

Kim ES, Keating GM. Pirfenidone: A review of its use in idiopathic pulmonary fibrosis. Drugs. 2015; 75: 219–30.

Ahluwalia N, Shea BS, Tager AM. New Therapeutic Targets in Idiopathic Pulmonary Fibrosis. Aiming to Rein in Runaway Wound-Healing Responses. Am J Respir Crit Care Med. 2014; 190: 867–78.

Wollin L, Maillet I, Quesniaux V, Holweg A, Ryffel B. Antifibrotic and anti-inflammatory activity of the Tyrosine Kinase inhibitor Nintedanib in Experimental Models Of Lung Fibrosiss. J Pharmacol Exp Ther. 2014; 349: 209–20.

Wollin L, Wex E, Pautsch A, Schnapp G, Hostettler KE, Stowasser S, et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J. 2015; 45: 1434–45.

Hilberg F, Tontsch-Grunt U, Baum A, Le AT, Doebele RC, Lieb S, et al. Triple angiokinase inhibitor nintedanib directly inhibits tumor cell growth and induces tumor shrinkage via blocking oncogenic receptor tyrosine kinases. J Pharmacol Exp Ther. 2018; 364: 494–03.

Graney BA, Lee JS. Impact of novel antifibrotic therapy on patient outcomes in idiopathic pulmonary fibrosis: patient selection and perspectives. Patient Relat Outcome Meas. 2018;9: 321–8.

Prata LO, Oliveira FMS, Ribeiro TMS, Almeida PWM, Cardoso JA, Rodrigues-Machado M da G, et al. Exercise attenuates pulmonary injury in mice with bleomycin-induced pulmonary fibrosis. Exp Biol Med. 2012; 237: 873–83.

Watson RA, De La Peña H, Tsakok MT, Joseph J, Stoneham S, Shamash J, et al. Development of a best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours in the UK. Br J Cancer. 2018; 119: 1044–51.

Moore BB, Hogaboam CM. Murine models of pulmonary fibrosis. Am J Physiol - Lung Cell Mol Physiol. 2008; 294: 152–60.

Hay J, Shahzeidi S, Laurent G. Mechanisms of bleomycin-induced lung damage. Arch Toxicol. 1991; 65: 81–94..

Martin WG, Ristow KM, Habermann TM, Colgan JP, Witzig TE, Ansell SM. Bleomycin pulmonary toxicity has a negative impact on the outcome of patients with Hodgkin’s lymphoma. J Clin Oncol. 2005; 23: 7614–20.

Azambuja E, Fleck JF, Batista RG, Menna Barreto SS. Bleomycin lung toxicity: who are the patients with increased risk? Pulm Pharmacol Ther. 2005; 18: 363–6.

Ferreira AJ, Shenoy V, Yamazato Y, Sriramula S, Francis J, Yuan L, et al. Evidence for angiotensin-converting enzyme 2 as a therapeutic target for the prevention of pulmonary hypertension. Am J Respir Crit Care Med. 2009; 179: 1048–54.

Ferreira AJ, Santos RA, Almeida AP. Angiotensin-(1-7): cardioprotective effect in myocardial ischemia/reperfusion. Hypertension. 2001; 38: 665–8.

Tallant EA, Ferrario CM, Gallagher PE. Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor. Am J Physiol - Hear Circ Physiol. 2005; 289: 1560–6.

Ferrario CM. Angiotensin-converting enzyme 2 and angiotensin-(1-7): An evolving story in cardiovascular regulation. Hypertension. 2006; 47: 515–21.

Oudit GY, Kassiri Z, Patel MP, Chappell M, Butany J, Backx PH, et al. Angiotensin II-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice. Cardiovasc Res. 2007; 75: 29–39.

Fraga-Silva RA, Pinheiro SVB, Gonçalves ACC, Alenina N, Bader M, Souza Dos Santos RA. The antithrombotic effect of angiotensin-(1-7) involves Mas-mediated NO release from platelets. Mol Med. 2008; 14: 28–35.

Mercure C, Yogi A, Callera GE, Aranha AB, Bader M, Ferreira AJ, et al. Angiotensin(1-7) blunts hypertensive cardiac remodeling by a direct effect on the heart. Circ Res. 2008; 103: 1319–26.

Shenoy V, Ferreira AJ, Qi Y, Fraga-Silva RA, Díez-Freire C, Dooies A, et al. The angiotensin-converting enzyme 2/angiogenesis-(1-7)/Mas axis confers cardiopulmonary protection against lung fibrosis and pulmonary hypertension. Am J Respir Crit Care Med. 2010; 182: 1065–72.

Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme: Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000; 275: 33238–43.

Santos RAS, Simoes e Silva AC, Maric C, Silva DMR, Machado RP, De Buhr I, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003; 100: 8258–63.

Rigatto K, Casali KR, Shenoy V, Katovich MJ, Raizada MK. Diminazene aceturate improves autonomic modulation in pulmonary hypertension. Eur J Pharmacol. 2013; 713: 89–93.

Kuriakose S, Uzonna JE. Diminazene aceturate (Berenil), a new use for an old compound? Int Immunopharmacol. 2014; 21: 342–5.

Richard Brodersen HL, Kelkheim e Heinrich Ott. Readily’soluble and stable salts of DI. (4-AMIDINO-PHENYL) - TRIAZENE - (N-13) and a process of preparing them. United States Pat Off. Patented: June 10, 1958.

Heinrich Jensch Hochst FHA. BAsic diazoamanobenzene compounds. United States Pat Off. Patented. 23 Mar 1954.

Vial HJ, Gorenflot A. Chemotherapy against babesiosis. Vet Parasitol. 2006; 138: 147–60.

Gohil S, Herrmann S, Günther S, Cooke BM. Bovine babesiosis in the 21st century: Advances in biology and functional genomics. Int J Parasitol. 2013; 43: 125–32.

Mamman M, Aliu YO, Peregrine AS. Comparative pharmacokinetics of diminazene in noninfected Boran (Bos indicus) cattle and Boran cattle infected with Trypanosoma congolense. Antimicrob Agents Chemother. 1993; 37: 1050–5.

Onyeyili PA, Anika SM. The influence of Trypanosoma congolense infection on the disposition kinetics of diminazene aceturate in the dog. Vet Res Commun. 1989; 13: 231–6.

González VM, Pérez JM, Alonso C. The berenil ligand directs the DNA binding of the cytotoxic drug Pt- berenil. J Inorg Biochem. 1997; 68: 283–7.

T Haaf’, W Feichtinger, M Guttenbach, L Sanchez, CR Müller, MS. Berenil-induced undercondensation in human heterochromatin. Cytogenet Cell Genet. 1989; 50: 27-33.

Poot M, Kausch K, Köhler J, Haaf T, Hoehn H. The Minor-Groove Binding DNA-Ligands Netropsin, Distamycin A and Berenil Cause Polyploidisation via Impairment of the G2 Phase of the Cell Cycle. Cell Struct Funct. 1990; 15: 151–7.

Uzonna JE, Kaushik RS, Gordon JR, Tabel H. Cytokines and antibody responses during Trypanosoma congolense infections in two inbred mouse strains that differ in resistance. Parasite Immunol. 1999; 21: 57–71.

Kuriakose S, Muleme HM, Onyilagha C, Singh R, Jia P, Uzonna JE. Diminazene Aceturate (Berenil) Modulates the Host Cellular and Inflammatory Responses to Trypanosoma congolense Infection. PLoS One. 2012; 7: 1–8.

Kulemina L V., Ostrov DA. Prediction of off-target effects on angiotensin-converting enzyme 2. J Biomol Screen. 2011; 16: 878–85.

Shenoy V, Gjymishka A, Jarajapu YP, Qi Y, Afzal A, Rigatto K, et al. Diminazene attenuates pulmonary hypertension and improves angiogenic progenitor cell functions in experimental models. Am J Respir Crit Care Med. 2013; 187: 648–57.

Mecca AP, Regenhardt RW, O’Connor TE, Joseph JP, Raizada MK, Katovich MJ, et al. Cerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke. Exp Physiol. 2011; 96: 1084–96.

Foureaux G, Nogueira JC, Nogueira BS, Fulgêncio GO, Menezes GB, Fernandes SOA, et al. Antiglaucomatous effects of the activation of intrinsic angiotensin-converting enzyme 2. Investig Ophthalmol Vis Sci. 2013; 54: 4296–306.

Vainshelboim B. Exercise training in idiopathic pulmonary fibrosis: Is it of benefit? Breathe. 2016; 12: 130–8.

Spruit MA, Janssen DJA, Franssen FME, Wouters EFM. Rehabilitation and palliative care in lung fibrosis. Respirology. 2009; 14: 781–7.

Jastrzȩbski D, Gumola A, Gawlik R, Kozielski J. Dyspnea and quality of life in patients with pulmonary fibrosis after six weeks of respiratory rehabilitation. J Physiol Pharmacol. 2006; 57: 139–48.

Holland AE, Hill CJ, Conron M, Munro P, McDonald CF. Short term improvement in exercise capacity and symptoms following exercise training in interstitial lung disease. Thorax. 2008; 63: 549–54.

Vainshelboim B, Oliveira J, Yehoshua L, Weiss I, Fox BD, Fruchter O, et al. Exercise training-based pulmonary rehabilitation program is clinically beneficial for idiopathic pulmonary fibrosis. Respiration. 2014; 88: 378–88.

Vu Thi Thu, Hyoung Kyu Kim and JH. Models, Acute and Chronic Exercise in Animal. Adv Exp Med Biol. 2017; 1000: 55–71.

Nystoriak MA, Bhatnagar A. Cardiovascular Effects and Benefits of Exercise. Front Cardiovasc Med. 2018; 5: 1–11.

Gobatto CA, De Mello MAR, Sibuya CY, De Azevedo JRM, Dos Santos LA, Kokubun E. Maximal lactate steady state in rats submitted to swimming exercise. Comp Biochem Physiol - A Mol Integr Physiol. 2001; 130: 21–7.

Prata LO, Rodrigues CR, Martins JM, Vasconcelos PC, Oliveira FMS, Ferreira AJ, et al. Original Research: ACE2 activator associated with physical exercise potentiates the reduction of pulmonary fibrosis. Exp Biol Med. 2017; 242: 8–21.

Morse JS, Lalonde T, Xu S, Liu WR. Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV. ChemBioChem. 2020; 21: 730–8.

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020: 1–10.

Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020; 63: 457–60.

Zou Z, Yan Y, Shu Y, Gao R, Sun Y, Li X, et al. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun. 2014; 5: 1–7.

Gu H, Xie Z, Li T, Zhang S, Lai C, Zhu P, et al. Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus. Sci Rep. 2016; 6: 1–10.