سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Amirkhosravi, Arian, Heidari, Mahmoudreza, Karami-Mohajeri, Somayyeh, Torshabi, Maryam, Mandegary, Ali, Mehrabani, Mehrnaz. (1402). Losartan enhances the suppressive effect of pirfenidone on the bleomycin-induced epithelial-mesenchymal transition and oxidative stress in A549 cell line. , 26(8), 972-978. doi: 10.22038/ijbms.2023.68982.15035
Arian Amirkhosravi; Mahmoudreza Heidari; Somayyeh Karami-Mohajeri; Maryam Torshabi; Ali Mandegary; Mehrnaz Mehrabani. "Losartan enhances the suppressive effect of pirfenidone on the bleomycin-induced epithelial-mesenchymal transition and oxidative stress in A549 cell line". , 26, 8, 1402, 972-978. doi: 10.22038/ijbms.2023.68982.15035
Amirkhosravi, Arian, Heidari, Mahmoudreza, Karami-Mohajeri, Somayyeh, Torshabi, Maryam, Mandegary, Ali, Mehrabani, Mehrnaz. (1402). 'Losartan enhances the suppressive effect of pirfenidone on the bleomycin-induced epithelial-mesenchymal transition and oxidative stress in A549 cell line', , 26(8), pp. 972-978. doi: 10.22038/ijbms.2023.68982.15035
Amirkhosravi, Arian, Heidari, Mahmoudreza, Karami-Mohajeri, Somayyeh, Torshabi, Maryam, Mandegary, Ali, Mehrabani, Mehrnaz. Losartan enhances the suppressive effect of pirfenidone on the bleomycin-induced epithelial-mesenchymal transition and oxidative stress in A549 cell line. , 1402; 26(8): 972-978. doi: 10.22038/ijbms.2023.68982.15035

Losartan enhances the suppressive effect of pirfenidone on the bleomycin-induced epithelial-mesenchymal transition and oxidative stress in A549 cell line

Iranian Journal of Basic Medical Sciences
مقاله 16، دوره 26، شماره 8، آبان 2023، صفحه 972-978    اصل مقاله (613.21 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2023.68982.15035
نویسندگان
Arian Amirkhosravi1، 2؛ Mahmoudreza Heidari2، 3؛ Somayyeh Karami-Mohajeri2، 3؛ Maryam Torshabi4؛ Ali Mandegary* 3، 2، 5؛ Mehrnaz Mehrabani* 1
1Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
2Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
3Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
4Department of Dental Biomaterials, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5Department of Toxicology and Pharmacology, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
چکیده
Objective(s): Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease. Despite the promising anti-fibrotic effect, the toleration of pirfenidone (PFD) by the patients in full dose is low. Combination therapy is a method for enhancing the therapeutic efficiency of PFD and decreasing its dose. Therefore, the present study evaluated the effect of a combination of losartan (LOS) and PFD on oxidative stress parameters and the epithelial-mesenchymal transition (EMT) process induced by bleomycin (BLM) in human lung adenocarcinoma A549 cells. 
Materials and Methods: The non-toxic concentrations of BLM, LOS, and PFD were assessed by the MTT assay. Malondialdehyde (MDA) and anti-oxidant enzyme activity including catalase (CAT) and superoxide dismutase (SOD) were assessed after co-treatment. Migration and western blot assays were used to evaluate EMT in BLM-exposed A549 after single or combined treatments. 
Results: The combination treatment exhibited a remarkable decrease in cellular migration compared with both single and BLM-exposed groups. Furthermore, the combination treatment significantly improved cellular anti-oxidant markers compared with the BLM-treated group. Moreover, combined therapy markedly increased epithelial markers while decreasing mesenchymal markers. 
Conclusion: This in vitro study revealed that the combination of PFD with LOS might be more protective in pulmonary fibrosis (PF) than single therapy because of its greater efficacy in regulating the EMT process and oxidative stress. The current results might offer a promising therapeutic strategy for the future clinical therapy of lung fibrosis. 
کلیدواژه‌ها
Bleomycin؛ Epithelial-mesenchymal - transition؛ Idiopathic pulmonary - fibrosis؛ Losartan؛ Oxidative stress؛ Pirfenidone
مراجع
1. Hutchinson J, Fogarty A, Hubbard R, McKeever T. Global incidence and mortality of idiopathic pulmonary fibrosis: A systematic review. Eur Respir J 2015;46:795-806.
2. Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. New Eng J Med 2018;378:1811-1823.
3. Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir Res 2018;19:1-18.
4. Chung J, Huda MN, Shin Y, Han S, Akter S, Kang I, et al. Correlation between Oxidative Stress and Transforming Growth Factor-Beta in Cancers. Int J Mol Sci 2021; 22:13181.
5. Jing Y, Han Z, Zhang S, Liu Y, Wei L. Epithelial-Mesenchymal Transition in tumor microenvironment. Cell Biosci 2011;1:1-7.
6. Lancaster LH, de Andrade JA, Zibrak JD, Padilla ML, Albera C, Nathan SD, et al. Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis. Eur Respir Rev 2017;26: 170057.
7. Ferrara F, Granata G, Pelliccia C, La Porta R, Vitiello A. The added value of pirfenidone to fight inflammation and fibrotic state induced by SARS-CoV-2. Eur J Clin Pharmacol 2020;76:1615-1618.
8. Lv Q, Wang J, Xu C, Huang X, Ruan Z, Dai Y. Pirfenidone alleviates pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways. Mol Med 2020;26:1-10.
9. Pourgholamhossein F, Rasooli R, Pournamdari M, Pourgholi L, Samareh-Fekri M, Ghazi-Khansari M, et al. Pirfenidone protects against paraquat-induced lung injury and fibrosis in mice by modulation of inflammation, oxidative stress, and gene expression. Food Chem Toxicol 2018;112:39-46.
10. Dhooria S, Agarwal R, Sehgal IS, Prasad KT, Muth V, Garg M, et al. A real-world study of the dosing and tolerability of pirfenidone and its effect on survival in idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 2020;37:148-157.
11. Miller R, Muraru S, Malpartida AB, Low J, de Almeida MP, van Engelen B, Godynyuk E, Schmitz-Abecassis B, Willighagen E, Evelo C. An approach to the proposal of drug combination for cancer therapy using a pathway data connectivity approach. J Theor Comput Chem 2022;1-19.
12. Couluris M, Kinder BW, Xu P, Gross-King M, Krischer J, Panos RJ. Treatment of idiopathic pulmonary fibrosis with losartan: A pilot project. Lung 2012;190:523-527.
13. Guo F, Sun Y, Su L, Li S, Liu Z, Li J, Hu X, Li J. Losartan attenuates paraquat-induced pulmonary fibrosis in rats. Hum Exp Toxicol 2015;34:497-505.
14. Ye Z, Hu Y. TGF‑β1: Gentlemanly orchestrator in idiopathic
pulmonary fibrosis. Int J Mol Med 2021; 48:1-14.
15. Bar‐Klein G, Cacheaux LP, Kamintsky L, Prager O, Weissberg I, Schoknecht K, Cheng P, Kim SY, Wood L, Heinemann U. Losartan prevents acquired epilepsy via TGF‐β signaling suppression. Ann Neurol 2014; 75:864-875.
16. Wu M, Peng Z, Zu C, Ma J, Lu S, Zhong J, Zhang S. Losartan attenuates myocardial endothelial-to-mesenchymal transition in spontaneous hypertensive rats via inhibiting TGF-β/Smad Signaling. PLoS One 2016;11:e0155730.
17. Sikic BI, Rozencweig M, Carter SK. Bleomycin Chemotherapy. 1st ed.  Elsevier; 2016.
18. Mehrabani M, Goudarzi M, Mehrzadi S, Siahpoosh A, Mohammadi M, Khalili H, Malayeri A. Crocin: A protective natural anti-oxidant against pulmonary fibrosis induced by bleomycin. 
Pharmacol  Rep 2020;72:992-1001.
19. Liu T, Los Santos FGD, Phan SH. The bleomycin model of pulmonary fibrosis.  Fibrosis 2017; 27-42.
20. Mehrabani M, Najafi M, Kamarul T, Mansouri K, Iranpour M, Nematollahi M, et al. Deferoxamine preconditioning to restore impaired HIF‐1α‐mediated angiogenic mechanisms in adipose‐derived stem cells from STZ‐induced type 1 diabetic rats. Cell Prolif 2015;48:532-549.
21. Juybari KB, Ebrahimi G, Moghaddam MAM, Asadikaram G, Torkzadeh-Mahani M, Akbari M, Mirzamohammadi S, Karimi A, Nematollahi MH. Evaluation of serum arsenic and its effects on anti-oxidant alterations in relapsing-remitting multiple sclerosis patients. Mult Scler Relat Disord 2018;19:79-84.
22. Goth L. A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta 1991;196:143-151.
23. Magnani L, Gaydou EM, Hubaud JC. Spectrophotometric measurement of anti-oxidant properties of flavones and flavonols against superoxide anion. Anal Chim Acta 2000;411:209-216.
24. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47:469-474.
25. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54.
26. Duitman J, van den Ende T, Spek CA. Immune checkpoints as promising targets for the treatment of idiopathic pulmonary fibrosis? J Clin Med 2019;8:1547.
27. Rasooli R, Pourgholamhosein F, Kamali Y, Nabipour F, Mandegary A. Combination therapy with pirfenidone plus prednisolone ameliorates paraquat-induced pulmonary fibrosis. Inflamm 2018;41:134-142.
28. Rasooli R, Rajaian H, Pardakhty A, Mandegary A. Preference of aerosolized pirfenidone to oral intake: An experimental model of pulmonary fibrosis by paraquat. J Aerosol Med Pulm Drug Deliv 2018;31:25-32.
29. Fujiwara A, Shintani Y, Funaki S, Kawamura T, Kimura T, Minami M, et al. Pirfenidone plays a biphasic role in inhibition of epithelial-mesenchymal transition in non-small cell lung cancer. Lung Cancer. 2017;106:8-16.
30. Chang K-W, Zhang X, Lin S-C, Lin Y-C, Li C-H, Akhrymuk I, Lin S-H, Lin C-C. Atractylodin suppresses TGF-β-mediated epithelial-mesenchymal transition in alveolar epithelial cells and attenuates bleomycin-induced pulmonary fibrosis in mice. 
Int J Mol Sci 2021; 22:11152.
31. Sul OJ, Kim JH, Lee T, Seo KW, Cha HJ, Kwon B, Ahn J-J, Cho YS, Oh Y-M, Jegal Y. GSPE protects against bleomycin-induced pulmonary fibrosis in mice via ameliorating epithelial apoptosis through inhibition of oxidative stress. Oxid Med Cell Longev 2022;2022:  8200189. 
32. Karamalakova Y, Stefanov I, Georgieva E, Nikolova G. Pulmonary protein oxidation and oxidative stress modulation by lemna minor l. in progressive bleomycin-induced idiopathic pulmonary fibrosis. Anti-oxidants. 2022;11:523.
33. Yao HW, Zhu JP, Zhao MH, Lu Y. Losartan attenuates bleomycin-induced pulmonary fibrosis in rats. Respir 2006;73:236-242.
34. Margaritopoulos GA, Vasarmidi E, Antoniou KM. Pirfenidone in the treatment of idiopathic pulmonary fibrosis: an evidence-based review of its place in therapy. Core Evid 2016;11:11-12.
35. Liu D, Zhu H, Gong L, Pu S, Wu Y, Zhang W, et al. Histone deacetylases promote ER stress induced epithelial mesenchymal transition in human lung epithelial cells. Cell Physiol Biochem 2018;46:1821-1834.
36. Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial–mesenchymal transition.Nat Rev Mol Cell Biol 2014;15:178-196.
37. Di Gregorio J, Sferra R, Speca S, Vetuschi A, Dubuquoy C, Desreumaux P, et al. Role of glycogen synthase kinase-3β and PPAR-γ on epithelial-to-mesenchymal transition in DSS-induced colorectal fibrosis. PLoS One. 2017;12:e0171093.
38. Di Gregorio J, Robuffo I, Spalletta S, Giambuzzi G, De Iuliis V, Toniato E, et al. The epithelial-to-mesenchymal transition as a possible therapeutic target in fibrotic disorders. Front Cel Dev Biol 2020;8:607483.
39. Arun S, Shulin L. Vimentin as a potential molecular target in cancer therapy or vimentin, an overview and its potential as a molecular target for cancer therapy. Cell Mol Life Sci. 2011;68:3033-3046.
40. Kim WK, Kwon Y, Jang M, Park M, Kim J, Cho S, Jang DG, Lee W-B, Jung SH, Choi HJ. β-catenin activation down-regulates cell-cell junction-related genes and induces epithelial-to-mesenchymal transition in colorectal cancers. Sci Rep 2019;9:1-15.
41. Shields MA, Krantz SB, Bentrem DJ, Dangi-Garimella S, Munshi HG. Interplay between β1-integrin and Rho signaling regulates differential scattering and motility of pancreatic cancer cells by snail and Slug proteins. J Biol Chem 2012;287:6218-6229.
42. Giannoni E, Parri M, Chiarugi P. EMT and oxidative stress: a bidirectional interplay affecting tumor malignancy. Anti-oxid Redox Signal 2012;16:1248-1263.
43. Ruan H, Lv Z, Liu S, Zhang L, Huang K, Gao S, Gan W, Liu X, Zhang S, Helian K. Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the tgf-β1 signalling pathway. J Pharm Pharmacol 2020;72:44-55.
44. Kurimoto R, Ebata T, Iwasawa S, Ishiwata T, Tada Y, Tatsumi K, Takiguchi Y. Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma. Oncol Lett  2017;14:944-950.
45. Zou J, Zhou X, Ma Y, Yu R. Losartan ameliorates renal interstitial fibrosis through metabolic pathway and Smurfs-TGF-β/Smad. Biomed Pharmacother 2022;149:112931.
46. Son H, Moon A. Epithelial-mesenchymal transition and cell invasion. Toxicol Res 2010;26:245-252.
47. Gouda MM, Prabhu A, Bhandary YP. Curcumin alleviates IL‐17A‐mediated p53‐PAI‐1 expression in bleomycin‐induced alveolar basal epithelial cells. J Cell Biochem 2018; 119:2222-2230.
48. Stahnke T, Kowtharapu BS, Stachs O, Schmitz K-P, Wurm J, Wree A, Guthoff RF, Hovakimyan M. Suppression of TGF-β pathway by pirfenidone decreases extracellular matrix deposition in ocular fibroblasts in vitro. PLoS One. 2017;12:e0172592.
49. Molina-Molina M, Machahua-Huamani C, Vicens-Zygmunt V, Llatjós R, Escobar I, Sala-Llinas E, Luburich-Hernaiz P, Dorca J, Montes-Worboys A. Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells.BMC Pulm Med 2018;18:1-13.
50. Liu W-B, Wang X-P, Wu K, Zhang R-L. Effects of angiotensin II receptor antagonist, Losartan on the apoptosis, proliferation and migration of the human pancreatic stellate cells. World J Gastroenterol 2005;11:6489-6494.

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