Login Register Cart 0
Generic placeholder image

Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Celecoxib A Selective COX-2 Inhibitor Mitigates Fibrosis but not Pneumonitis Following Lung Irradiation: A Histopathological Study

Author(s): Rasoul Azmoonfar, Peyman Amini, Hana Saffar, Elahe Motevaseli, Ehsan Khodamoradi, Dheyauldeen Shabeeb, Ahmed Eleojo Musa and Masoud Najafi*

Volume 15, Issue 4, 2020

Page: [351 - 357] Pages: 7

DOI: 10.2174/1574885514666191119124739

Abstract

Background: Lung is one of the radiosensitive and late responding organs, and is an important target for ionizing radiation. Radiation-induced pneumonitis and fibrosis are major consequences of lung exposure to a high dose of radiation and pose threats to the lives of exposed people. Mitigation of lung injury following an accidental radiation event or for patients with lung cancer is one of the most interesting issues in radiobiology. In the current study, we aimed to determine whether celecoxib, the most common cyclooxygenase-2 (COX-2) inhibitor, is able to mitigate pneumonitis and fibrosis following lung irradiation or not.

Materials and Methods: 20 male mice were assigned to 4 groups: control, celecoxib treatment, radiation, and radiation plus celecoxib. Irradiation was performed with a dose of 18 Gy cobalt-60 (60Co) gamma rays. Celecoxib treatment (50 mg/kg) started 24 h after irradiation and continued four times per week for 4 weeks.

Results: Irradiation of lung led to remarkable infiltration of macrophages, lymphocytes, mast cells and neutrophils. Also, a mild increase in fibrosis markers including accumulation of collagen, and alveolar and vascular thickening, was observed. Post-exposure treatment with celecoxib was able to mitigate fibrosis as well as alveolar and vascular changes, however, it was unable to mitigate pneumonitis markers.

Conclusion: Celecoxib showed that it may have an anti-fibrosis effect following exposure of mice lung to radiation, although it was unable to prevent pneumonitis.

Keywords: Radiation, celecoxib, lung, fibrosis, inflammation, pneumonitis.

« Previous Next »
Graphical Abstract

[1]
Jackson IL, Vujaskovic Z, Down JD. A further comparison of pathologies after thoracic irradiation among different mouse strains: finding the best preclinical model for evaluating therapies directed against radiation-induced lung damage. Radiat Res 2011; 175(4): 510-8.
[http://dx.doi.org/10.1667/RR2421.1] [PMID: 21338245]
[2]
Ryan JL, Krishnan S, Movsas B, Coleman CN, Vikram B, Yoo SS. Decreasing the adverse effects of cancer therapy: An NCI Workshop on the preclinical development of radiation injury mitigators/protectors Rad Res 175: 510-8.
[3]
Szabo S, Ghosh SN, Fish BL, et al. Cellular inflammatory infiltrate in pneumonitis induced by a single moderate dose of thoracic x radiation in rats. Radiat Res 2010; 173(4): 545-56.
[http://dx.doi.org/10.1667/RR1753.1] [PMID: 20334527]
[4]
Ogura A, Oowada S, Kon Y, et al. Redox regulation in radiation-induced cytochrome c release from mitochondria of human lung carcinoma A549 cells. Cancer Lett 2009; 277(1): 64-71.
[http://dx.doi.org/10.1016/j.canlet.2008.11.021] [PMID: 19117669]
[5]
Spitz DR, Azzam EI, Li JJ, Gius D. Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: A unifying concept in stress response biology. Cancer Metastasis Rev 2004; 23(3-4): 311-22.
[http://dx.doi.org/10.1023/B:CANC.0000031769.14728.bc] [PMID: 15197331]
[6]
Reiners C, Biko J, Haenscheid H, et al. Twenty-five years after Chernobyl: outcome of radioiodine treatment in children and adolescents with very high-risk radiation-induced differentiated thyroid carcinoma. J Clin Endocrinol Metab 2013; 98(7): 3039-48.
[http://dx.doi.org/10.1210/jc.2013-1059] [PMID: 23616148]
[7]
Hebestreit H, Biko J, Drozd V, et al. Pulmonary fibrosis in youth treated with radioiodine for juvenile thyroid cancer and lung metastases after Chernobyl. Eur J Nucl Med Mol Imaging 2011; 38(9): 1683-90.
[http://dx.doi.org/10.1007/s00259-011-1841-x] [PMID: 21626048]
[8]
Mahmood J, Jelveh S, Calveley V, Zaidi A, Doctrow SR, Hill RP. Mitigation of lung injury after accidental exposure to radiation. Radiat Res 2011; 176(6): 770-80.
[http://dx.doi.org/10.1667/RR2562.1] [PMID: 22013884]
[9]
Medhora M, Gao F, Fish BL, Jacobs ER, Moulder JE, Szabo A. Dose-modifying factor for captopril for mitigation of radiation injury to normal lung. J Radiat Res 2012; 53(4): 633-40.
[http://dx.doi.org/10.1093/jrr/rrs004] [PMID: 22843631]
[10]
Hatch M, Ron E, Bouville A, Zablotska L, Howe G. The Chernobyl disaster: cancer following the accident at the Chernobyl nuclear power plant. Epidemiol Rev 2005; 27: 56-66.
[http://dx.doi.org/10.1093/epirev/mxi012] [PMID: 15958427]
[11]
Gauter-Fleckenstein B, Fleckenstein K, Owzar K, et al. Early and late administration of MnTE-2-PyP5+ in mitigation and treatment of radiation-induced lung damage. Free Radic Biol Med 2010; 48(8): 1034-43.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.01.020] [PMID: 20096348]
[12]
Ding N-H, Jian Li J, Sun L-Q. Molecular mechanisms and treatment of radiation-induced lung fibrosis Curr drug Tar 2013; 14: 1347-56.
[http://dx.doi.org/10.2174/13894501113149990198]
[13]
Anscher MS, Chen L, Rabbani Z, et al. Recent progress in defining mechanisms and potential targets for prevention of normal tissue injury after radiation therapy. Int J Radiat Oncol Biol Phys 2005; 65: 255-9.
[http://dx.doi.org/10.1016/j.ijrobp.2005.01.040]
[14]
Yarnold J, Brotons MCV. Pathogenetic mechanisms in radiation fibrosis. Radiother Oncol 2010; 97(1): 149-61.
[http://dx.doi.org/10.1016/j.radonc.2010.09.002] [PMID: 20888056]
[15]
Rübe CE, Uthe D, Schmid KW, et al. Dose-dependent induction of transforming growth factor β (TGF-β) in the lung tissue of fibrosis-prone mice after thoracic irradiation. Int J Radiat Oncol Biol Phys 2000; 47: 1033-42.
[16]
Hart JP, Broadwater G, Rabbani Z, et al. Cytokine profiling for prediction of symptomatic radiation-induced lung injury. Int J Radiat Oncol Biol Phys 2005; 63: 1448-54.
[http://dx.doi.org/10.1016/j.ijrobp.2005.05.032]
[17]
Zhao Y, de Toledo SM, Hu G, Hei TK, Azzam EI. Connexins and cyclooxygenase-2 crosstalk in the expression of radiation-induced bystander effects. Br J Cancer 2014; 111(1): 125-31.
[http://dx.doi.org/10.1038/bjc.2014.276] [PMID: 24867691]
[18]
Chai Y, Calaf GM, Zhou H, et al. Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice. Br J Cancer 2013; 108(1): 91-8.
[http://dx.doi.org/10.1038/bjc.2012.498] [PMID: 23321513]
[19]
Laube M, Kniess T, Pietzsch J. Development of antioxidant COX-2 inhibitors as radioprotective agents for radiation therapy-a hypothesis-driven review. Antioxidants 2016; 5(2): 5.
[http://dx.doi.org/10.3390/antiox5020014] [PMID: 27104573]
[20]
El-Ghazaly MA, Nada AS, El-Hazek RM, Khayyal MT. Effect of selective COX-2 inhibitor, celecoxib on adjuvant-induced arthritis model in irradiated rats. Int J Radiat Biol 2010; 86(12): 1079-87.
[http://dx.doi.org/10.3109/09553002.2010.501839] [PMID: 20698743]
[21]
Khayyal MT, El-Ghazaly MA, El-Hazek RM, Nada AS. The effects of celecoxib, a COX-2 selective inhibitor, on acute inflammation induced in irradiated rats. Inflammopharmacology 2009; 17(5): 255-66.
[http://dx.doi.org/10.1007/s10787-009-0014-z] [PMID: 19798548]
[22]
Azmoonfar R, Amini P, Yahyapour R, et al. Mitigation of radiation-induced pneumonitis and lung fibrosis using alpha-lipoic acid and resveratrol. Antiinflamm Antiallergy Agents Med Chem 2020; 19(2): 149-57.
[http://dx.doi.org/10.2174/1871523018666190319144020] [PMID: 30892165]
[23]
Farhood B, Aliasgharzadeh A, Amini P, et al. Mitigation of radiation-induced lung pneumonitis and fibrosis using metformin and melatonin: a histopathological study. Medicina 2019; 55(8): 55.
[PMID: 31366142]
[24]
Niederberger E, Tegeder I, Vetter G, et al. Celecoxib loses its anti-inflammatory efficacy at high doses through activation of NF-κB. FASEB J 2001; 15: 1622-4.
[http://dx.doi.org/10.1096/fj.00-0716fje] [PMID: 11427506]
[25]
Cheki M, Yahyapour R, Farhood B, et al. COX-2 in radiotherapy: a potential target for radioprotection and radiosensitization. Curr Mol Pharmacol 2018; 11(3): 173-83.
[http://dx.doi.org/10.2174/1874467211666180219102520] [PMID: 29468988]
[26]
Liu W, Chen Y, Wang W, et al. Combination of radiation and celebrex (celecoxib) reduce mammary and lung tumor growth. Am J Clin Oncol 2003; 26(4): S103-9.
[http://dx.doi.org/10.1097/00000421-200308002-00013] [PMID: 12902866]
[27]
Christofidou-Solomidou M, Tyagi S, Tan K-S, et al. Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice. BMC Cancer 2011; 11: 269-9.
[http://dx.doi.org/10.1186/1471-2407-11-269] [PMID: 21702963]
[28]
Hui AY, Leung WK, Chan HL, et al. Effect of celecoxib on experimental liver fibrosis in rat. Liver Int 2006; 26(1): 125-36.
[http://dx.doi.org/10.1111/j.1478-3231.2005.01202.x] [PMID: 16420518]
[29]
Gore E, Bae K, Langer C, et al. Phase I/II trial of a COX-2 inhibitor with limited field radiation for intermediate prognosis patients who have locally advanced non-small-cell lung cancer: radiation therapy oncology group 0213. Clin Lung Cancer 2011; 12(2): 125-30.
[http://dx.doi.org/10.1016/j.cllc.2011.03.007] [PMID: 21550559]
[30]
Yusup G, Akutsu Y, Mutallip M, et al. A COX-2 inhibitor enhances the antitumor effects of chemotherapy and radiotherapy for esophageal squamous cell carcinoma. Int J Oncol 2014; 44(4): 1146-52.
[http://dx.doi.org/10.3892/ijo.2014.2300] [PMID: 24535229]
[31]
Chai Y, Lam RK, Calaf GM, Zhou H, Amundson S, Hei TK. Radiation-induced non-targeted response in vivo: Role of the TGFβ-TGFBR1-COX-2 signalling pathway. Br J Cancer 2013; 108(5): 1106-12.
[http://dx.doi.org/10.1038/bjc.2013.53] [PMID: 23412109]
[32]
Wang TJ, Wu CC, Chai Y, et al. Induction of non-targeted stress responses in mammary tissues by heavy ions. PLoS One 2015; 10(8)e0136307
[http://dx.doi.org/10.1371/journal.pone.0136307] [PMID: 26317641]
[33]
Hosseinimehr SJ, Fathi M, Ghasemi A, Shiadeh SN, Pourfallah TA. Celecoxib mitigates genotoxicity induced by ionizing radiation in human blood lymphocytes. Res Pharm Sci 2017; 12(1): 82-7.
[http://dx.doi.org/10.4103/1735-5362.199051] [PMID: 28255318]
[34]
Hunter NR, Valdecanas D, Liao Z, Milas L, Thames HD, Mason KA. Mitigation and treatment of radiation-induced thoracic injury with a cyclooxygenase-2 inhibitor, celecoxib. Int J Radiat Oncol Biol Phys 2013; 85(2): 472-6.
[http://dx.doi.org/10.1016/j.ijrobp.2012.04.025] [PMID: 22672748]
[35]
Liang L, Hu D, Liu W, Williams JP, Okunieff P, Ding I. Celecoxib reduces skin damage after radiation: Selective reduction of chemokine and receptor mRNA expression in irradiated skin but not in irradiated mammary tumor. Am J Clin Oncol 2003; 26(4): S114-21.
[http://dx.doi.org/10.1097/00000421-200308002-00015] [PMID: 12902868]
[36]
Chang J, Feng W, Wang Y, et al. Whole-body proton irradiation causes long-term damage to hematopoietic stem cells in mice. Radiat Res 2015; 183(2): 240-8.
[http://dx.doi.org/10.1667/RR13887.1] [PMID: 25635345]
[37]
Pazhanisamy SK, Li H, Wang Y, Batinic-Haberle I, Zhou D. NADPH oxidase inhibition attenuates total body irradiation-induced haematopoietic genomic instability. Mutagenesis 2011; 26(3): 431-5.
[http://dx.doi.org/10.1093/mutage/ger001] [PMID: 21415439]

Rights & Permissions Print Cite
Article Metrics
32
© 2024 Bentham Science Publishers | Privacy Policy