The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

Curcumin Attenuates Radiation-Induced Inflammation and Fibrosis in Rat Lungs

  • Cho, Yu Ji (Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Yi, Chin Ok (Department of Anatomy, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Jeon, Byeong Tak (Department of Anatomy, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Jeong, Yi Yeong (Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Kang, Gi Mun (Department of Radiation Oncology, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Lee, Jung Eun (Department of Thoracic and Cardiovascular Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Roh, Gu Seob (Department of Anatomy, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Lee, Jong Deog (Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine)
  • Received : 2013.01.25
  • Accepted : 2013.06.05
  • Published : 2013.08.30
Download PDF
⟨ Previous Next ⟩

Abstract

A beneficial radioprotective agent has been used to treat the radiation-induced lung injury. This study was performed to investigate whether curcumin, which is known to have anti-inflammatory and antioxidant properties, could ameliorate radiation-induced pulmonary inflammation and fibrosis in irradiated lungs. Rats were given daily doses of intragastric curcumin (200 mg/kg) prior to a single irradiation and for 8 weeks after radiation. Histopathologic findings demonstrated that macrophage accumulation, interstitial edema, alveolar septal thickness, perivascular fibrosis, and collapse in radiation-treated lungs were inhibited by curcumin administration. Radiation-induced transforming growth factor-${\beta}1$ (TGF-${\beta}1$), connective tissue growth factor (CTGF) expression, and collagen accumulation were also inhibited by curcumin. Moreover, western blot analysis revealed that curcumin lowered radiation-induced increases of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), TNF receptor 1 (TNFR1), and cyclooxygenase-2 (COX-2). Curcumin also inhibited the nuclear translocation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 in radiation-treated lungs. These results indicate that long-term curcumin administration may reduce lung inflammation and fibrosis caused by radiation treatment.

Keywords

References

  1. Rothwell RI, Kelly SA, Joslin CA. Radiation pneumonitis in patients treated for breast cancer. Radiother Oncol. 1985;4: 9-14. https://doi.org/10.1016/S0167-8140(85)80056-6
  2. Tarbell NJ, Thompson L, Mauch P. Thoracic irradiation in Hodgkin's disease: disease control and long-term complications. Int J Radiat Oncol Biol Phys. 1990;18:275-281. https://doi.org/10.1016/0360-3016(90)90089-3
  3. Maasilta P, Holsti LR, Blomqvist P, Kivisaari L, Mattson K. N-acetylcysteine in combination with radiotherapy in the treatment of non-small cell lung cancer: a feasibility study. Radiother Oncol. 1992;25:192-195. https://doi.org/10.1016/0167-8140(92)90267-X
  4. Thresiamma KC, George J, Kuttan R. Protective effect of curcumin, ellagic acid and bixin on radiation induced toxicity. Indian J Exp Biol. 1996;34:845-847.
  5. Redlich CA, Rockwell S, Chung JS, Sikora AG, Kelley M, Mayne ST. Vitamin A inhibits radiation-induced pneumonitis in rats. J Nutr. 1998;128:1661-1664.
  6. Antonadou D, Petridis A, Synodinou M, Throuvalas N, Bolanos N, Veslemes M, Sagriotis A. Amifostine reduces radiochemotherapy- induced toxicities in patients with locally advanced non-small cell lung cancer. Semin Oncol. 2003;30(6 Suppl 18):2-9.
  7. Anscher MS, Kong FM, Jirtle RL. The relevanceof transforming growth factor beta 1 in pulmonary injury after radiation therapy. Lung Cancer. 1998;19:109-120. https://doi.org/10.1016/S0169-5002(97)00076-7
  8. Anscher MS, Chen L, Rabbani Z, Kang S, Larrier N, Huang H, Samulski TV, Dewhirst MW, Brizel DM, Folz RJ, Vujaskovic Z. Recent progress in defining mechanisms and potential targets for prevention of normal tissue injury after radiation therapy. Int J Radiat Oncol Biol Phys. 2005;62:255-259. https://doi.org/10.1016/j.ijrobp.2005.01.040
  9. O'Sullivan B, Levin W. Late radiation-related fibrosis: pathogenesis, manifestations, and current management. Semin Radiat Oncol. 2003;13:274-289. https://doi.org/10.1016/S1053-4296(03)00037-7
  10. Anscher MS, Thrasher B, Rabbani Z, Teicher B, Vujaskovic Z. Antitransforming growth factor-beta antibody 1D11 ameliorates normal tissue damage caused by high-dose radiation. Int J Radiat Oncol Biol Phys. 2006;65:876-881. https://doi.org/10.1016/j.ijrobp.2006.02.051
  11. Nakao S, Ogtata Y, Shimizu E, Yamazaki M, Furuyama S, Sugiya H. Tumor necrosis factor alpha (TNF-alpha)-induced prostaglandin E2 release is mediated by the activation of cyclooxygenase-2 (COX-2) transcription via NFkappaB in human gingival fibroblasts. Mol Cell Biochem. 2002;238:11-18. https://doi.org/10.1023/A:1019927616000
  12. Hallahan DE, Virudachalam S, Kuchibhotla J. Nuclearfactor kappaB dominant negative genetic constructs inhibit X-ray induction of cell adhesion molecules in the vascular endothelium. Cancer Res. 1998;58:5484-5488.
  13. Ammon HP, Wahl MA. Pharmacology of Curcuma longa. Planta Med. 1991;57:1-7. https://doi.org/10.1055/s-2006-960004
  14. Abe Y, Hashimoto S, Horie T. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res. 1999;39:41-47. https://doi.org/10.1006/phrs.1998.0404
  15. Singh S, Aggarwal BB. Activation of transcription factor NFkappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem. 1995;270:24995-25000. https://doi.org/10.1074/jbc.270.42.24995
  16. Camacho-Barquero L, Villegas I, Sánchez-Calvo JM, Talero E, Sánchez-Fidalgo S, Motilva V, Alarcón de la Lastra C. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. Int Immunopharmacol. 2007;7:333-342. https://doi.org/10.1016/j.intimp.2006.11.006
  17. Shakibaei M, John T, Schulze-Tanzil G, Lehmann I, Mobasheri A. Suppression of NF-kappaB activation by curcuminleads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase- 9 in human articular chondrocytes: Implications for the treatment of osteoarthritis. Biochem Pharmacol. 2007; 73:1434-1445. https://doi.org/10.1016/j.bcp.2007.01.005
  18. Wang SL, Li Y, Wen Y, Chen YF, Na LX, Li ST, Sun CH. Curcumin, a potential inhibitor of up-regulation of TNF-alpha and IL-6 induced by palmitate in 3T3-L1 adipocytes through NF-kappaB and JNK pathway. Biomed Environ Sci. 2009;22: 32-39. https://doi.org/10.1016/S0895-3988(09)60019-2
  19. Thresiamma KC, George J, Kuttan R. Protective effect of curcumin, ellagic acid and bixin on radiation induced genotoxicity. J Exp Clin Cancer Res. 1998;17:431-434.
  20. Bhatia AL, Sharma A, Patni S, Sharma AL. Prophylactic effect of flaxseed oil against radiation-induced hepatotoxicity in mice. Phytother Res. 2007;21:852-859. https://doi.org/10.1002/ptr.2169
  21. Lee JC, Krochak R, Blouin A, Kanterakis S, Chatterjee S, Arguiri E, Vachani A, Solomides CC, Cengel KA, Christofidou- Solomidou M. Dietary flaxseed prevents radiation-induced oxidative lung damage, inflammation and fibrosis in a mouse model of thoracic radiation injury. Cancer Biol Ther. 2009;8: 47-53. https://doi.org/10.4161/cbt.8.1.7092
  22. Lee JC, Kinniry PA, Arguiri E, Serota M, Kanterakis S, Chatterjee S, Solomides CC, Javvadi P, Koumenis C, Cengel KA, Christofidou-Solomidou M. Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice. Radiat Res. 2010;173:590-601. https://doi.org/10.1667/RR1522.1
  23. Venkatesan N, Punithavathi D, Babu M. Protection from acute and chronic lung diseases by curcumin. Adv Exp Med Biol. 2007;595:379-405. https://doi.org/10.1007/978-0-387-46401-5_17
  24. Rezvani M, Ross GA. Modification of radiation-induced acute oral mucositis in the rat. Int J Radiat Biol. 2004;80:177-182. https://doi.org/10.1080/09553000310001654693
  25. Jagetia GC, Rajanikant GK. Effect of curcumin on radiationimpaired healing of excisional wounds in mice. J Wound Care. 2004;13:107-109.
  26. Lee KH, Rhee KH. Radioprotective effect of cyclo(L-phenylalanyl- L-prolyl) on irradiated rat lung. J Microbiol Biotechnol. 2008;18:369-376.
  27. Müller JM, Ziegler-Heitbrock HW, Baeuerle PA. Nuclear factor kappa B, a mediator of lipopolysaccharide effects. Immunobiology. 1993;187:233-256. https://doi.org/10.1016/S0171-2985(11)80342-6
  28. Vergara JA, Raymond U, Thet LA. Changes in lung morphology and cell number in radiation pneumonitis and fibrosis: a quantitative ultrastructural study. Int J Radiat Oncol Biol Phys. 1987;13:723-732. https://doi.org/10.1016/0360-3016(87)90291-4
  29. Guerry-Force ML, Perkett EA, Brigham KL, Meyrick B. Early structural changes in sheep lung following thoracic irradiation. Radiat Res. 1988;114:138-153. https://doi.org/10.2307/3577151
  30. Nicholas D, Down JD. The assessment of early and late radiation injury to the mouse lung using X-ray computerised tomography. Radiother Oncol. 1985;4:253-263. https://doi.org/10.1016/S0167-8140(85)80090-6
  31. Willner J, Vordermark D, Schmidt M, Gassel A, Flentje M, Wirtz H. Secretory activity and cell cycle alteration of alveolar type II cells in the early and late phase after irradiation. Int J Radiat Oncol Biol Phys. 2003;55:617-625. https://doi.org/10.1016/S0360-3016(02)03991-3
  32. Coggle JE, Lambert BE, Moores SR. Radiation effects in the lung. Environ Health Perspect. 1986;70:261-291. https://doi.org/10.1289/ehp.8670261
  33. Morgan GW, Breit SN. Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury. Int J Radiat Oncol Biol Phys. 1995;31:361-369. https://doi.org/10.1016/0360-3016(94)00477-3
  34. Nishioka A, Ogawa Y, Mima T, Jin YJ, Sonobe H, Kariya S, Kubota K, Yoshida S, Ueno H. Histopathologic amelioration of fibroproliferative change in rat irradiated lung using soluble transforming growth factor-beta (TGF-beta) receptor mediated by adenoviral vector. Int J Radiat Oncol Biol Phys. 2004;58: 1235-1241. https://doi.org/10.1016/j.ijrobp.2003.11.006
  35. Vujaskovic Z, Marks LB, Anscher MS. The physical parameters and molecular events associated with radiation-induced lung toxicity. Semin Radiat Oncol. 2000;10:296-307. https://doi.org/10.1053/srao.2000.9424
  36. Kuroki M, Noguchi Y, Shimono M, Tomono K, Tashiro T, Obata Y, Nakayama E, Kohno S. Repression of bleomycin-induced pneumopathy by TNF. J Immunol. 2003;170:567-574.
  37. Martinet Y, Rom WN, Grotendorst GR, Martin GR, Crystal RG. Exaggerated spontaneous release of platelet-derived growth factor by alveolar macrophages from patients with idiopathic pulmonary fibrosis. N Engl J Med. 1987;317:202-209. https://doi.org/10.1056/NEJM198707233170404
  38. Vignaud JM, Allam M, Martinet N, Pech M, Plenat F, Martinet Y. Presence of platelet-derived growth factor in normal and fibrotic lung is specifically associated with interstitial macrophages, while both interstitial macrophages and alveolar epithelial cells express the c-sis proto-oncogene. Am J Respir Cell Mol Biol. 1991;5:531-538. https://doi.org/10.1165/ajrcmb/5.6.531
  39. Büttner C, Skupin A, Reimann T, Rieber EP, Unteregger G, Geyer P, Frank KH. Local production of interleukin-4 during radiation-induced pneumonitis and pulmonary fibrosis in rats: macrophages as a prominent source of interleukin-4. Am J Respir Cell Mol Biol. 1997;17:315-325. https://doi.org/10.1165/ajrcmb.17.3.2279
  40. Yi ES, Bedoya A, Lee H, Chin E, Saunders W, Kim SJ, Danielpour D, Remick DG, Yin S, Ulich TR. Radiation-induced lung injury in vivo: expression of transforming growth factorbeta precedes fibrosis. Inflammation. 1996;20:339-352. https://doi.org/10.1007/BF01486737
  41. Park KJ, Oh YT, Kil WJ, Park W, Kang SH, Chun M. Bronchoalveolar lavage findings of radiation induced lung damage in rats. J Radiat Res. 2009;50:177-182. https://doi.org/10.1269/jrr.08089
  42. Xia DH, Xi L, Xv C, Mao WD, Shen WS, Shu ZQ, Yang HZ, Dai M. The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor beta1 and tumor necrosis factor alpha. Med Oncol. 2010;27:697-701. https://doi.org/10.1007/s12032-009-9271-3
  43. Sandur SK, Deorukhkar A, Pandey MK, Pabón AM, Shentu S, Guha S, Aggarwal BB, Krishnan S. Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity. Int J Radiat Oncol Biol Phys. 2009;75:534-542. https://doi.org/10.1016/j.ijrobp.2009.06.034
  44. Charbeneau RP, Peters-Golden M. Eicosanoids: mediators and therapeutic targets in fibrotic lung disease. Clin Sci (Lond). 2005;108:479-491. https://doi.org/10.1042/CS20050012
  45. Yang HJ, Youn H, Seong KM, Yun YJ, Kim W, Kim YH, Lee JY, Kim CS, Jin YW, Youn B. Psoralidin, a dual inhibitor of COX-2 and 5-LOX, regulates ionizing radiation (IR)-induced pulmonary inflammation. Biochem Pharmacol. 2011;82:524-534. https://doi.org/10.1016/j.bcp.2011.05.027
  46. Card JW, Voltz JW, Carey MA, Bradbury JA, Degraff LM, Lih FB, Bonner JC, Morgan DL, Flake GP, Zeldin DC. Cyclooxygenase- 2deficiency exacerbates bleomycin-induced lung dysfunction but not fibrosis. Am J Respir Cell Mol Biol. 2007;37: 300-308. https://doi.org/10.1165/rcmb.2007-0057OC

Cited by

  1. Translating Curcumin to the Clinic for Lung Cancer Prevention: Evaluation of the Preclinical Evidence for Its Utility in Primary, Secondary, and Tertiary Prevention Strategies vol.350, pp.3, 2013, https://doi.org/10.1124/jpet.114.216333
  2. Curcumin Ameliorates Renal Fibrosis by Inhibiting Local Fibroblast Proliferation and Extracellular Matrix Deposition vol.126, pp.4, 2013, https://doi.org/10.1254/jphs.14173fp
  3. Curcumin-loaded nanoparticles enhance apoptotic cell death of U2OS human osteosarcoma cells through the Akt-Bad signaling pathway vol.44, pp.1, 2013, https://doi.org/10.3892/ijo.2013.2175
  4. Plant Extracts and Plant-Derived Compounds: Promising Players in Countermeasure Strategy Against Radiological Exposure: A Review vol.15, pp.6, 2014, https://doi.org/10.7314/apjcp.2014.15.6.2405
  5. Inhibitory effect of curcumin on testosterone induced benign prostatic hyperplasia rat model vol.15, pp.None, 2013, https://doi.org/10.1186/s12906-015-0825-y
  6. Atorvastatin Ameliorates Radiation-Induced Cardiac Fibrosis in Rats vol.184, pp.6, 2013, https://doi.org/10.1667/rr14075.1
  7. Clarithromycin Attenuates Radiation-Induced Lung Injury in Mice vol.10, pp.6, 2013, https://doi.org/10.1371/journal.pone.0131671
  8. Relationship and interactions of curcumin with radiation therapy vol.7, pp.3, 2013, https://doi.org/10.5306/wjco.v7.i3.275
  9. Protection against Radiotherapy-Induced Toxicity vol.5, pp.3, 2013, https://doi.org/10.3390/antiox5030022
  10. A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part III. Countermeasures under early stages of development along with ‘standard of c vol.93, pp.9, 2013, https://doi.org/10.1080/09553002.2017.1332440
  11. Subacute toxicity evaluation of KMRC011, a Toll-like receptor-5 agonist administered by intramuscular injection to rats vol.5, pp.1, 2013, https://doi.org/10.2131/fts.5.33
  12. Protective Role of Nuclear Factor-Erythroid 2-Related Factor 2 Against Radiation-Induced Lung Injury and Inflammation vol.8, pp.None, 2013, https://doi.org/10.3389/fonc.2018.00542
  13. Mechanisms of inflammatory responses to radiation and normal tissues toxicity: clinical implications vol.94, pp.4, 2013, https://doi.org/10.1080/09553002.2018.1440092
  14. Evaluating the Protective Effect of a Combination of Curcumin and Selenium-L-Methionine on Radiation Induced Dual Oxidase Upregulation vol.24, pp.4, 2013, https://doi.org/10.15171/ps.2018.48
  15. Evaluating the Radioprotective Effect of Curcumin on Rat’s Heart Tissues vol.12, pp.1, 2013, https://doi.org/10.2174/1874471011666180831101459
  16. Reactive Oxygen Species Drive Epigenetic Changes in Radiation-Induced Fibrosis vol.2019, pp.None, 2013, https://doi.org/10.1155/2019/4278658
  17. Radiation-Induced Lung Injury (RILI) vol.9, pp.None, 2013, https://doi.org/10.3389/fonc.2019.00877
  18. Curcumin as an anti‐inflammatory agent: Implications to radiotherapy and chemotherapy vol.234, pp.5, 2019, https://doi.org/10.1002/jcp.27442
  19. Curcumin Protects Against Radiotherapy-Induced Oxidative Injury to the Skin vol.14, pp.None, 2013, https://doi.org/10.2147/dddt.s265228
  20. Targets for protection and mitigation of radiation injury vol.77, pp.16, 2020, https://doi.org/10.1007/s00018-020-03479-x
  21. Curcumin as a preventive or therapeutic measure for chemotherapy and radiotherapy induced adverse reaction: A comprehensive review vol.145, pp.None, 2020, https://doi.org/10.1016/j.fct.2020.111699
  22. The Potential Effects of Curcumin on Pulmonary Fibroblasts of Idiopathic Pulmonary Fibrosis (IPF)—Approaching with Next-Generation Sequencing and Bioinformatics vol.25, pp.22, 2013, https://doi.org/10.3390/molecules25225458
  23. Protection Against Radiation-Induced Duox1 and Duox2 Upregulation in Rat's Lung Tissues by a Combination of Curcumin and L-Selenomethionine vol.16, pp.1, 2013, https://doi.org/10.5812/jjnpp.81767
  24. Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio vol.11, pp.None, 2013, https://doi.org/10.3389/fonc.2021.653621
  25. Pulmonary fibrosis: Therapeutic and mechanistic insights into the role of phytochemicals vol.47, pp.3, 2013, https://doi.org/10.1002/biof.1713
  26. The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues vol.22, pp.17, 2013, https://doi.org/10.3390/ijms22179340