Evaluation of anti-inflammatory and anti-angiogenesis effects of naloxone in the rat air pouch model of inflammation
Keywords:
Naloxone, Inflammation, Angiogenesis, Vascular Endothelial Growth Factor, Interleukin-1Abstract
Background and objective: There is increasing evidence that the nervous system is in two-way interaction with the immune system. To study the relationship between the opioid and immune systems, the anti-inflammatory effect of naloxone - an opioid receptor antagonist - in the air pouch model as an animal model of rheumatoid arthritis was studied. Methods: Sterile air (20 and 10 ml) was subcutaneously injected into the back of the animals on days 1 and 3, respectively. On the 6th day, carrageenan was injected into the pouch. Normal saline and different doses of naloxone were injected immediately, as well as 24 and 48 hours after carrageenan in the control and treatment groups, respectively. After 72 hours, granulation tissue was opened, the pouch fluid was collected to determine the volume of exudates, the concentration of Vascular Endothelial Growth Factor (VEGF) and Interleukin 1 beta (IL-1β) and count of leukocyte. Granulation tissue was extruded and weighed. To assay the angiogenesis, the granulation tissue was homogenized and centrifuged, and the supernatant was filtered by a 0.22µ filter. Hemoglobin concentration was determined by the hemoglobin kit. Results: Naloxone clearly reduced leukocyte accumulation (p<0.01), exudate volume (p<0.001), granulation tissue weight (p<0.01), and amount of angiogenesis in the granulation tissue (p<0.001). In addition, VEGF and IL-1β levels were decreased significantly (p<0.01) and (p<0.001), respectively. Conclusion: Naloxone can reduce inflammatory and angiogenesis parameters in an air pouch inflammatory model. The anti-inflammatory effect is probably related to inhibition of leukocyte accumulation due to decreased concentration of inflammatory cytokines in exudates.References
Dantzer R. Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa. Physiological reviews. 2018;98(1):477-504. PMid: 29351513 PMCid: PMC5866360 2)Blalock J. The immune system as the sixth sense. Journal of internal medicine. 2005;257(2):126-38. DOI: 10.1111/j.1365-2796.2004.01441.x PMid: 15656872 3)Tayebati SK, El-Assouad D, Ricci A, Amenta F. Immunochemical and immunocytochemical characterization of cholinergic markers in human peripheral blood lymphocytes. Journal of neuroimmunology. 2002;132(1):147-55. DOI: 10.1016/S0165-5728(02)00325-9 4)Pintér E, Pozsgai G, Hajna Z, Helyes Z, Szolcsányi J. Neuropeptide receptors as potential drug targets in the treatment of inflammatory conditions. British journal of clinical pharmacology. 2014;77(1):5-20. DOI: 10.1111/bcp.12097 PMid: 23432438 PMCid: PMC3895342 5)Pomorska DK, Gach K, Janecka A. Immunomodulatory effects of endogenous and synthetic peptides activating opioid receptors. Mini reviews in medicinal chemistry. 2014;14(14):1148-55. DOI: 10.2174/1389557515666150101095237 PMid: 25553430 6)Schneider E, Ma X, Stratz T, Mueller W, Lorenz I, Seeling W. Immunomodulatory function of the 5‐HT3 receptor antagonist tropisetron. Scandinavian journal of rheumatology. 2004;33(sup119):34-40. DOI: 10.1080/03009740410007014 7)Eteraf-Oskouei T, Akbarzadeh-Atashkhosrow A, Maghsudi M, Najafi M. Effects of salbutamol on the inflammatory parameters and angiogenesis in the rat air pouch model of inflammation. Research in pharmaceutical sciences. 2017;12(5):364-72. DOI: 10.4103/1735-5362.213981 PMid: 28974974 PMCid: PMC5615866 8)Ghadrdan E, Najafi M, Mikaily Mirak S, Eteraf-Oskouei T. Inhibitory effects of oxytocin on the inflammatory parameters and vascular endothelial growth factor (VEGF) in the rat air pouch model of inflammation. Physiology and Pharmacology. 2016;20(1):48-56. 9)Maleki-Dizaji N, Eteraf-Oskouei T, Fakhrjou A, Maljaie SH, Garjani A. The effects of 5HT3 receptor antagonist granisetron on inflammatory parameters and angiogenesis in the air-pouch model of inflammation. International immunopharmacology. 2010;10(9):1010-6. DOI: 10.1016/j.intimp.2010.05.013 PMid: 20646986 10)Dutta R, Lunzer MM, Auger JL, Akgun E, Portoghese PS, Binstadt BA. A bivalent compound targeting CCR5 and the mu opioid receptor treats inflammatory arthritis pain in mice without inducing pharmacologic tolerance. Arthritis research & therapy. 2018;20(1):154. DOI: 10.1186/s13075-018-1661-5 PMid: 30053832 PMCid: PMC6062996 11)Ninkovic J, Roy S. Role of the mu-opioid receptor in opioid modulation of immune function. Amino acids. 2013;45(1):9-24. DOI: 10.1007/s00726-011-1163-0 PMid: 22170499 PMCid: PMC3912755 12)Duarte DB, Vasko MR, Fehrenbacher JC. Models of Inflammation: Carrageenan Air Pouch. Current protocols in pharmacology. 2016;72:5.6.1-9. DOI: 10.1002/0471141755.ph0506s72 PMid: 26995549 13)Elshabrawy HA, Chen Z, Volin MV, Ravella S, Virupannavar S, Shahrara S. The pathogenic role of angiogenesis in rheumatoid arthritis. Angiogenesis. 2015;18(4):433-48. DOI: 10.1007/s10456-015-9477-2 PMid: 26198292 PMCid: PMC4879881 14)Clavel G, Valvason C, Yamaoka K, Lemeiter D, Laroche L, Boissier M-C, et al. Relationship between angiogenesis and inflammation in experimental arthritis. European cytokine network. 2006;17(3):202-10.15)Patil KR, Mahajan UB, Unger BS, Goyal SN, Belemkar S, Surana SJ, et al. Animal Models of Inflammation for Screening of Anti-inflammatory Drugs: Implications for the Discovery and Development of Phytopharmaceuticals. International journal of molecular sciences. 2019;20(18):4367. DOI: 10.3390/ijms20184367 PMid: 31491986 PMCid: PMC6770891 16)Cornwell WD, Lewis MG, Fan X, Rappaport J, Rogers TJ. Effect of chronic morphine administration on circulating T cell population dynamics in rhesus macaques. J Neuroimmunol. 2013;265(1-2):43-50. DOI: 10.1016/j.jneuroim.2013.09.013 PMid: 24090653 PMCid: PMC3852163 17)Prossin AR, Zalcman SS, Heitzeg MM, Koch AE, Campbell PL, Phan KL, et al. Dynamic interactions between plasma IL-1 family cytokines and central endogenous opioid neurotransmitter function in humans. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2015;40(3):554-65. DOI: 10.1038/npp.2014.202 PMid: 25139063 PMCid: PMC4289943 18)Paulsson JM, Moshfegh A, Dadfar E, Held C, Jacobson SH, Lundahl J. In-vivo extravasation induces the expression of interleukin 1 receptor type 1 in human neutrophils. Clinical and experimental immunology. 2012;168(1):105-12. DOI: 10.1111/j.1365-2249.2011.04548.x PMid: 22385245 PMCid: PMC3390501 19)Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 7 ed: Elsevier Health Sciences; 2012. 20)Chin PY, Dorian CL, Hutchinson MR, Olson DM, Rice KC, Moldenhauer LM, et al. Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from inflammation-induced preterm birth. Scientific reports. 2016;6:36112. DOI: 10.1038/srep36112 PMid: 27819333 PMCid: PMC5098167 21)Dinarello CA. A clinical perspective of IL-1beta as the gatekeeper of inflammation. European journal of immunology. 2011;41(5):1203-17. DOI: 10.1002/eji.201141550 PMid: 21523780 22)Morris CJ. Carrageenan-induced paw edema in the rat and mouse. Inflammation protocols. 2003:115-21. DOI: 10.1385/1-59259-374-7:115 PMid: 12769480 23)Liu T, Zhang M, Terry MH, Schroeder H, Wilson SM, Power GG, et al. Nitrite potentiates the vasodilatory signaling of S-nitrosothiols. Nitric oxide : biology and chemistry. 2018;75:60-9. DOI: 10.1016/j.niox.2018.01.011 PMid: 29428841 PMCid: PMC5861029 24)Liu B, GAO HM, WANG JY, JEOHN GH, Cooper CL, HONG JS. Role of nitric oxide in inflammation‐mediated neurodegeneration. Annals of the New York academy of sciences. 2002;962(1):318-31. DOI: 10.1111/j.1749-6632.2002.tb04077.x PMid: 12076984 25)Sato K, Komatsu N, Higashi N, Imai Y, Irimura T. Granulation tissue formation by nonspecific inflammatory agent occurs independently of macrophage galactose-type C-type lectin-1. Clinical Immunology. 2005;115(1):47-50. DOI: 10.1016/j.clim.2005.02.005 PMid: 15870020
Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS. Low-dose naltrexone therapy improves active Crohn's disease. The American journal of gastroenterology. 2007;102(4):820-8. DOI: 10.1111/j.1572-0241.2007.01045.x PMid: 17222320 27)Tani K, Shimizu T, Motoki Y, Sone S. Chemokines in synovial inflammation in rheumatoid arthritis: basic and clinical aspects. Modern rheumatology. 2002;12(2):93-9. DOI: 10.3109/s101650200017 PMid: 24383895 28)Burger E, Nishikaku A, Gameiro J, Francelin C, Camargo Z. Cytokines expressed in the granulomatous lesions in experimental Paracoccidioidomycosis: role in host protective immunity and as fungal virulence factor. J Clin Cell Immunol S. 2013;1:2. 29)Kapasi AA, Gibbons N, Mattana J, Singhal PC. Morphine stimulates mesangial cell TNF-α and nitrite production. Inflammation. 2000;24(5):463-76. DOI: 10.1023/A:1007016329300 PMid: 10921509 30)Pourpak Z, Ahmadiani A, Alebouyeh M. Involvement of interleukin-1beta in systemic morphine effects on paw oedema in a mouse model of acute inflammation. Scandinavian journal of immunology. 2004;59(3):273-7. DOI: 10.1111/j.0300-9475.2004.01396.x PMid: 15030578 31)Eteraf-Oskouei T, Mikaily Mirak S, Najafi M. Anti-Inflammatory and Anti-Angiogenesis Effects of Verapamil on Rat Air Pouch Inflammation Model. Advanced pharmaceutical bulletin. 2017;7(4):585-91. DOI: 10.15171/apb.2017.070 PMid: 29399548 PMCid: PMC5788213 32)Howdieshell TR, Webb, W. L. , Sathyanarayana, McNeil, P. L. Inhibition of inducible nitric oxide synthase results in reductions in wound vascular endothelial growth factor expression, granulation tissue formation, and local perfusion. Surgery. 2003;133(5):528-37. DOI: 10.1067/msy.2003.128 PMid: 12773981 33)Salcedo X, Medina J, Sanz-Cameno P, Garcia-Buey L, Martin-Vilchez S, Moreno-Otero R. Review article: angiogenesis soluble factors as liver disease markers. Alimentary pharmacology & therapeutics. 2005;22(1):23-30. DOI: 10.5483/BMBRep.2008.41.4.278 PMid: 18452647 34)Shibuya M. Vascular endothelial growth factor-dependent and-independent regulation of angiogenesis. BMB reports. 2008;41(4):278-86. 35)Mostafaie A, Mohammadi Motlagh H, Mansouri K. Angiogenesis and the models to study angiogenesis. Yakhteh Med J. 2010;11(4):374-81. 36)Croll SD, Ransohoff RM, Cai N, Zhang Q, Martin FJ, Wei T, et al. VEGF-mediated inflammation precedes angiogenesis in adult brain. Experimental neurology. 2004;187(2):388-402. DOI: 10.1016/j.expneurol.2004.02.010 PMid: 15144865 37)Świdrowska-Jaros J, Smolewska E. A fresh look at angiogenesis in juvenile idiopathic arthritis. Central-European journal of immunology. 2018;43(3):325-30. DOI: 10.5114/ceji.2018.80052 PMid: 30863199 PMCid: PMC6410962 38)Lunger F, Vehmas AP, Furnrohr BG, Sopper S, Wildt L, Seeber B. Opiate receptor blockade on human granulosa cells inhibits VEGF release. Reproductive biomedicine online. 2016;32(3):316-22. DOI: 10.1016/j.rbmo.2015.12.006 PMid: 26803207 39)Singleton PA, Lingen MW, Fekete MJ, Garcia JG, Moss J. Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: role of receptor transactivation. Microvascular research. 2006;72(1-2):3-11. DOI: 10.1016/j.mvr.2006.04.004 PMid: 16820176 40)Chakrabarti S, Rizvi M, Morin K, Garg R, Freedman JE. The role of CD40L and VEGF in the modulation of angiogenesis and inflammation. Vascular pharmacology. 2010;53(3):130-7. doi: 10.1016/j.vph.2010.05.003 PMid: 20546942 41)Vujic V, Stanojevic S, Dimitrijevic M. Methionine-enkephalin stimulates hydrogen peroxide and nitric oxide production in rat peritoneal macrophages: interaction of mu, delta and kappa opioid receptors. Neuroimmunomodulation. 2004;11(6):392-403. doi: 10.1159/000080150 PMid: 15467355 42)Rotelli AE, Guardia T, Juárez AO, De la Rocha NE, Pelzer LE. Comparative study of flavonoids in experimental models of inflammation. Pharmacological research. 2003;48(6):601-6. doi: 10.1016/S1043-6618(03)00225-1 43)Kubota Y. Tumor angiogenesis and anti-angiogenic therapy. The Keio journal of medicine. 2012;61(2):47-56. doi: 10.2302/kjm.61.47 PMid: 22760023 44)Zanardo V, Simbi A, Parotto M, Severino L, Carta R, Guerrini P, et al. Morphine-induced supraventricular tachycardia in near-term fetus. Italian journal of pediatrics. 2018;44(1):111. doi: 10.1186/s13052-018-0570-1 PMid: 30249290 PMCid: PMC6154430
Published
Issue
Section
License
Copyright (c) 2020 Knowledge Kingdom Publishing
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
