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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

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ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

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Research Article

Immunomodulatory Effects of Combined Nicotinic Acid and Prednisolone in Adjuvant-induced Arthritis

Author(s): Shadan Mirzaaghasi and Seyyed Meysam Abtahi Froushani*

Volume 22, Issue 2, 2023

Published on: 10 October, 2023

Page: [104 - 112] Pages: 9

DOI: 10.2174/0118715230264101230925060355

Price: $65

Abstract

Background: The combination of two drugs may lead to better results while reducing the need for each medication.

Objective: This study aimed to explore the synergistic benefits of combination therapy by suboptimal dose of niacin (Nic.) and prednisolone (Pred.) in an experimental model of Rheumatoid arthritis (RA).

Methods: About 50 male Wistar rats (weighing 150 - 160 grams) were randomly divided into five groups of ten, including healthy and RA groups treated with Nic. (80 mg/kg-orally), or Pred. (2 mg/kg-orally), and/or co-administration of Nic. and Pred. (half doses with each one-orally). RA was induced by the injection of complete Freund's adjuvant into the hind paw of each rat. All treatments were initiated on the fifth day following the induction and continued until day 30 post-induction.

Results: The combined Nic. and Pred. at half doses promoted a significant regression in the severity of the established RA, which is more pronounced than full doses of either drug alone. Combination therapy promoted a reduction in some hematological and biochemical RA parameters, like neutral red uptake by phagocytic cells, myeloperoxidase, nitric oxide, and C-reactive protein, more profound than each drug alone. Combined treatment caused a greater decrease in IFN-γ expression than other treatments in the area of plantar joints. All treatments were effective in increasing the expression of the IL-10 in the area of plantar joints. Prednisolone was less effective in reducing the expression of the TNF-α in the area of plantar joints than the other group.

Conclusion: This combination may be a useful approach to controlling RA.

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Graphical Abstract

[1]
Smith, M.H.; Berman, J.R. What is rheumatoid arthritis? JAMA, 2022, 327(12), 1194-1194.
[http://dx.doi.org/10.1001/jama.2022.0786] [PMID: 35315883]
[2]
Akiyama, M.; Kaneko, Y. Pathogenesis, clinical features, and treatment strategy for rheumatoid arthritis-associated interstitial lung disease. Autoimmun. Rev., 2022, 21(5), 103056.
[http://dx.doi.org/10.1016/j.autrev.2022.103056] [PMID: 35121155]
[3]
Liu, M.; Dong, J.; Yang, Y.; Yang, X.; Xu, H. Anti-inflammatory effects of triptolide loaded poly(d,l-lactic acid) nanoparticles on adjuvant-induced arthritis in rats. J. Ethnopharmacol., 2005, 97(2), 219-225.
[http://dx.doi.org/10.1016/j.jep.2004.10.031] [PMID: 15707756]
[4]
Aletaha, D.; Smolen, J.S. Diagnosis and management of rheumatoid arthritis: A review. JAMA, 2018, 320(13), 1360-1372.
[http://dx.doi.org/10.1001/jama.2018.13103] [PMID: 30285183]
[5]
Sweeney, S.E.; Firestein, G.S. Rheumatoid arthritis: Regulation of synovial inflammation. Int. J. Biochem. Cell Biol., 2004, 36(3), 372-378.
[http://dx.doi.org/10.1016/S1357-2725(03)00259-0] [PMID: 14687914]
[6]
Baecklund, E.; Iliadou, A.; Askling, J.; Ekbom, A.; Backlin, C.; Granath, F.; Catrina, A.I.; Rosenquist, R.; Feltelius, N.; Sundström, C.; Klareskog, L. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum., 2006, 54(3), 692-701.
[http://dx.doi.org/10.1002/art.21675] [PMID: 16508929]
[7]
Pincus, T.; O’Dell, J.R.; Kremer, J.M. Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arthritis: A preventive strategy. Ann. Intern. Med., 1999, 131(10), 768-774.
[http://dx.doi.org/10.7326/0003-4819-131-10-199911160-00009] [PMID: 10577301]
[8]
Harrison, S.R.; Li, D.; Jeffery, L.E.; Raza, K.; Hewison, M.; Vitamin, D. autoimmune disease and rheumatoid arthritis. Calcif. Tissue Int., 2020, 106(1), 58-75.
[http://dx.doi.org/10.1007/s00223-019-00577-2] [PMID: 31286174]
[9]
Youssefi, M.; Tafaghodi, M.; Farsiani, H.; Ghazvini, K.; Keikha, M. Helicobacter pylori infection and autoimmune diseases; Is there an association with systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis and autoimmune pancreatitis? A systematic review and meta-analysis study. J. Microbiol. Immunol. Infect., 2021, 54(3), 359-369.
[http://dx.doi.org/10.1016/j.jmii.2020.08.011] [PMID: 32891538]
[10]
Golbahari, S.; Abtahi Froushani, S.M. Synergistic benefits of Nicotine and Thymol in alleviating experimental rheumatoid arthritis. Life Sci., 2019, 239, 117037.
[http://dx.doi.org/10.1016/j.lfs.2019.117037] [PMID: 31730863]
[11]
Wu, B.J.; Yan, L.; Charlton, F.; Witting, P.; Barter, P.J.; Rye, K.A. Evidence that niacin inhibits acute vascular inflammation and improves endothelial dysfunction independent of changes in plasma lipids. Arterioscler. Thromb. Vasc. Biol., 2010, 30(5), 968-975.
[http://dx.doi.org/10.1161/ATVBAHA.109.201129] [PMID: 20167660]
[12]
Godin, A.M.; Ferreira, W.C.; Rocha, L.T.S.; Ferreira, R.G.; Paiva, A.L.L.; Merlo, L.A.; Nascimento, E.B., Jr; Bastos, L.F.S.; Coelho, M.M. Nicotinic acid induces antinociceptive and anti-inflammatory effects in different experimental models. Pharmacol. Biochem. Behav., 2012, 101(3), 493-498.
[http://dx.doi.org/10.1016/j.pbb.2012.02.012] [PMID: 22366213]
[13]
Wang, Z.; Yi, Z.; Wang, Q.; Yin, L.; Li, J.; Xie, J.; Yang, H.; Yin, Y. Effect of different levels of niacin on serum biochemical parameters, antioxidant status, cytokine levels, inflammatory gene expression and colonic microbial composition in weaned piglets. Animals., 2022, 12(21), 3018.
[http://dx.doi.org/10.3390/ani12213018] [PMID: 36359142]
[14]
Peterson, C.T.; Rodionov, D.A.; Osterman, A.L.; Peterson, S.N. B vitamins and their role in immune regulation and cancer. Nutrients, 2020, 12(11), 3380.
[http://dx.doi.org/10.3390/nu12113380] [PMID: 33158037]
[15]
Hensvold, A.; Klareskog, L. Towards prevention of autoimmune diseases: The example of rheumatoid arthritis. Eur. J. Immunol., 2021, 51(8), 1921-1933.
[http://dx.doi.org/10.1002/eji.202048952] [PMID: 34110013]
[16]
Chan, M.M.; Yang, X.; Wang, H.; Saaoud, F.; Sun, Y.; Fong, D. The microbial metabolite trimethylamine N-oxide links vascular dysfunctions and the autoimmune disease rheumatoid arthritis. Nutrients, 2019, 11(8), 1821.
[http://dx.doi.org/10.3390/nu11081821] [PMID: 31394758]
[17]
Campbell, I.K.; Bendele, A.; Smith, D.A.; Hamilton, J.A. Granulocyte-macrophage colony stimulating factor exacerbates collagen induced arthritis in mice. Ann. Rheum. Dis., 1997, 56(6), 364-368.
[http://dx.doi.org/10.1136/ard.56.6.364] [PMID: 9227165]
[18]
Pulli, B.; Ali, M.; Forghani, R.; Schob, S.; Hsieh, K.L.C.; Wojtkiewicz, G.; Linnoila, J.J.; Chen, J.W. Measuring myeloperoxidase activity in biological samples. PLoS One, 2013, 8(7), e67976.
[http://dx.doi.org/10.1371/journal.pone.0067976] [PMID: 23861842]
[19]
Bryan, N.S.; Grisham, M.B. Methods to detect nitric oxide and its metabolites in biological samples. Free Radic. Biol. Med., 2007, 43(5), 645-657.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.04.026] [PMID: 17664129]
[20]
Abtahi, F.S.M.; Abbasi, A. Conditioned medium of mesenchymal stem cells pulsed with theobromine can instruct anti-inflammatory neutrophils. Zahedan J. Res. Med. Sci., 2020, 22(2), e86967.
[http://dx.doi.org/10.5812/zjrms.86967]
[21]
Coura, C.O.; Souza, R.B.; Rodrigues, J.A.G.; Vanderlei, E.S.O.; de Araújo, I.W.F.; Ribeiro, N.A.; Frota, A.F.; Ribeiro, K.A.; Chaves, H.V.; Pereira, K.M.A.; da Cunha, R.M.S.; Bezerra, M.M.; Benevides, N.M.B. Mechanisms involved in the anti-inflammatory action of a polysulfated fraction from Gracilaria cornea in rats. PLoS One, 2015, 10(3), e0119319.
[http://dx.doi.org/10.1371/journal.pone.0119319] [PMID: 25807556]
[22]
Gottlieb, J.A.; Hill, C.S., Jr Chemotherapy of thyroid cancer with adriamycin. Experience with 30 patients. N. Engl. J. Med., 1974, 290(4), 193-197.
[http://dx.doi.org/10.1056/NEJM197401242900404] [PMID: 4808917]
[23]
Kumar, P.; Banik, S. Pharmacotherapy options in rheumatoid arthritis. Clin. Med. Insights Arthritis Musculoskelet. Disord., 2013, 6, 35-43.
[http://dx.doi.org/10.4137/CMAMD.S5558]
[24]
Weisman, M.H.; Durez, P.; Hallegua, D.; Aranda, R.; Becker, J-C.; Nuamah, I.; Vratsanos, G.; Zhou, Y.; Moreland, L.W. Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis. J. Rheumatol., 2006, 33(11), 2162-2166.
[PMID: 17014006]
[25]
Sun, W.; Sanderson, P.E.; Zheng, W. Drug combination therapy increases successful drug repositioning. Drug Discov. Today, 2016, 21(7), 1189-1195.
[http://dx.doi.org/10.1016/j.drudis.2016.05.015] [PMID: 27240777]
[26]
Galon, J.; Franchimont, D.; Hiroi, N.; Frey, G.; Boettner, A.; Ehrhart-Bornstein, M.; O’shea, J.J.; Chrousos, G.P.; Bornstein, S.R. Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells. FASEB J., 2002, 16(1), 61-71.
[http://dx.doi.org/10.1096/fj.01-0245com] [PMID: 11772937]
[27]
Kilger, E.; Weis, F.; Briegel, J.; Frey, L.; Goetz, A.E.; Reuter, D.; Nagy, A.; Schuetz, A.; Lamm, P.; Knoll, A.; Peter, K. Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery. Crit. Care Med., 2003, 31(4), 1068-1074.
[http://dx.doi.org/10.1097/01.CCM.0000059646.89546.98] [PMID: 12682474]
[28]
Hochberg, M.C.; Tracy, J.K.; Hawkins-Holt, M.; Flores, R.H. Comparison of the efficacy of the tumour necrosis factor blocking agents adalimumab, etanercept, and infliximab when added to methotrexate in patients with active rheumatoid arthritis. Ann. Rheum. Dis., 2003, 62(90002), 13ii-16.
[http://dx.doi.org/10.1136/ard.62.suppl_2.ii13] [PMID: 14532140]
[29]
Annane, D.; Sébille, V.; Charpentier, C.; Bollaert, P-E.; François, B.; Korach, J-M.; Capellier, G.; Cohen, Y.; Azoulay, E.; Troché, G.; Chaumet-Riffaud, P.; Bellissant, E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA, 2002, 288(7), 862-871.
[http://dx.doi.org/10.1001/jama.288.7.862] [PMID: 12186604]
[30]
Rich, S.S. Analytic options for asthma genetics. Clin. Exp. Allergy, 1998, 28(S1), 84-87.
[http://dx.doi.org/10.1046/j.1365-2222.1998.0280s1084.x] [PMID: 9641599]
[31]
Hawkins, G.; McMahon, A.D.; Twaddle, S.; Wood, S.F.; Ford, I.; Thomson, N.C. Stepping down inhaled corticosteroids in asthma: Randomised controlled trial. BMJ, 2003, 326(7399), 1115.
[http://dx.doi.org/10.1136/bmj.326.7399.1115] [PMID: 12763981]
[32]
Wanders, D.; Judd, R.L. Future of GPR109A agonists in the treatment of dyslipidaemia. Diabetes Obes. Metab., 2011, 13(8), 685-691.
[http://dx.doi.org/10.1111/j.1463-1326.2011.01400.x] [PMID: 21418500]
[33]
Santolla, M.F.; De Francesco, E.M.; Lappano, R.; Rosano, C.; Abonante, S.; Maggiolini, M. Niacin activates the G protein estrogen receptor (GPER)-mediated signalling. Cell. Signal., 2014, 26(7), 1466-1475.
[http://dx.doi.org/10.1016/j.cellsig.2014.03.011] [PMID: 24662263]
[34]
Romani, M.; Hofer, D.C.; Katsyuba, E.; Auwerx, J. Niacin: An old lipid drug in a new NAD+ dress. J. Lipid Res., 2019, 60(4), 741-746.
[http://dx.doi.org/10.1194/jlr.S092007] [PMID: 30782960]
[35]
Graff, E.C.; Fang, H.; Wanders, D.; Judd, R.L. Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2. Metabolism, 2016, 65(2), 102-113.
[http://dx.doi.org/10.1016/j.metabol.2015.10.001] [PMID: 26773933]
[36]
Aly, S.A.; Alganzory, H.H.; Salem, T.A. The effect of hg-polluted drinking water on the level of hormones in male rats and the potential therapeutic action of the thiosemicarbazone and antipyrine ligands and their complexes. Eur. Chem. Bull., 2016, 5(9), 390-398.
[37]
Ciriaco, M.; Ventrice, P.; Russo, G.; Scicchitano, M.; Mazzitello, G.; Scicchitano, F.; Russo, E. Corticosteroid-related central nervous system side effects. J. Pharmacol. Pharmacother., 2013, 4(S1), S94-S98.
[http://dx.doi.org/10.4103/0976-500X.120975] [PMID: 24347992]
[38]
Fairhurst, M.; Wiech, K.; Dunckley, P.; Tracey, I. Anticipatory brainstem activity predicts neural processing of pain in humans. Pain, 2007, 128(1), 101-110.
[http://dx.doi.org/10.1016/j.pain.2006.09.001] [PMID: 17070996]
[39]
Murphy, D.; Mattey, D.; Hutchinson, D. Anti-citrullinated protein antibody positive rheumatoid arthritis is primarily determined by rheumatoid factor titre and the shared epitope rather than smoking per se. PLoS One, 2017, 12(7), e0180655.
[http://dx.doi.org/10.1371/journal.pone.0180655] [PMID: 28708862]
[40]
de Siqueira, M.B.P.; da Mota, L.M.H.; Pereira Couto, S.C.; Muniz-Junqueira, M.I. Enhanced neutrophil phagocytic capacity in rheumatoid arthritis related to the autoantibodies rheumatoid factor and anti-cyclic citrullinated peptides. BMC Musculoskelet. Disord., 2015, 16(1), 159.
[http://dx.doi.org/10.1186/s12891-015-0616-0] [PMID: 26123215]
[41]
Jessee, R.; Peart, E.; Beineke, P.; Rosenberg, S.; Wingrove, J.A.; Kraus, W.E.; Huffman, K.M. Rheumatoid arthritis complicates noninvasive whole blood gene expression testing for coronary artery disease. Am. Heart J., 2017, 192, 13-18.
[http://dx.doi.org/10.1016/j.ahj.2017.06.013] [PMID: 28938959]
[42]
Epp Boschmann, S.; Goeldner, I.; Tuon, F.F.; Schiel, W.; Aoyama, F.; de Messias-Reason, I.J. Mannose-binding lectin polymorphisms and rheumatoid arthritis: A short review and meta-analysis. Mol. Immunol., 2016, 69, 77-85.
[http://dx.doi.org/10.1016/j.molimm.2015.10.010] [PMID: 26608926]
[43]
Du, H.K.; Wang, S.X.; Liu, Y.; Zhang, S.W. Effect of niacin on nitric oxide synthase expression in rat lung exposed to silica. Chin. J. Prev. Med., 2004, 38(3), 186-189.
[PMID: 15182488]
[44]
Barczyk, A.; Sozañska, E.; Trzaska, M.; Pierzchała, W. Decreased levels of myeloperoxidase in induced sputum of patients with COPD after treatment with oral glucocorticoids. Chest, 2004, 126(2), 389-393.
[http://dx.doi.org/10.1378/chest.126.2.389] [PMID: 15302722]
[45]
Doncarli, A.; Stasiuk, L.M.; Fournier, C.; Abehsira-Amar, O. Conversionin vivo from an early dominant Th0/Th1 response to a Th2 phenotype during the development of collagen-induced arthritis. Eur. J. Immunol., 1997, 27(6), 1451-1458.
[http://dx.doi.org/10.1002/eji.1830270623] [PMID: 9209498]
[46]
Mysler, E.; Psioni, C.; Tate, P.; Tate, G. Influence of corticosteroids on C-reactive protein in patients with rheumatoid arthritis. Arthritis Res. Ther., 2004, 6(3), 1-41.
[47]
Kuvin, J.T.; Dave, D.M.; Sliney, K.A.; Mooney, P.; Patel, A.R.; Kimmelstiel, C.D.; Karas, R.H. Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease. Am. J. Cardiol., 2006, 98(6), 743-745.
[http://dx.doi.org/10.1016/j.amjcard.2006.04.011] [PMID: 16950175]
[48]
Repetto, L.; Fratino, L.; Audisio, R.A.; Venturino, A.; Gianni, W.; Vercelli, M.; Parodi, S.; Dal Lago, D.; Gioia, F.; Monfardini, S.; Aapro, M.S.; Serraino, D.; Zagonel, V. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: An Italian Group for Geriatric Oncology Study. J. Clin. Oncol., 2002, 20(2), 494-502.
[http://dx.doi.org/10.1200/JCO.2002.20.2.494] [PMID: 11786579]
[49]
Jiang, H.; Lu, Q.; Xu, J.; Huo, G.; Cai, Y.; Geng, S.; Xu, H.; Zhang, J.; Li, H.; Yuan, K.; Huang, G. Sinomenine ameliorates adjuvant-induced arthritis by inhibiting the autophagy/NETosis/inflammation axis. Sci. Rep., 2023, 13(1), 3933.
[http://dx.doi.org/10.1038/s41598-023-30922-3] [PMID: 36894604]
[50]
Wallace, D.J.; Gavin, I.M.; Karpenko, O.; Barkhordar, F.; Gillis, B.S. Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: A potentially useful tool in differential diagnosis. Rheumatol. Int., 2015, 35(6), 991-996.
[http://dx.doi.org/10.1007/s00296-014-3172-2] [PMID: 25377646]

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