Abstract
Background
Osteoarthritis (OA) is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. The severity of this disease is always associated with increased levels of proinflammatory cytokines, which play an important role in cartilage damage, synovitis, and other damage to joint tissues. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an inflammatory state. Several studies show that cytokines, such as interleukin 1ß, have a major role in the development of inflammation that occurs in these joints. The use of glucosamine as an adjuvant to meloxicam therapy is expected to inhibit the development of inflammatory OA.
Methods
The OA model in rat was induced by single injection of intraarticular monosodium iodoacetate (MIA). The development of OA was observed for 21 days. Furthermore, the evaluation of glucosamine potency as an adjuvant of meloxicam therapy for reducing IL-1ß was done by combined treatment at a low dose of meloxicam 1 mg/kg BW with glucosamine at a dose of 125, 250, or 500 mg/kg BW orally for 28 days. Response to hyperalgesia and knee joint diameter was measured on days 0, 7, 14, 21, 28, 35, 42, and 49. IL-1ß levels were measured on day 21 and day 49 after MIA injection.
Results
MIA injection successfully induced OA as marked by a significant difference in the time of latency to heat stimulus (p < 0.01) and a significant increase in joint diameter (p < 0.01). On day 21, IL-1ß levels showed a significant decrease in MIA injection (p = 0.05). The administration of meloxicam and glucosamine did not induce significant decrease in knee joint diameter (p > 0.10), but was able to significantly increase the latency time to heat stimulus (p < 0.01). IL-1ß levels also showed a significant decrease after administering a combination of glucosamine and meloxicam (p < 0.01).
Conclusions
Taken together, the use of glucosamine as an adjuvant in meloxicam therapy may be caused by the synergistic mechanism of meloxicam for the attenuation of OA development through systemically reducing IL-1ß.
Acknowledgments
The author thanks the Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Airlangga for all supporting during the research.
Research funding: This research was funded by the Ministri of Research, Technology and Higher Education, Republic of Indonesia through a scheme of Mandate Research Grant.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Ethical approval: All experiments were performed at the Animal Research Laboratory of Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia in accordance with the guide for care and use of laboratory animal issued by National Institute of Health revised in 1985. The protocol of this reseach was approved by the Ethical Committee of Faculty of Veterinary, Universitas Airlangga.
References
[1] Parker JN, Parker PM. The official patient’s sourcebook on osteoarthritis. United States of America: ICON Health Publications, 2003:9–44.Search in Google Scholar
[2] Tanna S. Priority Medicines for Europe and the World. “A Public Health Approach to Innovation”. Update on 2004 Background Paper Background Paper 6.12 Osteoarthritis, 2013:6–9.Search in Google Scholar
[3] Melo-Florián A. IL-1 and its role in osteoarthritis. Open J Med 2011;1:1–6.Search in Google Scholar
[4] Felson DT, Schaible HG. Pain in osteoarthritis. United States of America: Wiley-Blackwell, 2009:10–27.Search in Google Scholar
[5] Maulina M. Kerusakan proteoglikan pada osteoartritis. Jurnal Ilmiah Sains, Teknologi, Ekonomi, Sosial dan Budaya, 2017;1:61–7.Search in Google Scholar
[6] Leong DJ, Choudhury M, Hirsh DM, Hardin JA, Cobelli NJ, Sun HB. Review nutraceuticals: potential for chondroprotection and molecular targeting of osteoarthritis. Int J Mol Sci 2013;14:23063–85.10.3390/ijms141123063Search in Google Scholar PubMed PubMed Central
[7] Mahajan A, Verma S, Tandon V. Osteoarthritis. J Assoc Physician India 2013;3:634–41.Search in Google Scholar
[8] Mabey T, Honsawek S. Cytokines as biochemical markers for knee osteoarthritis. World J Orthop 2015;6:95–105.10.5312/wjo.v6.i1.95Search in Google Scholar PubMed PubMed Central
[9] Michon M, Sellam J, Berenbaum F. Targeted treatment of the rheumatic siseases, 1st ed. United Kingdom: Saunders, An Imprint of Elsevier Inc, 2010:10–30.Search in Google Scholar
[10] Laine L, White WB, Rostom A, Hochberg M. COX-2 selective inhibitors in the treatment of osteoarthritis. Semin Arthritis Rheum 2008;38:165–87.10.1016/j.semarthrit.2007.10.004Search in Google Scholar PubMed
[11] Chen Y-F, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, et al. Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess. United Kingdom: Queen’s Printer and Controller of HMSO, 2008:40–52.Search in Google Scholar
[12] Smith HS, Baird W. Meloxicam and selective COX-2 inhibitors in the management of pain in the palliative care population. Am J Hosp Palliat Care 2003;20:297–306.10.1177/104990910302000413Search in Google Scholar PubMed
[13] Mutiatikum D, Rami M. Profil disolusi dan penetapan kadar tablet meloksikam inovator dan generik bermerek dengan KCKT (kromatografi cair kinerja tinggi). Buku Penelitan Kesehatan 2010;38:140–6.Search in Google Scholar
[14] Lisboa FA, Bradley MJ, Hueman MT, Schobel SA, Gaucher BJ, Styrmisdottir EL, et al. Nonsteroidal anti-inflammatory drugs may affect cytokine response and benefit healing of combat-related extremity wounds. Surgery 2017;4:1164–73.10.1016/j.surg.2016.10.011Search in Google Scholar PubMed
[15] Gregory PJ, Sperry M, Wilson F. Dietary supplements for osteoarthritis. Am Fam Physician 2008;77:177.Search in Google Scholar
[16] Wang Y, Prentice LF, Vitetta L, Wluka AE, Cicuttini FM. The effect of nutritional supplements on osteoarthritis. Altern Med Rev 2004;9:275–96.Search in Google Scholar
[17] Kucharz EJ, Kovalenko V, Szántó S, Bruyère O, Cooper C, Reginster J-Y. A review of glucosamine for knee osteoarthritis: why patented crystalline glucosamine sulfate should be differentiated from other glucosamines to maximize clinical outcomes. Curr Med Res Opin 2016;32:997–1004.10.1185/03007995.2016.1154521Search in Google Scholar PubMed
[18] Shahine EM, Elhadidi AS. Efficacy of glucosamine sulfate in lowering serum level of interleukin-1ß in symptomatic primary knee osteoarthritis: clinical and laboratory study. Alex J Med 2014;50:159–63.Search in Google Scholar
[19] Susan MN. Penggunaan Dam Penanganan Hewan Coba Rodensi Dalam Penelitian Sesuai Dengan Kesejahteraan Hewan. Bogor: Pusat Penelitian Dan Pengembangan Peternakan, 2016:5–14.Search in Google Scholar
[20] Nagy E, Vajda E, Vari C, Sipka S, Farr AM, Horvath E. Meloxicam ameliorates the cartilage and subchondral bone deterioration in monoiodoacetate-induced rat osteoarthritis. Peer J 2017;5:1–19.10.7717/peerj.3185Search in Google Scholar PubMed PubMed Central
[21] Hadiwidjaja S. Pengaruh interleukin-1ß (IL-1ß) dan tumor necrosis factor-a (TNF-a) terhadap dopamin pada cerebral palsy. Bioteknologi 2004;1:25–9.Search in Google Scholar
[22] Pitcher T, Valente JS, Malcangio M. The monoiodoacetate model of osteoarthritis pain in the mouse. J Vis Exp 2016;111:1–5.10.3791/53746Search in Google Scholar PubMed PubMed Central
[23] Puvvadi S, Subrahmanyam CV, Juturu T, Manavalan R, Valliapan K. Solubility of meloxicam in mixed solvent systems. Ethiop Pharm J 2007;25:23–8.Search in Google Scholar
[24] Seedher N, Bhatia S. Solubility enhancement of COX-2 inhibitor using various solvent systems. AAPS 2003;4:1–9.10.1208/pt040333Search in Google Scholar PubMed PubMed Central
[25] Cahyono E, Suptijah P, Wientarsih I. Development of a pressurized hydrolysis method for producing glucosamine. Asian J Agric Food Sci 2014;2:390–6.Search in Google Scholar
[26] Moilanen LJ, Hamalainen M, Nummenmaa E, Ilmarinen P, Vuolteenaho K, Nieminen RM, et al. Monosodium iodoacetate-induced inflammation and joint pain are reduced in TRPA1 deficient mice e potential role of TRPA1 in osteoarthritis. Osteoarthritis Research Society International 2015;23:2017–26.10.1016/j.joca.2015.09.008Search in Google Scholar PubMed
[27] Yamada EF, Salgueiro AF, Goulart AS, Mendes VP, Anjos BL, Folmer V, et al. Evaluation of monosodium iodoacetate dosage to induce knee osteoarthritis: relation with oxidative stress and pain. Int J Rheum Dis 2018;22:1–12.10.1111/1756-185X.13450Search in Google Scholar PubMed
[28] Orita S, Ishikawa T, Miyagi M, Ochiai N, Inoue G, Eguchi Y, et al. Pain related sensory innervation in monoiodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain. BMC Musculoskelet Disord 2011;12:1–12.10.1186/1471-2474-12-134Search in Google Scholar PubMed PubMed Central
[29] Roman-Blas JA, Castañeda S, Largo R, Herrero-Beaumont G. Glucosamine sulfate for knee osteoarthritis: science and evidence-based use. Therapy 2010;7:591–604.10.2217/thy.10.67Search in Google Scholar
[30] Zulkarnain BS, Suharjono, Suprapti B. Efek antinociceptif gaba agonis gabapentin terhadap nyeri neuropati pada hewan coba mencit. Jurnal Penelitian Medik Eksakta, 2008;7:23–30.Search in Google Scholar
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