Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter December 14, 2019

The change of proinflammatory cytokine tumor necrosis factor α level in the use of meloxicam in rat model of osteoarthritis

  • Junaidi Khotib EMAIL logo , Naning Windi Utami , Maria Apriliani Gani and Chrismawan Ardianto

Abstract

Background

Osteoarthritis (OA) is a chronic disease in the joints. One of the proinflammatory cytokines that is thought to have a major role in the inflammatory process, the emergence of pain, and cartilage damage in OA is tumor necrosis factor α (TNF-α). Meloxicam is a nonsteroidal anti-inflammatory drug class of drugs that is relatively selective in inhibiting the activity of cyclooxygenase 2 (COX-2) formation. This study is conducted to prove the change in TNF-α level in the use of meloxicam with model in animals suffering from OA.

Methods

The OA rat model was induced with sodium monoiodoacetate intra-articularly. Rats were divided into 5 groups: negative control group, positive control group, and treatment groups with various doses of meloxicam. Hyperalgesia effect was evaluated using a warm plate test, and TNF-α level was determined using enzyme-linked immunosorbent assay.

Results

The treatment groups that received meloxicam at a dose of 1.0, 3.0, or 10.0 mg/kg body weight (BW) did not show significant differences in rat knee joint diameter (p = 0.99), but showed a significant difference in sensitivity to heat stimulation (p = 0.02) compared to the control group. Osteoarthritis rats experienced a significant reduction in TNF-α level after being given meloxicam at a dose of 10 mg/kg BW compared with the control group. This shows that the 10 mg/kg BW of meloxicam is a potential dose in reducing the TNF-α level in OA rat models.

Conclusions

Based on these data, it can be concluded that the inhibition of pain and the development of OA by meloxicam in animal models may be assigned to a decreased level of TNF-α.

Acknowledgments

The author thanks the Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Airlangga for all support during research.

  1. 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.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. 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 with No: 2.KE.50.04.2019.

References

[1] Miller RE, Miller RJ, Malfait AM. Osteoarthritis joint pain: the cytokine connection. Cytokine 2014;70:185–93.10.1016/j.cyto.2014.06.019Search in Google Scholar PubMed PubMed Central

[2] Pitcher T, Sousa-Valente J, 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

[3] Verttí RD. Biochemical markers in osteoarthritis. Int J Bone Rheumatol Res 2015;2:11–7.Search in Google Scholar

[4] Bronner F, Farach-Carson MC, editors. Bone and osteoarthritis. Vol. 4. London: Springer-Verlag; 2007.10.1007/978-1-84628-701-5Search in Google Scholar

[5] Duthey B. Priority medicines for Europe and the World. A public health approach to innovation. Vol.6. Geneva: WHO Press; 2013.Search in Google Scholar

[6] O’Neill T, Felson D. Mechanisms of osteoarthritis (OA) pain. Curr Osteoporos Rep 2018;16:611–6.10.1007/s11914-018-0477-1Search in Google Scholar PubMed PubMed Central

[7] Ministry of Health Republic of Indonesia. Basic health research (Rikesdas). Jakarta: Health Research and Development Agency Ministry of Health Republic of Indonesia, 2007.Search in Google Scholar

[8] Palazzo C, Nguyen C, Lefevre-Colau MM, Rannou F, Poiraudeau S. Risk factors and burden of osteoarthritis. Ann Phys Rehabil Med 2016;59:134–8.10.1016/j.rehab.2016.01.006Search in Google Scholar PubMed

[9] Mobasheri A, Henrotin Y. Biomarkers of osteoarthritis: a review of recent research progress on soluble biochemical markers, published patents and areas for future development. Recent Pat Biomark 2011;1:25–43.Search in Google Scholar

[10] Lee YM, Son E, Kim SH, Kim DS. Effect of Alpinia oxyphylla extract in vitro and in a monosodium iodoacetate-induced osteoarthritis rat model. Phytomedicine 2019;65:153095.10.1016/j.phymed.2019.153095Search in Google Scholar PubMed

[11] Kim JR, Yoo JJ, Kim HA. Therapeutics in osteoarthritis is based on an understanding of its molecular pathogenesis. Int J Mol Sci 2018;19:674.10.3390/ijms19030674Search in Google Scholar PubMed PubMed Central

[12] Daghestani HN, Kraus VB. Cartilage osteoarthritis. HHS Public Access 2016;23:1890–6.Search in Google Scholar

[13] Malfait A, Schnitzer T. Towards a mechanism-based approach to pain management in osteoarthritis. Nat Rev Rheumatol 2013;9:654–64.10.1038/nrrheum.2013.138Search in Google Scholar PubMed PubMed Central

[14] Ahmed M, Dinesh K, Daniel EF. Meloxicam in rheumatoid arthritis. Exp Opin Drug Metab Toxicol 2005;1:51–739.10.1517/17425255.1.4.739Search in Google Scholar PubMed

[15] Nagy E, Vajda E, Vari C, Sipka S, Fárr A, Horváth E. Meloxicam ameliorates the cartilage and subchondral bone deterioration in monoiodoacetate-induced rat osteoarthritis. Peer J 2017;5:e3185.10.7717/peerj.3185Search in Google Scholar PubMed PubMed Central

[16] Ridwan E. Ethical use of experimental animals in health research. Journal of the Indonesian Medical Association 2013;63:112–6.Search in Google Scholar

[17] Bianchi M, Panerai AE. Effects of lornoxicam, piroxicam, and meloxicam in a model of thermal hindpaw hyperalgesia induced by formalin injection in rat tails. Pharmacol Res 2002;45:101–5.10.1006/phrs.2001.0921Search in Google Scholar

[18] Gonzalez AS, Guasti AF. Ejaculation induced change in escape latency in the hot plate test: pharmacological analysis of anxiolytic versus analgesic effect. Behav Brain Res 1993;60:191–8.10.1016/0166-4328(94)90147-3Search in Google Scholar

[19] Fernihough J, Gentry C, Malcangio M, Fox A, Rediske J, Pellas T, et al. Pain related behavior in two models of osteoarthritis in the rat knee. Pain 2004;l112:83–93.10.1016/j.pain.2004.08.004Search in Google Scholar PubMed

[20] Khan HM, Ashraf M, Hashmi AS, Ahmad MU, Anjum AA. Clinical assessment of experimentally induced osteoarthritis rat models in relation to time. J Anim Plant Sci 2012;22:960–5.Search in Google Scholar

[21] Hadiwidjaja S. Effects of interleukin-1β (IL-β) and tumor necrosis factor-α (TNF-α) on dopamine in cerebral palsy. Biotechnology 2004;1:25–9.Search in Google Scholar

[22] Dahlan MS. Statistics for medicine and health: descriptive, bivariate, and multivariate equipped with applications using SPSS. Jakarta: Salemba Medika, 2013.Search in Google Scholar

[23] Jiang L, Li L, Geng C, Gong D, Jiang L, Ishikawa N, et al. Monosodium iodoacetate induces apoptosis via the mitochondrial pathway involving ROS production and caspase activation in rat chondrocytes in vitro. J Orthop Res 2012;31:364–9.10.1002/jor.22250Search in Google Scholar PubMed

[24] Zhang Y, Zeng Y. Curcumin reduces inflammation in knee osteoarthritis rats through blocking TLR4/MyD88/NF-κB signal pathway. Drug Dev Res 2019;80:353–9.10.1002/ddr.21509Search in Google Scholar PubMed

[25] Wang T, He C. Pro-inflammatory cytokines: the link between obesity and osteoarthritis. Cytokine Growth Factor Rev 2018;44:38–50.10.1016/j.cytogfr.2018.10.002Search in Google Scholar PubMed

[26] Ge H, Zou F, Li Y, Liu A, Tu M. JNK pathway in osteoarthritis: pathological and therapeutic aspects. J Recept Sig Transd 2017;37:431–6.10.1080/10799893.2017.1360353Search in Google Scholar PubMed

[27] Murray. Epidemiology of osteoarthitis from various aspects of health. Bandung: Rama Widya, 2007.Search in Google Scholar

[28] Uchida K, Takano S, Matsumoto T, Nagura N, Inoue G, Itakura M, et al. Transforming growth factor activating kinase 1 regulates extracellular matrix degrading enzymes and pain-related molecule expression following tumor necrosis factor-α stimulation of synovial cells: an in vitro study. BMC Musculoskel Dis 2017;18:1–9.10.1186/s12891-017-1648-4Search in Google Scholar PubMed PubMed Central

[29] Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003;81:646–56.Search in Google Scholar

[30] Wojdasiewicz P, Poniatowski Ł, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm 2014;2014:1–19.10.1155/2014/561459Search in Google Scholar PubMed PubMed Central

[31] Felson DT, Schaible HG. Pain in osteoarthritis. New Jersey, USA: Wiley-Blackwell, 2009.Search in Google Scholar

[32] 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

Received: 2019-11-05
Accepted: 2019-11-15
Published Online: 2019-12-14

© 2019 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 25.3.2023 from https://www.degruyter.com/document/doi/10.1515/jbcpp-2019-0331/html
Scroll Up Arrow