BASIC FIBROBLAST GROWTH FACTOR AND ADIPONECTIN IN ADOLESCENCE WITH JUVENILE IDIOPATHIC ARTHRITIS TREATED WITH METHOTREXATE
- 1. Kharkiv Medical academy of postgraduate education
Description
Methotrexate has been applied clinically for juvenile idiopathic arthritis (JIA) treatment for decades. It is recommended for use globally, according all modern guidelines. Despite the fact that fibrosis molecular mechanisms as well as methotrexate (MTX) elimination and fibrosis indexes were studied a lot there is still not enough information for adolescence. Adiponectin, fibroblast growth factor and fibrosis indexes in adolescents with JIA treated with methotrexate were studied in this work.
The aim was to study dynamics of molecular-cellular mechanisms activation of fibrotic processes development in the liver in adolescents with juvenile idiopathic arthritis treated with methotrexate.
Materials and methods: A total of 68 children with juvenile idiopathic arthritis, were enrolled in the study. 25 boys (36.8 %) and 43 girls (63.2 %) were examined. Children were divided into three groups in accordance with the methotrexate dose. The following data were analyzed: ESR (mm/hour), C-reactive protein (mg/l), Hemolytic activity (CU), circulating immune complexes, (g/l), ALT (U/l), AST (U/l), Adiponectin (mcg/ml), BFGF (pg/ml), APRI index, FIB-4 Score.
Results: According to our results when patients start using MTX they have significantly positive effect. Therefore, when analyzing all parameters liver pathologies may occur before MTX use. When MTX used, its proinflammation and antifibrotic effects lead to normalization of all organs and systems, as well as joints and liver. Also, long-term MTX use can lead to adverse effects.
Conclusions: So, it is important to control possible liver disorders in adolescence treated with MTX. According to our study results we find out that there are decreasing of liver damage parameters in patients which started using MTX.
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References
- Smolen, J. S., Landewé, R., Bijlsma, J., Burmester, G., Chatzidionysiou, K., Dougados, M. et. al. (2017). EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Annals of the Rheumatic Diseases, 76 (6), 960–977. doi: http://doi.org/10.1136/annrheumdis-2016-210715
- Desmoulin, S. K., Hou, Z., Gangjee, A., Matherly, L. H. (2012). The human proton-coupled folate transporter. Cancer Biology & Therapy, 13 (14), 1355–1373. doi: http://doi.org/10.4161/cbt.22020
- Grim, J., Chládek, J., Martínková, J. (2003). Pharmacokinetics and Pharmacodynamics of Methotrexate in Non-Neoplastic Diseases. Clinical Pharmacokinetics, 42 (2), 139–151. doi: http://doi.org/10.2165/00003088-200342020-00003
- Herman, R. A., Veng-Pedersen, P., Hoffman, J., Koehnke, R., Furst, D. E. (1989). Pharmacokinetics of Low-Dose Methotrexate in Rheumatoid Arthritis Patients. Journal of Pharmaceutical Sciences, 78 (2), 165–171. doi: http://doi.org/10.1002/jps.2600780219
- Goodman, S. M., Cronstein, B. N., Bykerk, V. P. (2015). Outcomes Related to Methotrexate Dose and Route of Administration in Patients with Rheumatoid Arthritis: A Systematic Literature Review. Clinical and Experimental Rheumatology, 33, 272–278.
- Seideman, P., Beck, O., Eksborg, S., Wennberg, M. (1993). The pharmacokinetics of methotrexate and its 7-hydroxy metabolite in patients with rheumatoid arthritis. British Journal of Clinical Pharmacology, 35 (4), 409–412. doi: http://doi.org/10.1111/j.1365-2125.1993.tb04158.x
- Inoue, K., Yuasa, H. (2014). Molecular Basis for Pharmacokinetics and Pharmacodynamics of Methotrexate in Rheumatoid Arthritis Therapy. Drug Metabolism and Pharmacokinetics, 29 (1), 12–19. doi: http://doi.org/10.2133/dmpk.dmpk-13-rv-119
- Conway, R., Carey, J. J. (2017). Risk of liver disease in methotrexate treated patients. World Journal of Hepatology, 9 (26), 1092–1100. doi: http://doi.org/10.4254/wjh.v9.i26.1092
- Kremer, J. M., Galivan, J., Streckfuss, A., Kamen, B. (1986). Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients: Association with hepatic folate deficiency and formation of polyglutamates. Arthritis & Rheumatism, 29 (7), 832–835. doi: http://doi.org/10.1002/art.1780290703
- Prey, S., Paul, C. (2009). Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. British Journal of Dermatology, 160 (3), 622–628. doi: http://doi.org/10.1111/j.1365-2133.2008.08876.x
- Chan, E. S. L., Montesinos, M. C., Fernandez, P., Desai, A., Delano, D. L., Yee, H. et. al. (2006). Adenosine A2Areceptors play a role in the pathogenesis of hepatic cirrhosis. British Journal of Pharmacology, 148 (8), 1144–1155. doi: http://doi.org/10.1038/sj.bjp.0706812
- Che, J., Chan, E. S. L., Cronstein, B. N. (2007). Adenosine A2A Receptor Occupancy Stimulates Collagen Expression by Hepatic Stellate Cells via Pathways Involving Protein Kinase A, Src, and Extracellular Signal-Regulated Kinases 1/2 Signaling Cascade or p38 Mitogen-Activated Protein Kinase Signaling Pathway. Molecular Pharmacology, 72 (6), 1626–1636. doi: http://doi.org/10.1124/mol.107.038760
- Ortega-Alonso, A., Andrade, R. J. (2018). Chronic liver injury induced by drugs and toxins. Journal of Digestive Diseases, 19 (9), 514–521. doi: http://doi.org/10.1111/1751-2980.12612
- Vardi, N., Parlakpinar, H., Cetin, A., Erdogan, A., Cetin Ozturk, I. (2010). Protective Effect of β-Carotene on Methotrexate–Induced Oxidative Liver Damage. Toxicologic Pathology, 38 (4), 592–597. doi: http://doi.org/10.1177/0192623310367806
- Nunes, Q. M., Li, Y., Sun, C., Kinnunen, T. K., Fernig, D. G. (2016). Fibroblast growth factors as tissue repair and regeneration therapeutics. PeerJ, 4, e1535. doi: http://doi.org/10.7717/peerj.1535
- Maddaluno, L., Urwyler, C., Werner, S. (2017). Fibroblast growth factors: key players in regeneration and tissue repair. Development, 144 (22), 4047–4060. doi: http://doi.org/10.1242/dev.152587
- Tsai, S.-J., Chen, T.-M., Chen, Y.-H., Sun, Hs. (2019). Fibroblast growth factors: Potential novel targets for regenerative therapy of osteoarthritis. Chinese Journal of Physiology, 62 (1), 2. doi: http://doi.org/10.4103/cjp.cjp_11_19
- Ren, X., Zhao, M., Lash, B., Martino, M. M., Julier, Z. (2020). Growth Factor Engineering Strategies for Regenerative Medicine Applications. Frontiers in Bioengineering and Biotechnology, 7. doi: http://doi.org/10.3389/fbioe.2019.00469
- Kang, J., Hu, J., Karra, R., Dickson, A. L., Tornini, V. A., Nachtrab, G. et. al. (2016). Modulation of tissue repair by regeneration enhancer elements. Nature, 532 (7598), 201–206. doi: http://doi.org/10.1038/nature17644
- Hou, J., Kan, M., McKeehan, K., McBride, G., Adams, P., McKeehan, W. (1991). Fibroblast growth factor receptors from liver vary in three structural domains. Science, 251 (4994), 665–668. doi: http://doi.org/10.1126/science.1846977
- Kan, M., Huang, J. S., Mansson, P. E., Yasumitsu, H., Carr, B., McKeehan, W. L. (1989). Heparin-binding growth factor type 1 (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration. Proceedings of the National Academy of Sciences, 86 (19), 7432–7436. doi: http://doi.org/10.1073/pnas.86.19.7432