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Methotrexate treatment ameliorated testicular suppression and anorexia related leptin reduction in rats with adjuvant arthritis

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Abstract

Methotrexate (MTX) has been frequently used in the treatment of rheumatoid arthritis (RA). However, its action on arthritis associated male hypogonadism, or anorexia related low leptin production has not yet been studied. The well-established model of human RA is rat adjuvant-induced arthritis (AA). In the present series we aimed at the evaluation of the effects of MTX on AA induced inflammatory parameters, testosterone suppression, and anorexia associated lowered leptin release. AA was induced in male Lewis rats by intradermal injection of heat killed Mycobacterium butyricum in incomplete Freund’s adjuvant in the base of the tail. Arthritic rats were treated with two doses of MTX: 0.3 and 0.5 mg/kg twice a week orally for the period of 28 days. The evaluated parameters were body mass, hind-paw swelling, arthrogram scores, serum albumin, total testosterone and leptin on days 14, 21 and 28 of AA. MTX treatment ameliorated all parameters studied dose dependently. Higher dose of MTX induced a significant reduction in the hind-paw swelling, arthritic score, and an increase in serum albumin in all examined time intervals of AA. This dose also significantly improved the suppressed testosterone and leptin levels found in arthritic rats. Prophylactic MTX treatment of rats with AA improved all inflammatory and arthritic parameters studied indicating its clear anti-inflammatory effects. The significant improvement of testosterone and leptin shows beneficial effects of MTX on reproduction and anorexia related leptin reduction during chronic AA.

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References

  1. Gordon D, Bastall GH, Thomson JA, Sturrock RD (1988) Prolonged hypogonadism in male patients with rheumatoid arthritis during flares in disease activity. Br J Rheumatol 27:440–444. doi:10.1093/rheumatology/27.6.440

    Article  PubMed  CAS  Google Scholar 

  2. Tengstrand B, Carlström K, Hafström I (2002) Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism. Rheumatology 41:285–289. doi:10.1093/rheumatology/41.3.285

    Article  PubMed  CAS  Google Scholar 

  3. Jimenez-Balderas FJ, Tapia-Serrano R, Fonseca ME et al (2001) High frequency of association of rheumatic/autoimmune diseases and untreated male hypogonadism with severe testicular dysfunction. Arthritis Res 3:362–367. doi:10.1186/ar328

    Article  PubMed  CAS  Google Scholar 

  4. Mateo L, Nolla JM, Bonnin MR, Navarro MA et al (1995) Sex hormone status and bone mineral density in men with rheumatoid arthritis. J Rheumatol 22:1455–1460

    PubMed  CAS  Google Scholar 

  5. Matarese G, Di Giacomo A, Sanna V et al (2001) Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol 166:5909–5916

    PubMed  CAS  Google Scholar 

  6. Anders HJ, Rihl M, Heufelder A et al (1999) Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis. Metabolism 48:745–748. doi:10.1016/S0026-0495(99)90174-9

    Article  PubMed  CAS  Google Scholar 

  7. Nishiya K, Nishiyama M, Chang A et al (2000) Serum leptin levels in patients with rheumatoid arthritis are correlated with body mass index. Rinsho Byori 50:524–527

    Google Scholar 

  8. Hizmetli S, Kisa M, Gokalp N et al (2007) Are plasma and synovial fluids leptin levels correlated with disease activity in rheumatoid arthritis? Rheumatol Int 27:335–338. doi:10.1007/s00296-006-0264-7

    Article  PubMed  CAS  Google Scholar 

  9. Wislowska M, Rok M, Jaszczyk B et al (2007) Serum leptin in rheumatoid arthritis. Rheumatol Int 27:947–954. doi:10.1007/s00296-007-0335-4

    Article  PubMed  CAS  Google Scholar 

  10. Popa C, Netea MG, Radstake TR et al (2005) Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann Rheum Dis 64:1195–1198. doi:10.1136/ard.2004.032243

    Article  PubMed  CAS  Google Scholar 

  11. Gunaydin R, Kaya T, Atay A et al (2006) Serum leptin levels in rheumatoid arthritis and relationship with disease activity. South Med J 99:1078–1083

    PubMed  Google Scholar 

  12. Otero M, Lago R, Gomez R et al (2006) Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 65:1198–1201. doi:10.1136/ard.2005.046540

    Article  PubMed  CAS  Google Scholar 

  13. Clemens JW, Bruot BC (1989) Testicular dysfunction in the adjuvant-induced arthritic rat. J Androl 10:419–424

    PubMed  CAS  Google Scholar 

  14. Bruot BC, Clemens JW (1992) Regulation of testosterone production in the adjuvant-induced arthritic rats. J Androl 13:87–92

    PubMed  CAS  Google Scholar 

  15. Granado M, Priego T, Martin AI et al (2005) Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats. Am J Physiol Endocrinol Metab 288:E486–E492. doi:10.1152/ajpendo.00196.2004

    Article  PubMed  CAS  Google Scholar 

  16. Stofkova A, Skurlova M, Tybitanclova K et al (2006) Relationship among nitric oxide, leptin, ACTH, corticosterone, and IL-1β, in the early and late phases of adjuvant arthritis in male Long Evans rats. Life Sci 79:2486–2491. doi:10.1016/j.lfs.2006.08.015

    Article  PubMed  CAS  Google Scholar 

  17. Welles WL, Silkworth J, Oronsky AL et al (1985) Studies on the effect of low dose methotrexate on rat adjuvant arthritis. J Rheumatol 12:904–906

    PubMed  CAS  Google Scholar 

  18. Connolly KM, Stecher VJ, Danis E et al (1988) Alteration of interleukin-1 production and the acute phase response following medication of adjuvant arthritic rats with cyclosporine-A or methotrexate. Int J Immunopharmacol 10:717–728. doi:10.1016/0192-0561(88)90025-2

    Article  PubMed  CAS  Google Scholar 

  19. Cutolo M, Sulli A, Craviotto C et al (2002) Antiproliferative-antiinflammatory effects of methotrexate and sex hormones on cultured differentiating myeloid monocytic cells (THP-1). Ann N Y Acad Sci 966:232–237

    Article  PubMed  CAS  Google Scholar 

  20. Ganesan K, Selvam R, Abhirami R et al (2008) Gender differences and protective effects of testosterone in collagen induced arthritis in rats. Rheumatol Int 28:345–353. doi:10.1007/s00296-007-0446-y

    Article  PubMed  CAS  Google Scholar 

  21. Badri SN, Vanithakumari G, Malini T (2000) Studies on methotrexate effects on testicular steroidogenesis in rats. Endocr Res 26:247–262

    Article  PubMed  CAS  Google Scholar 

  22. Gualillo O, Eiras S, Lago F et al (2000) Elevated serum leptin concentrations induced by experimental acute inflammation. Life Sci 67:2433–2441. doi:10.1016/S0024-3205(00)00827-4

    Article  PubMed  CAS  Google Scholar 

  23. Bokarewa M, Bokarew D, Hultgren O et al (2003) Leptin consumption in the inflamed joints of patients with rheumatoid arthritis. Ann Rheum Dis 62:952–956. doi:10.1136/ard.62.10.952

    Article  PubMed  CAS  Google Scholar 

  24. Veselsky L, Zelezna B, Dostál J et al (2001) Suppression of adjuvant arthritis in rats by boar seminal immunosuppressive fraction. Clin Exp Rheumatol 19:153–158

    PubMed  CAS  Google Scholar 

  25. Wauters M, Considine RV, Van Gaal LF (2000) Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol 143:293–311. doi:10.1530/eje.0.1430293

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank Mrs. Marcela Vasinova, Katarina Vandakova, Monika Vasinova and Dana Zemekova for their excellent technical assistance. This work was financed by the Agency for Supporting of Science and Research of the Slovak Republic, grant no. 21-055205, and 51-017905.

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Authors and Affiliations

  1. Institute of Experimental Endocrinology Slovak Academy of Sciences, Vlarska 3, 83306, Bratislava, Slovakia

    Jana Jurcovicova & Sona Scsukova

  2. National Institute for Rheumatic Diseases, Nabrezie I, Krasku, 921 12, Piestany, Slovakia

    Karol Svik, Jozef Rovensky & Maria Stancikova

  3. Institute of Experimental Pharmacology Slovak Academy of Science, Dubravska cesta 9, 84104, Bratislava, Slovakia

    Katarina Bauerova

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  1. Jana Jurcovicova
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  2. Karol Svik
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  3. Sona Scsukova
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  4. Katarina Bauerova
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  5. Jozef Rovensky
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  6. Maria Stancikova
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Correspondence to Maria Stancikova.

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Jurcovicova, J., Svik, K., Scsukova, S. et al. Methotrexate treatment ameliorated testicular suppression and anorexia related leptin reduction in rats with adjuvant arthritis. Rheumatol Int 29, 1187–1191 (2009). https://doi.org/10.1007/s00296-009-0838-2

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  • DOI: https://doi.org/10.1007/s00296-009-0838-2

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