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

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• 作者：Jana Jurcovicova (1)
  Karol Svik (2)
  Sona Scsukova (1)
  Katarina Bauerova (3)
  Jozef Rovensky (2)
  Maria Stancikova (2)
  
• 关键词：Adjuvant arthritis ; Lewis rats ; Methotrexate ; Testosterone ; Leptin
• 刊名：Rheumatology International
• 出版年：2009
• 出版时间：August 2009
• 年：2009
• 卷：29
• 期：10
• 页码：1187-1191
• 全文大小：243KB
• 参考文献：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 27:440-44. doi:10.1093/rheumatology/27.6.440 CrossRef
  2. Tengstrand B, Carlstr?m K, Hafstr?m I (2002) Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism. Rheumatology 41:285-89. doi:10.1093/rheumatology/41.3.285 CrossRef
  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 3:362-67. doi:10.1186/ar328 CrossRef
  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 22:1455-460
  5. Matarese G, Di Giacomo A, Sanna V et al (2001) Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol 166:5909-916
  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 48:745-48. doi:10.1016/S0026-0495(99)90174-9 CrossRef
  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 50:524-27
  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 27:335-38. doi:10.1007/s00296-006-0264-7 CrossRef
  9. Wislowska M, Rok M, Jaszczyk B et al (2007) Serum leptin in rheumatoid arthritis. Rheumatol Int 27:947-54. doi:10.1007/s00296-007-0335-4 CrossRef
  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 64:1195-198. doi:10.1136/ard.2004.032243 CrossRef
  11. Gunaydin R, Kaya T, Atay A et al (2006) Serum leptin levels in rheumatoid arthritis and relationship with disease activity. South Med J 99:1078-083
  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 65:1198-201. doi:10.1136/ard.2005.046540 CrossRef
  13. Clemens JW, Bruot BC (1989) Testicular dysfunction in the adjuvant-induced arthritic rat. J Androl 10:419-24
  14. Bruot BC, Clemens JW (1992) Regulation of testosterone production in the adjuvant-induced arthritic rats. J Androl 13:87-2
  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 CrossRef
  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 79:2486-491. doi:10.1016/j.lfs.2006.08.015 CrossRef
  17. Welles WL, Silkworth J, Oronsky AL et al (1985) Studies on the effect of low dose methotrexate on rat adjuvant arthritis. J Rheumatol 12:904-06
  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 10:717-28. doi:10.1016/0192-0561(88)90025-2 CrossRef
  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 966:232-37 CrossRef
  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 28:345-53. doi:10.1007/s00296-007-0446-y CrossRef
  21. Badri SN, Vanithakumari G, Malini T (2000) Studies on methotrexate effects on testicular steroidogenesis in rats. Endocr Res 26:247-62 CrossRef
  22. Gualillo O, Eiras S, Lago F et al (2000) Elevated serum leptin concentrations induced by experimental acute inflammation. Life Sci 67:2433-441. doi:10.1016/S0024-3205(00)00827-4 CrossRef
  23. Bokarewa M, Bokarew D, Hultgren O et al (2003) Leptin consumption in the inflamed joints of patients with rheumatoid arthritis. Ann Rheum Dis 62:952-56. doi:10.1136/ard.62.10.952 CrossRef
  24. Veselsky L, Zelezna B, Dostál J et al (2001) Suppression of adjuvant arthritis in rats by boar seminal immunosuppressive fraction. Clin Exp Rheumatol 19:153-58
  25. Wauters M, Considine RV, Van Gaal LF (2000) Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol 143:293-11. doi:10.1530/eje.0.1430293 CrossRef
  
• 作者单位：Jana Jurcovicova (1)
  Karol Svik (2)
  Sona Scsukova (1)
  Katarina Bauerova (3)
  Jozef Rovensky (2)
  Maria Stancikova (2)
  
  1. Institute of Experimental Endocrinology Slovak Academy of Sciences, Vlarska 3, 83306, Bratislava, Slovakia
  2. National Institute for Rheumatic Diseases, Nabrezie I, Krasku, 921 12, Piestany, Slovakia
  3. Institute of Experimental Pharmacology Slovak Academy of Science, Dubravska cesta 9, 84104, Bratislava, Slovakia
  

文摘

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.