Skip to main content
Top
Published in: Rheumatology International 10/2009

01-08-2009 | Original Article

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

Authors: Jana Jurcovicova, Karol Svik, Sona Scsukova, Katarina Bauerova, Jozef Rovensky, Maria Stancikova

Published in: Rheumatology International | Issue 10/2009

Login to get access

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.
Literature
3.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
4.
go back to reference 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 22:1455–1460PubMed 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 22:1455–1460PubMed
5.
go back to reference Matarese G, Di Giacomo A, Sanna V et al (2001) Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol 166:5909–5916PubMed Matarese G, Di Giacomo A, Sanna V et al (2001) Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol 166:5909–5916PubMed
7.
go back to reference 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 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
11.
go back to reference Gunaydin R, Kaya T, Atay A et al (2006) Serum leptin levels in rheumatoid arthritis and relationship with disease activity. South Med J 99:1078–1083PubMed Gunaydin R, Kaya T, Atay A et al (2006) Serum leptin levels in rheumatoid arthritis and relationship with disease activity. South Med J 99:1078–1083PubMed
12.
13.
go back to reference Clemens JW, Bruot BC (1989) Testicular dysfunction in the adjuvant-induced arthritic rat. J Androl 10:419–424PubMed Clemens JW, Bruot BC (1989) Testicular dysfunction in the adjuvant-induced arthritic rat. J Androl 10:419–424PubMed
14.
go back to reference Bruot BC, Clemens JW (1992) Regulation of testosterone production in the adjuvant-induced arthritic rats. J Androl 13:87–92PubMed Bruot BC, Clemens JW (1992) Regulation of testosterone production in the adjuvant-induced arthritic rats. J Androl 13:87–92PubMed
16.
17.
go back to reference Welles WL, Silkworth J, Oronsky AL et al (1985) Studies on the effect of low dose methotrexate on rat adjuvant arthritis. J Rheumatol 12:904–906PubMed Welles WL, Silkworth J, Oronsky AL et al (1985) Studies on the effect of low dose methotrexate on rat adjuvant arthritis. J Rheumatol 12:904–906PubMed
18.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
19.
go back to reference 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 966:232–237PubMedCrossRef 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 966:232–237PubMedCrossRef
21.
go back to reference Badri SN, Vanithakumari G, Malini T (2000) Studies on methotrexate effects on testicular steroidogenesis in rats. Endocr Res 26:247–262PubMedCrossRef Badri SN, Vanithakumari G, Malini T (2000) Studies on methotrexate effects on testicular steroidogenesis in rats. Endocr Res 26:247–262PubMedCrossRef
24.
go back to reference Veselsky L, Zelezna B, Dostál J et al (2001) Suppression of adjuvant arthritis in rats by boar seminal immunosuppressive fraction. Clin Exp Rheumatol 19:153–158PubMed Veselsky L, Zelezna B, Dostál J et al (2001) Suppression of adjuvant arthritis in rats by boar seminal immunosuppressive fraction. Clin Exp Rheumatol 19:153–158PubMed
Metadata
Title
Methotrexate treatment ameliorated testicular suppression and anorexia related leptin reduction in rats with adjuvant arthritis
Authors
Jana Jurcovicova
Karol Svik
Sona Scsukova
Katarina Bauerova
Jozef Rovensky
Maria Stancikova
Publication date
01-08-2009
Publisher
Springer-Verlag
Published in
Rheumatology International / Issue 10/2009
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-009-0838-2

Other articles of this Issue 10/2009

Rheumatology International 10/2009 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine