Treatment of Rat Adjuvant Arthritis with Flavonoid (Detralex®), Methotrexate, and Their Combination
- 1 September 2009
- journal article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 1173 (1), 798-804
- https://doi.org/10.1111/j.1749-6632.2009.04618.x
Abstract
In both adjuvant arthritis and rheumatoid arthritis, edema and inflammation appear in synovial joints. Edema or effusion reflects an imbalance in lymph dynamics. Purified micronized flavonoid fraction is mainly used in the treatment of chronic venous insufficiency. This compound improves lymphatic drainage with a significant increase in lymphatic flow and lymphatic pulsality. It is suggested that the beneficial effect of purified micronized flavonoid fraction may be involved in the treatment of adjuvant arthritis in rats. In this study treatment of adjuvant arthritis in rats with Detralex, methotrexate, and their combination were evaluated. Groups of rats with adjuvant arthritis were treated with methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day), and their combination for 50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum albumin level, serum nitrite/nitrate concentrations, and whole-body mineral density were evaluated as markers of inflammation and destructive changes associated with arthritis. Long-term prophylactic treatment with low-dose methotrexate significantly inhibited the markers of both inflammation and arthritis. Detralex administered alone slightly decreased both the hind paw swelling and the arthritic score. Other inflammatory and arthritic markers were not significantly influenced. However, Detralex combined with methotrexate markedly potentiated the beneficial effects of methotrexate, which resulted in a more significant reduction in hind paw swelling, arthritic scores, and serum concentrations of nitrite/nitrate. Interestingly, the arthritis-induced decrease of bone mineral density in AA rats was significantly lower only in the group treated with the combination of Detralex and methotrexate. Our results indicate that Detralex increased the therapeutic efficacy of methotrexate basal treatment in AA. We suggest that this may be related to the beneficial effect of Detralex on microcirculation, especially on venules and lymphatic vessels.This publication has 19 references indexed in Scilit:
- Suppression of Collagen-Induced Arthritis by Oral Administration of theCitrusFlavonoid HesperidinPlanta Medica, 2006
- Conspicuous synovial lymphatic capillaries in juvenile idiopathic arthritis synovitis with rice bodiesAnnals Of The Rheumatic Diseases, 2005
- Methotrexate suppresses nitric oxide production ex vivo in macrophages from rats with adjuvant-induced arthritisZeitschrift für Die Gesamte Experimentelle Medizin, 1997
- Nitric oxide production during adjuvant‐induced and collagen‐induced arthritisArthritis & Rheumatism, 1996
- Elevated nitric oxide production in rheumatoid arthritis: Detection using the fasting urinary nitrate:creatinine ratioArthritis & Rheumatism, 1996
- Nitric oxide and superoxide radical are involved in both initiation and development of adjuvant arthritis in ratsLife Sciences, 1994
- Bone morphometric changes in adjuvant-induced polyarthritic osteopenia in rats: Evidence for an early bone formation defectJournal of Bone and Mineral Research, 1993
- Alteration of interleukin-1 production and the acute phase response following medication of adjuvant arthritic rats with cyclosporin-A or methotrexateInternational Journal of Immunopharmacology, 1988
- Lymphatic clearance rates in rheumatoid arthritis.Annals Of The Rheumatic Diseases, 1971
- Oedema in Rheumatoid Arthritis: Changes in the Coefficient of Capillary FiltrationBMJ, 1971