Treatment of Rat Adjuvant Arthritis with Flavonoid (Detralex^®), Methotrexate, and Their Combination

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.

The effects of cocoa on the immune system

“…It must be added that the oral administration of some flavonoids such as quercetin and hesperidin were only able to partially reduce AA swelling (Mamani-Matsuda et al, 2006; Li et al, 2010) or only slightly decreased this chronic inflammatory model (Rovenský, 2009). However, a cocoa diet was able to reduce the oxidative stress associated with AA (Ramos-Romero et al, 2012c).…”

CD23+/CD21hi B-cell translocation and ipsilateral lymph node collapse is associated with asymmetric arthritic flare in TNF-Tg mice

“…For example, the critical role of vascular endothelial growth factor C (VEGF-C) and its receptor VEGFR-3 in the formation of new lymphatic vessels (lymphangiogenesis) opened new avenues of research [18,19]; and the dramatic changes in the pulse of efferent lymphatic vessels during the acute (five pulses per minute) and chronic (one pulse per minute) phases of the inflammatory arthritis emphasized the contribution of local variables that had previously been largely unknown [20]. Of critical importance from a translational perspective is the development of novel therapies (for example, flavonoids, VEGF-C) that specifically target lymphangiogenesis and increase lymphatic flow [21]. Equally important is the availability of new methods to assess lymph node (LN) draining function and lymphatic flow in vivo , which have the potential to serve as biomarkers of arthritic flare and response to therapy.…”

Utilization of adjuvant arthritis model for evaluation of new approaches in rheumatoid arthritis therapy focused on regulation of immune processes and oxidative stress

“…The primary beneficial effect concerned the reduction of articular edema and normalization of biochemical parameters were also reported by other authors (Cuzzocrea et al ., 2005; Kogure et al ., 2010; Rovensky et al ., 2002; 2008; 2009b). …”