Effects of Oral Administration of D-002 (Beeswax Alcohols) on Histological and Functional Outcomes in a Rat Model of Antigen-Induced Arthritis: Preliminary Study

Abstract

D-002, a mixture of higher aliphatic beeswax alcohols, has been shown to display anti-inflammatory effects associated with the dual inhibition of ciclooxygenase and 5-lipoxygenase. Oral D-002 supplementation has been effective in experimental osteoarthritis, ameliorating all features of joint histopathology. Clinical studies have demonstrated that D-002 reduces osteoarthritis symptoms. However, D-002 effects on experimental models of rheumatoid arthritis (RA) have not been evaluated. To investigate whether D-002 improves histopathological and functional outcomes in a rat model of antigen-induced arthritis. First experiment. Rats were randomized into a negative vehicle-control (sham) and four groups injected with complete Freund's adjuvant (CFA): a positive vehicle-control, three treated with D-002 (50, 200 and 400 mg/kg/day) for 21 days. Second experiment. Rats were randomized into a sham and four CFA-injected groups: a positive vehicle-control, two treated with D-002 (25 and 100 mg/kg/day), one with methorexate (MTX) (0.3 mg/kg) for 28 days. Arthritis severity was evaluated by bodyweight loss, decreased exploratory activity and histological changes of tarsal joint and spleen samples in both experiments, except the exploratory activity, assessed only in the first one. CFA injection decreased the bodyweight and the exploratory activity, and induced infiltration of mononuclear cells, pannus formation and vascularity in the tarsal joint of positive control rats. These changes were significantly and markedly ameliorated by D-002 as compared to the positive control. MTX also reversed CFA-induced changes. The reduction of the infiltration of mononuclear cell with D-002 400 mg/kg was greater (80.9%) than with MTX (66.8%), but effects on other variables were similar. No abnormalities in spleen samples of D-002-treated groups were detected. This is the first report demonstrating the efficacy of oral treatment with D-002 in a rat model of antigen-induced arthritis. Results suggest that D-002 could help manage RA, but confirmation of such potential benefit requires extensive further research.