EFFECT OF DIACETYL RHEIN ON THE DEVELOPMENT OF EXPERIMENTAL OSTEOARTHRITIS - A BIOCHEMICAL INVESTIGATION

Objective: To investigate the effect of diacetyl rhein (DAR) on the sy nthesis, turnover and composition of cartilage in an experimental mode l of osteoarthritis in beagle bitches. Design: Osteoarthritis was indu ced in mature beagle bitches by the transection of the cranial cruciat e ligament. Six animals received DAR 20 mg/kg daily for 11 weeks. A ma tched group received empty capsules daily for the same period. At 11 w eeks, articular cartilage was examined for the ratio of the 6:4-sulfat ed disaccharides of chondroitin and the tissue concentration of hydrox yproline and glycosaminoglycan. In addition, labeling studies were per formed to estimate the effect of DAR on proteoglycan synthesis and tur nover. Results: DAR had no effect on body weight or food consumption b ut induced a mild diarrhea and slightly increased the incidence of vom iting. DAR tended to reduce proteoglycan synthesis, however, DAR did r educe proteoglycan turnover in the femoral cartilage. DAR produced cha nges in the composition of the osteoarthritic cartilage that could onl y partly be accounted for by changes in hydration and/or swelling. In addition, it was noted that induction of osteoarthritis increased the ratio of chondroitin 6-sulfated to chondroitin 4-sulfated disaccharide s; DAR reduced the ratio in tibial plateau cartilage from osteoarthrit ic joints compared with untreated tissue from osteoarthritic joints. D AR showed moderate reduction on the biosynthesis of proteoglycans. DAR also produced a reduction in proteoglycan turnover from all anatomica l areas compared with non-treated controls in both the lateral and med ial femoral condyles. Conclusions: DAR was well tolerated by the exper imental animals, but did not produce significant changes in the synthe sis or turnover of proteoglycans. The slight reduction in proteoglycan synthesis may prove to be biologically significant after chronic dosi ng. DAR's effects on the hydroxyproline and glycosaminoglycan content suggest, however, that it must influence the swelling of cartilage and loss of glycosaminoglycan. This indicates that small changes can tran slate, to significant differences in cartilage composition over an 11- week time period.