Summary
Objective:
To
investigate the effect of diacetyl rhein (DAR) on the synthesis,
turnover and composition of cartilage in an experimental model of
osteoarthritis in beagle bitches.
Design:
Osteoarthritis
was induced in mature beagle bitches by the transection of the cranial
cruciate ligament. Six animals received DAR 20 mg/kg daily for 11 weeks.
A matched group received empty capsules daily for the same period. At
11 weeks, articular cartilage was examined for the ratio of the
6:4-sulfated disaccharides of chondroitin and the tissue concentration
of hydroxyproline and glycosaminoglycan. In addition, labeling studies
were performed to estimate the effect of DAR on proteoglycan synthesis
and turnover.
Results:
DAR
had no effect on body weight or food consumption but induced a mild
diarrhea and slightly increased the incidence of vomiting. DAR tended to
reduce proteoglycan synthesis, however, DAR did reduce proteoglycan
turnover in the femoral cartilage. DAR produced changes in the
composition of the osteoarthritic cartilage that could only 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 disaccharides; DAR
reduced the ratio in tibial plateau cartilage from osteoarthritic joints
compared with untreated tissue from osteoarthritic joints. DAR showed
moderate reduction on the biosynthesis of proteoglycans. DAR also
produced a reduction in proteoglycan turnover from all anatomical areas
compared with non-treated controls in both the lateral and medial
femoral condyles.
Conclusions:
DAR
was well tolerated by the experimental animals, but did not produce
significant changes in the synthesis or turnover of proteoglycans. The
slight reduction in proteoglycan synthesis may prove to be biologically
significant after chronic dosing. 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 translate, to significant differences in
cartilage composition over an 11-week time period.
Keywords
- Diacetylrhein;
- Osteoarthritis
0 Comment:
Post a Comment