Retardation of articular cartilage degradation by glycosaminoglycan polysulfate, pentosan polysulfate, and DH-40J in the rat air pouch model.
The rat subcutaneous air pouch model was adapted to examine the in vivo degradation of implanted rabbit articular cartilage, both with and without induced air pouch inflammation, over a 7-day period. The effects of 3 drugs, glycosaminoglycan polysulfate (Arteparon), pentosan polysulfate (SP-54), and zinc-chelated pentosan polysulfate (DH-40J), on inflammation-induced cartilage degradation were also examined. Implanted articular cartilage from noninflamed air pouches showed a reduction in total proteoglycan (PG) content (as hexuronic acid), but not in PG extractability or aggregation, compared with cartilage maintained in tissue culture. The injection of peptone into the air pouch as an inflammogen caused an influx of leukocytes and plasma exudate and a reduction in implanted articular cartilage PG content, extractability, and aggregation, which was significantly greater than that which occurred in noninflamed air pouches. In vitro experiments demonstrated that peptone did not have a direct effect on cartilage PG degradation. Daily injection of Arteparon, SP-54, or DH-40J (10 mg/kg) into peptone-inflamed air pouches significantly increased the PG content, extractability, and aggregation in implanted articular cartilage, compared with that in cartilage from non-drug-treated control animals. The infiltration of leukocytes into the peptone-inflamed air pouches was significantly reduced by daily administration of Arteparon, 10 mg/kg. At an equivalent dose, DH-40J increased leukocyte numbers in the pouch fluid, whereas SP-54 had no significant effect on leukocyte accumulation.
Francis
D J
DJ
Department of Rheumatology, Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
Forrest
M J
MJ
Brooks
P M
PM
Ghosh
P
P
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006025:Glycosaminoglycans / Q000494:pharmacology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D010426:Pentosan Sulfuric Polyester / Q000031:analogs & derivatives / Q000494:pharmacology*; D010461:Peptones / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D006025:Glycosaminoglycans; D010461:Peptones; D011134:Polysaccharides; D011509:Proteoglycans; C059643:zinc-chelated pentosan polysulfate; C013786:A73025; D010426:Pentosan Sulfuric Polyester