Activity of anti-inflammatory drugs on an experimental model of osteoarthritis.
Osteoarthritis was induced in the rabbit by a single intra-articular injection of 0.1 ml of a 1% solution of papain. Degeneration of the cartilage was studied 3 hours, 1, 3 and 8 days after the injection by transmission electron microscopy (TEM) and quantified by measuring the fixed charge density (FCD) and 35S incorporation into glycosaminoglycans. TEM observations of chondrocytes revealed a close correlation between the development of this experimental degenerative joint disease and human osteoarthritis. The administration of CH3-prednisolone (0.1 mg/kg on the 2nd and 5th days, i.a.), of indomethacin (1 mg/kg per day X 7, i.v.), and of catalase (50,000 IU/kg per day X 7, i.m.) modified the biochemical parameters measured 8 days after the papain injection. The corticoid potentiated the action of papain (fall in GAG content and synthesis). None of the non-steroid anti-inflammatory drugs modified the FCD. On the other hand, the increase of 35S incorporation was low after indomethacin and very high after acetylsalicylic acid. Catalase brought about an almost complete recovery of GAG content, together with an important increase in 35S incorporation. This arthropathy could be widely used in experimental pharmacology as a selective test and as a means of studying the mechanism of action of osteoarthritic drugs.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001241:Aspirin / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects / Q000648:ultrastructure; D002374:Catalase / Q000494:pharmacology; D004195:Disease Models, Animal; D006025:Glycosaminoglycans / Q000032:analysis; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008722:Methods; D008775:Methylprednisolone / Q000494:pharmacology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism; D010206:Papain / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D006025:Glycosaminoglycans; D002374:Catalase; D010206:Papain; D001241:Aspirin; D008775:Methylprednisolone; D007213:Indomethacin