[Comparison of the pharmacologic effect of diacerein and a selective COX-2 inhibitor in the mouse induced-granuloma model].
ANIMAL MODEL OF DEGENERATIVE JOIN DISEASE: A mouse model of joint disease with an induced granuloma has demonstrated that diacerein inhibits loss of hydroxyproline and proteoglycans in joint cartilage, an effect not observed with conventional nonsteroidal antiinflammatory drugs (NSAID) or with a specific inhibitor of cyclooxygenase-2 (COX-2). Specific COX-2 inhibitors could thus be beneficially combined with disease modifying osteoarthritis drugs DMOD such as diacerein. ANTIINFLAMMATORY EFFECTS OF COX-2: During the process of inflammation, COX-2 activity appears to occur at two specific time points, with a peak at 2 hours, associated with maximal activity of PGE(2) synthase (proinflammatory prostaglandin) and a second peak after 48 hours, associated with increased levels of PGD(2) and cyclopentenones (anti-inflammatory prostaglandins).


CONCLUSIONS
Treatment with NSAID or selective anti-COX-2 agents appears to have a beneficial effect during acute phases of inflammation but their use in long-term regimens appears to have less favorable effects. Use of long-action symptomatic treatments without any apparent effect on COX-2, for example diacerein, could protect against the potentially deleterious effects of COX-2 inhibition.
Colville-Nash
P R
PR
Dpt of Experimental Pathology, Arthritis Research Campaign Research Fellow, St-Bartholoomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, London.
D000818:Animals; D000880:Anthraquinones / Q000009:adverse effects / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D051379:Mice; D010003:Osteoarthritis / Q000188:drug therapy*; D011451:Prostaglandin-Endoperoxide Synthases
D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; C025292:diacerein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases