This study demonstrates that prophylactic effect of plaster and cataplasm contained ketoprofen in adjuvant arthritis therapy by X-ray. Adjuvant arthritis was induced by a single injection of Freund's complete adjuvant. Mature female Sprague-Dawley rats were designated to 3 groups such as nontreated control, plaster-treated (PT) and cataplasm-treated (CT), each of which was composed of ten animals. The PT and the CT groups showed reduced primary paw swelling, but secondary paw swelling was not affected. Bony changes were observed in all regions of the femur and tibia of the nonadjuvant-injected leg and the adjuvant-injected leg. The mean radiographic scores of the PT and the CT groups were significantly lower than those of the control group from day 0 to 7 of the experimental period (p<0.05, p<0.01). The CT rats showed reduced poly-arthritis development than the PT rats. Our results suggest that radiographic assessment of bony changes is more suitable for measuring changes in long bones such as femur or tibia than in vertebrae. The prophylactic effect of CT prominently suppressed edematous swelling and bony changes in arthritic limb compared with PT.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Arthritis, Experimental/*prevention & control ; Calcium Sulfate ; Drug Carriers/administration & dosage ; Excipients/*administration & dosage ; Female ; Freund's Adjuvant ; Ketoprofen/*administration & dosage/analogs & derivatives/therapeutic use ; Rats ; Rats, Sprague-Dawley

Nonsteroidal antiinflammatory drugs(NSAIDs) are known as clinically effective agents for treatment of inflammatory diseases. Inhibition of cyclooxygenase has been thought to be a major facet of the pharmacological mechanism of NSAIDs. However, it is difficult to ascribe the antiinflammatory effects of NSAIDs solely to the inhibition of prostaglandin synthesis. Human neutrophil elastase (HNElastase; HNE, EC 3.4.21.37) has been known as a causative factor in inflammatory diseases. To investigate the specific relationship between HNElastase inhibition and specificity of molecular structure of several NSAIDs, HNElastase was purified by Ultrogel AcA54 gel filtration, CM-Sephadex ion exchange, and HPLC (with TSK 250 column) chromatography. HNElastase was inhibited by aspirin and salicylate in a competitive manner and by naproxen, ketoprofen, phenylbutazone, and oxyphenbutazone in a partial competative manner, but not by ibuprofen and tolmetin. HNElastase-phenylbutazone-complex showed strong Raman shifts at 200, 440, 1124, 1194, 1384, 1506, and 1768 cm(-1). The Raman bands 1194, 1384, and 1768 cm(-1) may represent evidences of the conformational change at -N=N-phi radical, pyrazol ring, and -C=O radical of the elastase-drug complex, respectively. Phenylbutazone might be bound to HNElastase by ionic and hydrophobic interaction, and masked the active site. Inhibition of HNElastase could be another mechanism of action of NSAIDs besides cyclooxygenase inhibition in the treatment of inflammatory diseases. Different inhibition characteristics of HNE-lastase by NSAIDs such as aspirin, phenylbutazone-like drugs and ineffective drugs could be important points for drawing the criteria for appropriate drugs in clinical application.
Anti-Inflammatory Agents, Non-Steroidal/pharmacology* ; Chromatography, Affinity ; Computer Simulation ; Enzyme Inhibitors/pharmacology ; Human ; Isoenzymes/isolation & purification ; Isoenzymes/antagonists & inhibitors ; Ketoprofen/pharmacology ; Leukocyte Elastase/isolation & purification ; Leukocyte Elastase/antagonists & inhibitors* ; Models, Molecular ; Naproxen/pharmacology ; Phenylbutazone/analogs & derivatives ; Salicylates/pharmacology ; Spectrum Analysis, Raman