ABSTRACT
The sensitization of inflamed knee tissues with endogenous porphyrins was studied by means of fluorescence spectroscopy in an experimental model of rabbit rheumatoid monoarthritis after intraarticular (i.a.) or intravenous (i.v.) injections of 5-aminolevulinic acid (ALA) or ALA methyl ester (ALA-Me). Fluorescence measurements in vivo on the skin of the inflamed knee joint showed the dominance of protoporphyrin IX (PpIX). The highest fluorescence intensity was registered 2h after i.a. injection of ALA and ALA-Me. Comparative analysis of the PpIX fluorescence spectra ex vivo revealed that more PpIX accumulated in the tissues of the inflamed joint than in the tissues of the control joint, and that ALA-Me induced about five times more PpIX in the inflamed synovium than ALA. Meanwhile, the cartilages of the inflamed and control knee joints also accumulated water-soluble porphyrins. Thus, in vivo and ex vivo spectroscopic assessment of endogenous porphyrins in rabbit rheumatoid arthritis tissues implied that the injection of ALA is more appropriate for the diagnostics of inflammation due to the higher PpIX fluorescence intensity on the skin surface, while ALA-Me is more appropriate for the therapeutic applications due to the higher and more selective accumulation of PpIX in the inflamed synovium.
Subject(s)
Aminolevulinic Acid/analogs & derivatives , Aminolevulinic Acid/pharmacology , Arthritis, Rheumatoid/drug therapy , Porphyrins/analysis , Spectrometry, Fluorescence/methods , Animals , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/metabolism , Cartilage/metabolism , Disease Models, Animal , Joints/drug effects , Joints/metabolism , Porphyrins/metabolism , Rabbits , Synovial Membrane/drug effects , Synovial Membrane/metabolismABSTRACT
Rat adjuvant arthritis (AA), a model of chronic inflammation and an experimental model of rheumatoid arthritis (RA) has been used to evaluate the possible anti-inflammatory action of seventeen N,O-acil-threo-DL-phenylserines 1-17. For this purpose experiments on 200 male Wistar rats were performed. The obtained results showed that oral administration of all compounds, except 15, inhibited the development of AA as compared with the control group. Although the level of arthritic suppression of some preparations was equivalent to aspirin or exceeded it (compounds 2-4, 6, 10, 13), only the preparation 10 in a dose of 100 mg/kg significantly change the paw swelling (P < 0.02) which decreased by 27.9-31.7% at the end of experiment. Pronounced inhibition (P < 0.05-0.01) of joint swelling and the indices of pathological process activity were revealed in earlier stages of AA under the treatment with compounds such as 6 and 11. The antiinflammatory effect of some compounds (9, 11, 13) was observed in the middle of the experiment, although only compound 9 showed significant suppression by 35.9-37.9% at this stage (P < 0.01-0.001) which also markedly decreased ESR (P < 0.05). The latter index was significantly reduced by the action of preparations 2-4, 6-8. Most of the compounds investigated improved blood indices and prevented the development of polyarthritis.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arthritis, Experimental/prevention & control , Serine/analogs & derivatives , Animals , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Arthritis, Experimental/immunology , Arthritis, Experimental/pathology , Lethal Dose 50 , Male , Mice , Organ Size/drug effects , Rats , Rats, Wistar , Serine/chemistry , T-Lymphocytes/immunologyABSTRACT
Novel N- and O-acyl derivatives of threo-DL-phenylserine containing lipophilic long chain carboxylic or aryl(sulfon)amide groups were synthesized. Anti-inflammatory activity in carrageenin-induced paw edema model in rats was studied. Compound 10 had the most expressed anti-inflammatory effect over 24 h.