title: Long-Term Effects of (-)-Epigallocatechin Gallate (EGCG) on Pristane-Induced Arthritis (PIA) in Female Dark Agouti Rats.
abstract: Rheumatoid arthritis (RA)--a widespread chronic inflammatory disease in industrialized countries--is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the pharmacological mode of action of this polyphenol.
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology (IZI) Leipzig, Perlickstraße 1, 04103 Leipzig, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Leichsenring
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology (IZI) Leipzig, Perlickstraße 1, 04103 Leipzig, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bäcker
authors.affiliation: Department of Chemistry, Division of Biochemistry, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Furtmüller
authors.affiliation: Department of Chemistry, Division of Biochemistry, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Obinger
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology (IZI) Leipzig, Perlickstraße 1, 04103 Leipzig, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Lange
authors.affiliation: Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstraße 16-18, 04107 Leipzig, Germany.|Translational Centre for Regenerative Medicine (TRM) Leipzig, Philipp-Rosenthal-Str. 55, 04103 Leipzig, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Flemmig
mesh_terms: D000818:Animals; D005260:Female; D051381:Rats; D001168:Arthritis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D002908:Chronic Disease; D007249:Inflammation / Q000097:blood / Q000473:pathology; D008727:Methotrexate / Q000627:therapeutic use; D009961:Orosomucoid / Q000378:metabolism; D009195:Peroxidase / Q000097:blood; D013729:Terpenes
chemical_list: D015415:Biomarkers; D002392:Catechin; C045651:epigallocatechin gallate; D008727:Methotrexate; D009961:Orosomucoid; D009195:Peroxidase; C009042:pristane; D013729:Terpenes