Investigation of the Role of the TRPA1 Ion Channel in Conveying the Effect of Dimethyl Trisulfide on Vascular and Histological Changes in Serum-Transfer Arthritis.

Autor: Bátai IZ; Department of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Szigeti u. 12, H-7624 Pecs, Hungary.; Molecular Pharmacology Research Group, Szentagothai Research Centre, University of Pecs, Ifjusag utja 20, H-7624 Pecs, Hungary.; Department of Anaesthesiology and Intensive Therapy, Clinical Centre, University of Pecs, Ifjusag utja 13, H-7624 Pecs, Hungary., Dombi Á; Department of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Szigeti u. 12, H-7624 Pecs, Hungary.; Molecular Pharmacology Research Group, Szentagothai Research Centre, University of Pecs, Ifjusag utja 20, H-7624 Pecs, Hungary., Borbély É; Department of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Szigeti u. 12, H-7624 Pecs, Hungary.; Molecular Pharmacology Research Group, Szentagothai Research Centre, University of Pecs, Ifjusag utja 20, H-7624 Pecs, Hungary., Fehér Á; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1, H-4032 Debrecen, Hungary., Papp F; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1, H-4032 Debrecen, Hungary., Varga Z; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1, H-4032 Debrecen, Hungary., Mócsai A; Department of Physiology, Faculty of Medicine, Semmelweis University, Tuzolto u. 37-47, H-1094 Budapest, Hungary., Helyes Z; Department of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Szigeti u. 12, H-7624 Pecs, Hungary.; Molecular Pharmacology Research Group, Szentagothai Research Centre, University of Pecs, Ifjusag utja 20, H-7624 Pecs, Hungary., Pintér E; Department of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Szigeti u. 12, H-7624 Pecs, Hungary.; Molecular Pharmacology Research Group, Szentagothai Research Centre, University of Pecs, Ifjusag utja 20, H-7624 Pecs, Hungary., Pozsgai G; Department of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Szigeti u. 12, H-7624 Pecs, Hungary.; Molecular Pharmacology Research Group, Szentagothai Research Centre, University of Pecs, Ifjusag utja 20, H-7624 Pecs, Hungary.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2022 May 27; Vol. 15 (6). Date of Electronic Publication: 2022 May 27.
DOI: 10.3390/ph15060671
Abstrakt: Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases. Its therapy is often challenging, even in the era of biologicals. Previously, we observed the anti-inflammatory effects of garlic-derived organic polysulfide dimethyl trisulfide (DMTS). Some of these effects were mediated by activation of the TRPA1 ion channel. TRPA1 was mostly expressed in a subset of nociceptor neurons. We decided to investigate the action of DMTS in K/BxN serum-transfer arthritis, which is a relevant model of RA. TRPA1 gene knockout (KO) and wild-type (WT) mice were used. The interaction of DMTS and TRPA1 was examined using a patch clamp in CHO cells. Arthritis was characterized by mechanical hyperalgesia, paw swelling, movement range of the ankle joint, hanging performance, plasma extravasation rate, myeloperoxidase activity, and histological changes in the tibiotarsal joint. DMTS activated TRPA1 channels dose-dependently. DMTS treatment reduced paw swelling and plasma extravasation in both TRPA1 WT and KO animals. DMTS-treated TRPA1 KO animals developed milder collagen deposition in the inflamed joints than WT ones. TRPA1 WT mice did not exhibit significant cartilage damage compared to ones administered a vehicle. We concluded that DMTS and related substances might evolve into novel complementary therapeutic aids for RA patients.
Databáze: MEDLINE
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