Conjugation with Tris Decreases the Risk of Ketoprofen-Induced Mucosal Damage and Reduces Inflammation-Associated Methane Production in a Rat Model of Colitis
Melinda Ugocsai,
Anett Bársony,
Réka Anna Varga,
Ámos Gajda,
Noémi Vida,
Norbert Lajkó,
Benedek Rónaszéki,
Gábor Tóth,
Mihály Boros,
Dániel Érces,
Gabriella Varga
Affiliations
Melinda Ugocsai
Department of Orthopaedics, Albert Szent-Györgyi Medical School, University of Szeged, H-6725 Szeged, Hungary
Anett Bársony
Department of Surgery, Albert Szent-Györgyi Medical School, University of Szeged, H-6725 Szeged, Hungary
Réka Anna Varga
Institute of Surgical Research, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
Ámos Gajda
Institute of Surgical Research, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
Noémi Vida
Institute of Surgical Research, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
Norbert Lajkó
Institute of Surgical Research, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
Benedek Rónaszéki
Second Department of Internal Medicine and Cardiology Center, Albert Szent-Györgyi Medical School, University of Szeged, H-6725 Szeged, Hungary
Gábor Tóth
Department of Medical Chemistry, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
Mihály Boros
Institute of Surgical Research, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
Dániel Érces
Institute of Surgical Research, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
Gabriella Varga
Institute of Surgical Research, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
We have designed a new compound from the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (Ket) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors, with the aim to reduce the gastrointestinal (GI) side effects of NSAID therapies. We investigated mucosal reactions in a standard rat model of colitis together with methane generation as a possible indicator of pro-inflammatory activation under this condition (approval number: V./148/2013). Whole-body methane production (photoacoustic spectroscopy) and serosal microcirculation (intravital videomicroscopy) were measured, and mucosal damage was assessed (conventional histology; in vivo laser-scanning endomicroscopy). Inflammatory markers were measured from tissue and blood samples. Colitis induced an inflammatory response, morphological colonic damage and increased methane output. Ket treatment lowered inflammatory activation and colonic mucosal injury, but macroscopic gastric bleeding and increased methane output were present. Ket-Tris reduced inflammatory activation, methane emission and colonic mucosal damage, without inducing gastric injury. Conjugation with Tris reduces the GI side effects of Ket and still decreases the inflammatory response in experimental colitis. Methane output correlates with the mucosal inflammatory response and non-invasively demonstrates the effects of anti-inflammatory treatments.
