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In Vivo Evaluation of Two 5‐Aminosalicylic Acid Derivatives Considered as Potential Therapeutic Agents
Author(s) -
Gutierrez Sanchez M,
Rosales Hernandez M,
Padilla Martinez I,
Correa Basurto J,
Mendieta Wejebe J
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.621.1
Subject(s) - myeloperoxidase , in vivo , chemistry , aminosalicylic acid , pharmacology , hydrogen peroxide , in vitro , antioxidant , acute toxicity , catalysis , biochemistry , toxicity , inflammation , medicine , immunology , organic chemistry , biology , microbiology and biotechnology
Several studies have shown that myeloperoxidase (MPO) is intimately involved in the initiation and progression of many inflammatory diseases [Lee et al., 2013]. Based on the foregoing, our research group has shown recently that two new derivatives of the 5‐aminosalicylic acid (5‐ASA), the 5‐{[(2 E )‐3‐bromo‐3‐carboxyprop‐2‐enoyl]amino}‐2‐hydroxybenzoic acid ( 1 ) and 5‐[(4‐carboxybutanoyl)amino]‐2‐hydroxybenzoic acid ( 2 ), inhibit the catalytic activity of MPO and have antioxidant capacity in vitro . Therefore, this study aimed to evaluate the inhibitory effect of these compounds on catalytic activity of MPO in vivo . Compounds 1 and 2 were synthesized and characterized chemically. The acute toxicity was determined in two rodent species [Guía 425, OECD, 2008]. The edema induction model was performed in the mouse ear by using 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) [Salazar et al., 2011]. The MPO activity was determined using the oxidation method of O‐dianisidine in presence of hydrogen peroxide [Quaiyoom et al., 2012]. Both compounds were obtained with acceptable yields (70%). These showed be safe for their use in rat and mouse (DL50˃1098 mg/kg). Furthermore their administration in ears of TPA‐treated mice, led to a significant decrease of catalytic activity of MPO in comparison with the positive control (indomethacin). Therefore, these results suggest continue with the preclinical study of both compounds, since these could be used in future as potential therapeutic agents for the treatment of inflammatory diseases.