Reduced mucosal side-effects of acetylsalicylic acid after conjugation with tris-hydroxymethyl-aminomethane. Synthesis and biological evaluation of a new anti-inflammatory compound
Acetylsalicylic acid (ASA) causes adverse haemorrhagic reactions in the upper gastrointestinal (GI) tract, and previous results have suggested that combination therapy with 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) could provide protection in this scenario. Based on this hypothesis, our aim...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2016
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| Sorozat: | EUROPEAN JOURNAL OF PHARMACOLOGY
781 |
| doi: | 10.1016/j.ejphar.2016.04.019 |
| mtmt: | 3060190 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/9454 |
| LEADER | 02903nab a2200289 i 4500 | ||
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| 001 | publ9454 | ||
| 005 | 20191204144158.0 | ||
| 008 | 160712s2016 hu o 0|| zxx d | ||
| 022 | |a 0014-2999 | ||
| 024 | 7 | |a 10.1016/j.ejphar.2016.04.019 |2 doi | |
| 024 | 7 | |a 3060190 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a zxx | ||
| 100 | 1 | |a Varga Gabriella | |
| 245 | 1 | 0 | |a Reduced mucosal side-effects of acetylsalicylic acid after conjugation with tris-hydroxymethyl-aminomethane. Synthesis and biological evaluation of a new anti-inflammatory compound |h [elektronikus dokumentum] / |c Varga Gabriella |
| 260 | |c 2016 | ||
| 300 | |a 181-189 | ||
| 490 | 0 | |a EUROPEAN JOURNAL OF PHARMACOLOGY |v 781 | |
| 520 | 3 | |a Acetylsalicylic acid (ASA) causes adverse haemorrhagic reactions in the upper gastrointestinal (GI) tract, and previous results have suggested that combination therapy with 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) could provide protection in this scenario. Based on this hypothesis, our aim was to develop a new compd. from ASA and Tris precursors and to characterize the biol. effects of ASA-Tris and the derivs. ASA-bis- and mono-hydroxymethyl-aminomethane (ASA-Bis, ASA-Mono, resp.) using in vivo and in vitro test systems. ASA or ASA conjugates (0.55 mmol/kg, each) were administered intragastrically to Sprague-Dawley rats. Changes in the mucosal structure and in the serosal microcirculation were detected by in vivo imaging techniques, the plasma TNF-alpha, tissue xanthine oxidoreductase and myeloperoxidase activities, and liver cytochrome c changes were also detd. In two sep. series, platelet aggregation and carrageenan arthritis-induced inflammatory pain were measured in control, ASA and ASA-Tris-treated groups. Severe mucosal injury and a significant decrease in serosal red blood cell velocity developed in the ASA-treated group and an ∼2-fold elevation in proinflammatory mediator levels evolved. ASA-Tris did not cause bleeding, microcirculatory dysfunction, mucosal injury or an elevation in proinflammatory markers. The ASA-Mono and ASA-Bis conjugates did not cause macroscopic bleeding, but the inflammatory activation was apparent. ASA-Tris did not influence the cyclooxygenase-induced platelet aggregation significantly, but the inflammatory pain was reduced as effectively as in the case of equimolar ASA doses. ASA-Tris conjugation is an effective approach through which the GI side-effects of ASA are controlled by decreasing the cytokine-mediated progression of pro-inflammatory events. [on SciFinder(R)] | |
| 700 | 0 | 1 | |a Lajkó Norbert |e aut |
| 700 | 0 | 1 | |a Ugocsai Melinda |e aut |
| 700 | 0 | 1 | |a Érces Dániel |e aut |
| 700 | 0 | 1 | |a Horváth Gyöngyi |e aut |
| 700 | 0 | 1 | |a Tóth Gábor |e aut |
| 700 | 0 | 1 | |a Boros Mihály |e aut |
| 700 | 0 | 1 | |a Ghyczy Miklós |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/9454/1/Varga_EJP_2016_u.pdf |z Dokumentum-elérés |