Acetylsalicylic acid-tris-hydroxymethyl-aminomethane reduces colon mucosal damage without causing gastric side effects in a rat model of colitis
- 27.04.2017
- Original Article
Erschienen in:
- Verfasst von
- Gabriella Varga
- Melinda Ugocsai
- Petra Hartmann
- Norbert Lajkó
- Réka Molnár
- Szilárd Szűcs
- Dávid Kurszán Jász
- Dániel Érces
- Miklós Ghyczy
- Gábor Tóth
- Mihály Boros
- Erschienen in
- Inflammopharmacology | Ausgabe 1/2018
Abstract
Background
We have developed a novel compound from acetylsalicylic acid (ASA) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors with ASA-like anti-inflammatory efficacy and reduced the mucosa-damaging side-effects. Our aim was to examine local and remote consequences of ASA-Tris administration in 2-,4-,6-trinitrobenzene-sulfonic acid (TNBS)-induced colitis as compared to ASA or mesalamine (5-aminosalicylate) treatment.
Methods
Sprague–Dawley rats were randomized to five groups (n = 6, each), and TNBS enemas were performed. Group 1 was the negative control; group 2 was the untreated colitis group. 12 hour after colitis induction repeated doses of ASA, ASA-Tris (both 0.55 mmol/kg) and mesalamine (0.77 mmol/kg) were given 3 times daily for 3 days to groups 3–5. On day 3 of colitis, the in vivo histology of the colon and stomach was investigated. Tissue xanthine-oxidoreductase, myeloperoxidase, nitrite/nitrate changes, and circulating TNF-alpha levels were measured. In addition, liver mitochondria were examined with high-resolution respirometry to analyze alterations in the electron transport chain.
Results
TNBS enema significantly elevated inflammatory enzyme activities, NO production, TNF-alpha concentration, and induced morphological damage in the colon. ASA-treatment reduced the inflammatory marker levels and mucosal injury in the colon, but gastric tissue damage was present. ASA-Tris- and mesalamine-treatments significantly reduced the cytokine levels, inflammatory enzyme activities, and colonic mucosal damage without inducing gastric injury. Also, ASA significantly reduced the Complex IV-linked respiration of liver mitochondria, which was not observed after ASA-Tris-treatment.
Conclusion
As compared to ASA, ASA-Tris conjugation provides significant protection against the colonic injury and cytokine-mediated progression of inflammatory events in experimental colitis without influencing the gastric epithelial structure.
Anzeige
- Titel
- Acetylsalicylic acid-tris-hydroxymethyl-aminomethane reduces colon mucosal damage without causing gastric side effects in a rat model of colitis
- Verfasst von
-
Gabriella Varga
Melinda Ugocsai
Petra Hartmann
Norbert Lajkó
Réka Molnár
Szilárd Szűcs
Dávid Kurszán Jász
Dániel Érces
Miklós Ghyczy
Gábor Tóth
Mihály Boros
- Publikationsdatum
- 27.04.2017
- Verlag
- Springer International Publishing
- Erschienen in
-
Inflammopharmacology / Ausgabe 1/2018
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608 - DOI
- https://doi.org/10.1007/s10787-017-0354-z
Dieser Inhalt ist nur sichtbar, wenn du eingeloggt bist und die entsprechende Berechtigung hast.