Varga 2017 Inflammopharmacology

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Varga G, Ugocsai M, Hartmann P, Lajkó N, Molnár R, Szűcs S, Jász DK, Érces D, Ghyczy M, Tóth G, Boros M (2017) Acetylsalicylic acid-tris-hydroxymethyl-aminomethane reduces colon mucosal damage without causing gastric side effects in a rat model of colitis. Inflammopharmacology 26:261-71.

» PMID: 28451776

Varga G, Ugocsai M, Hartmann P, Lajko N, Molnar R, Szucs S, Jasz DK, Erces D, Ghyczy M, Toth G, Boros M (2017) Inflammopharmacology

Abstract: 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.

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.

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.

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.

Keywords: Acetylsalicylic-acid; Gastritis; Mitochondria; Non-steroidal anti-inflammatory drugs; TNBS colitis Bioblast editor: Kandolf G O2k-Network Lab: HU Szeged Boros M

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Infectious, Other 

Organism: Rat  Tissue;cell: Liver  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k