Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Varga 2017 Inflammopharmacology

From Bioblast
Publications in the MiPMap
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