title: Tetradecylthioacetic acid attenuates inflammation and has antioxidative potential during experimental colitis in rats.
abstract: BACKGROUND
  The fatty acid analogue tetradecylthioacetic acid (TTA) is a moderate pan-activator of peroxisome proliferator-activated receptors (PPARs), and has in previous studies showed potential as an antioxidant and anti-inflammatory agent, both through PPAR and non-PPAR mediated mechanisms.
  
  
  OBJECTIVE
  This study aimed to determine whether TTA could alleviate dextran sulfate sodium (DSS)-induced colitis in rats.
  
  
  METHODS
  Male Wistar rats were fed a control diet (control- and DSS-group) or a diet supplemented with 0.4 % TTA (TTA + DSS-group) for 30 days, and DSS was added to the drinking water the last 7 days. Ultrasound measurements were performed at day 29. At day 30, rats were sacrificed and the distal colon was removed for histological evaluation and measurement of cytokine levels, oxidative damage, and gene expression.
  
  
  RESULTS
  The disease activity index was not improved in the TTA + DSS-group compared to the DSS-group. However, ultrasound measurements showed a significantly reduced colonic wall thickening in the TTA + DSS-group. TNF-α, IL-1β, and IL-6 were reduced at the protein and mRNA level in the TTA + DSS-group. Moreover, TTA-treated rats demonstrated reduced colonic oxidative damage, while inducible nitric oxide synthase 2 mRNA expression was elevated in both the DSS- and TTA + DSS-groups. PPARγ signaling may be involved in the anti-inflammatory response to TTA, as Pparg mRNA expression was significantly upregulated in colon.
  
  
  CONCLUSIONS
  This study demonstrated that the pan-PPAR agonist TTA reduced colonic oxidative damage and cytokine levels in a rat model of colitis, and its potential to ameliorate colitis should be further explored.
authors.affiliation: Institute of Medicine, University of Bergen, P.O. box 7800, 5020, Bergen, Norway. bodil.bjorndal@med.uib.no
authors.forename: Bodil
authors.initials: B
authors.lastname: Bjørndal
authors.forename: Tore
authors.initials: T
authors.lastname: Grimstad
authors.forename: Daniel
authors.initials: D
authors.lastname: Cacabelos
authors.forename: Kim
authors.initials: K
authors.lastname: Nylund
authors.forename: Ole Gunnar
authors.initials: OG
authors.lastname: Aasprong
authors.forename: Roald
authors.initials: R
authors.lastname: Omdal
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero-Otin
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
authors.forename: Gülen Arslan
authors.initials: GA
authors.lastname: Lied
authors.forename: Trygve
authors.initials: T
authors.lastname: Hausken
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity*; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D013440:Sulfides; C062078:1-(carboxymethylthio)tetradecane; D016264:Dextran Sulfate