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Tetradecylthioacetic Acid Attenuates Inflammation and Has Antioxidative Potential During Experimental Colitis in Rats

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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.

Aims

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.

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Acknowledgments

The authors would like to thank Eline Milde, Marie Sannes Ramsvik, Kari Williams and Randi Sandvik for excellent technical assistance. Ingeborg Kvivik, Kari Espedal and Marita Hanasand are thanked for their help during the cytokine analyses. This study was supported by Nordforsk (grant no. 070010, MitoHealth), and the Research Council of Norway (grant no. 190287/110) to RKB, and the Board of Nutrition Programmes (University of Bergen and Western Norway Regional Health Authority) to TH. DC holds a fellowship from the Spanish Ministry of Health (FI0800707). Work carried out at the Department of Experimental Medicine was supported by grants from the Spanish Ministry of Science and Innovation (BFU2009-11879/BFI), the Autonomous Government of Catalonia (2009SGR735), and the Spanish Ministry of Health (PI081843) to MPO and RP. The study was also supported by the COST B-35 action.

Conflict of interest

The authors have no conflict of interest, financial or otherwise, with respect to this work.

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Authors and Affiliations

  1. Institute of Medicine, University of Bergen, PO box 7800, 5020, Bergen, Norway

    Bodil Bjørndal, Tore Grimstad, Kim Nylund, Roald Omdal, Trygve Hausken & Rolf K. Berge

  2. Department of Medicine, Stavanger University Hospital, 4068, Stavanger, Norway

    Tore Grimstad & Roald Omdal

  3. Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida, 25198, Lleida, Spain

    Daniel Cacabelos, Manuel Portero-Otin & Reinald Pamplona

  4. National Centre of Ultrasound in Gastroenterology, Haukeland University Hospital, 5021, Bergen, Norway

    Kim Nylund

  5. Department of Pathology, Stavanger University Hospital, 4068, Stavanger, Norway

    Ole Gunnar Aasprong

  6. Division of Gastroenterology, Haukeland University Hospital, 5021, Bergen, Norway

    Gülen Arslan Lied & Trygve Hausken

  7. Department of Heart Disease, Haukeland University Hospital, 5021, Bergen, Norway

    Rolf K. Berge

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  1. Bodil Bjørndal
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Correspondence to Bodil Bjørndal.

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Bjørndal, B., Grimstad, T., Cacabelos, D. et al. Tetradecylthioacetic Acid Attenuates Inflammation and Has Antioxidative Potential During Experimental Colitis in Rats. Dig Dis Sci 58, 97–106 (2013). https://doi.org/10.1007/s10620-012-2321-2

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