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01.01.2013 | Original Article

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

verfasst von: Bodil Bjørndal, Tore Grimstad, Daniel Cacabelos, Kim Nylund, Ole Gunnar Aasprong, Roald Omdal, Manuel Portero-Otin, Reinald Pamplona, Gülen Arslan Lied, Trygve Hausken, Rolf K. Berge

Erschienen in: Digestive Diseases and Sciences | Ausgabe 1/2013

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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.

Lomer MC. Dietary and nutritional considerations for inflammatory bowel disease. Proc Nutr Soc. 2011;70:329–335.PubMedCrossRef

Nicholls RJ. Review article: ulcerative colitis-surgical indications and treatment. Aliment Pharmacol Ther. 2002;16:25–28.PubMedCrossRef

Rosenstiel P, Schreiber S. Expression signatures, barriers and beyond: the role of oxidative stress in murine colitis and human inflammatory bowel disease revisited. Eur J Gastroenterol Hepatol. 2008;20:496–499.PubMedCrossRef

Dubuquoy L, Rousseaux C, Thuru X, Peyrin-Biroulet L, et al. PPARgamma as a new therapeutic target in inflammatory bowel diseases. Gut. 2006;55:1341–1349.PubMedCrossRef

Su CG, Wen X, Bailey ST, Jiang W, et al. A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J Clin Invest. 1999;104:383–389.PubMedCrossRef

Shah YM, Morimura K, Gonzalez FJ. Expression of peroxisome proliferator-activated receptor-gamma in macrophage suppresses experimentally induced colitis. Am J Physiol Gastrointest Liver Physiol. 2007;292:G657–G666.PubMedCrossRef

Celinski K, Dworzanski T, Korolczuk A, Piasecki R, et al. Effects of peroxisome proliferator-activated receptors-gamma ligands on dextran sodium sulphate-induced colitis in rats. J Physiol Pharmacol. 2011;62:347–356.PubMed

Pedersen G, Brynskov J. Topical rosiglitazone treatment improves ulcerative colitis by restoring peroxisome proliferator-activated receptor-gamma activity. Am J Gastroenterol. 2010;105:1595–1603.PubMedCrossRef

Bassaganya-Riera J, DiGuardo M, Climent M, Vives C, et al. Activation of PPARgamma and delta by dietary punicic acid ameliorates intestinal inflammation in mice. Br J Nutr. 2011;106:878–886.PubMedCrossRef

10.

Azuma YT, Nishiyama K, Matsuo Y, Kuwamura M, et al. PPARalpha contributes to colonic protection in mice with DSS-induced colitis. Int Immunopharmacol. 2010;10:1261–1267.PubMedCrossRef

11.

Peyrin-Biroulet L, Beisner J, Wang G, Nuding S, et al. Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon. Proc Natl Acad Sci USA. 2010;107:8772–8777.PubMedCrossRef

12.

Madsen L, Guerre-Millo M, Flindt EN, Berge K, et al. Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance. J Lipid Res. 2002;43:742–750.PubMed

13.

Berge RK, Madsen L, Vaagenes H, Tronstad KJ, Gottlicher M, Rustan AC. In contrast with docosahexaenoic acid, eicosapentaenoic acid and hypolipidaemic derivatives decrease hepatic synthesis and secretion of triacylglycerol by decreased diacylglycerol acyltransferase activity and stimulation of fatty acid oxidation. Biochem J. 1999;343:191–197.PubMedCrossRef

14.

Berge RK, Skorve J, Tronstad KJ, Berge K, Gudbrandsen OA, Grav H. Metabolic effects of thia fatty acids. Curr Opin Lipidol. 2002;13:295–304.PubMedCrossRef

15.

Dyroy E, Yndestad A, Ueland T, Halvorsen B, et al. Antiinflammatory effects of tetradecylthioacetic acid involve both peroxisome proliferator-activated receptor alpha-dependent and -independent pathways. Arterioscler Thromb Vasc Biol. 2005;25:1364–1369.PubMedCrossRef

16.

Aukrust P, Wergedahl H, Muller F, Ueland T, et al. Immunomodulating effects of 3-thia fatty acids in activated peripheral blood mononuclear cells. Eur J Clin Invest. 2003;33:426–433.PubMedCrossRef

17.

Muna ZA, Gudbrandsen OA, Wergedahl H, Bohov P, Skorve J, Berge RK. Inhibition of rat lipoprotein oxidation after tetradecylthioacetic acid feeding. Biochem Pharmacol. 2002;63:1127–1135.PubMedCrossRef

18.

Vigerust NF, Cacabelos D, Burri L, Berge K, et al. Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks. J Nutr Biochem. 2011. (Epub ahead of print). doi:10.1016/j.bbr.2011.03.031.

19.

Grimstad T, Bjorndal B, Cacabelos D, Aasprong OG, et al. Dietary supplementation of krill oil attenuates inflammation and oxidative stress in experimental ulcerative colitis in rats. Scand J Gastroenterol. 2011;47:49–58.PubMedCrossRef

20.

Spydevold O, Bremer J. Induction of peroxisomal beta-oxidation in 7800 C1 Morris hepatoma cells in steady state by fatty acids and fatty acid analogues. Biochim Biophys Acta. 1989;1003:72–79.PubMedCrossRef

21.

Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98:694–702.PubMed

22.

Carrier J, Aghdassi E, Platt I, Cullen J, Allard JP. Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced colitis. Aliment Pharmacol Ther. 2001;15:1989–1999.PubMedCrossRef

23.

Fu MX, Requena JR, Jenkins AJ, Lyons TJ, Baynes JW, Thorpe SR. The advanced glycation end product, Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. J Biol Chem. 1996;271:9982–9986.PubMedCrossRef

24.

Requena JR, Fu MX, Ahmed MU, Jenkins AJ, et al. Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein. Biochem J. 1997;322:317–325.PubMed

25.

Requena JR, Chao CC, Levine RL, Stadtman ER. Glutamic and aminoadipic semialdehydes are the main carbonyl products of metal-catalyzed oxidation of proteins. Proc Natl Acad Sci USA. 2001;98:69–74.PubMedCrossRef

26.

Petersson J, Schreiber O, Hansson GC, Gendler SJ, et al. Importance and regulation of the colonic mucus barrier in a mouse model of colitis. Am J Physiol Gastrointest Liver Physiol. 2011;300:G327–G333.PubMedCrossRef

27.

Natividad JM, Petit V, Huang X, de Palma G, et al. Commensal and probiotic bacteria influence intestinal barrier function and susceptibility to colitis in Nod1(−/−);Nod2(−/−) mice. Inflamm Bowel Dis. 2011. (Epub ahead of print). doi:10.1002/ibd.22848.PubMed

28.

Yamamoto-Furusho JK, Penaloza-Coronel A, Sanchez-Munoz F, Barreto-Zuniga R, Dominguez-Lopez A. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression is downregulated in patients with active ulcerative colitis. Inflamm Bowel Dis. 2011;17:680–681.PubMedCrossRef

29.

Raspe E, Madsen L, Lefebvre AM, Leitersdorf I, et al. Modulation of rat liver apolipoprotein gene expression and serum lipid levels by tetradecylthioacetic acid (TTA) via PPARalpha activation. J Lipid Res. 1999;40:2099–2110.PubMed

30.

Westergaard M, Henningsen J, Svendsen ML, Johansen C, et al. Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid. J Invest Dermatol. 2001;116:702–712.PubMedCrossRef

31.

Berge K, Tronstad KJ, Flindt EN, Rasmussen TH, et al. Tetradecylthioacetic acid inhibits growth of rat glioma cells ex vivo and in vivo via PPAR-dependent and PPAR-independent pathways. Carcinogenesis. 2001;22:1747–1755.PubMedCrossRef

32.

Strobel D, Goertz RS, Bernatik T. Diagnostics in inflammatory bowel disease: ultrasound. World J Gastroenterol. 2011;17:3192–3197.PubMed

33.

Dietrich CF. Significance of abdominal ultrasound in inflammatory bowel disease. Dig Dis. 2009;27:482–493.PubMedCrossRef

34.

Nylund K, Hausken T, Gilja OH. Ultrasound and inflammatory bowel disease. Ultrasound Q. 2010;26:3–15.PubMedCrossRef

35.

Delerive P, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors in inflammation control. J Endocrinol. 2001;169:453–459.PubMedCrossRef

36.

Marion-Letellier R, Dechelotte P, Iacucci M, Ghosh S. Dietary modulation of peroxisome proliferator-activated receptor gamma. Gut. 2009;58:586–593.PubMedCrossRef

37.

Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature. 1998;391:82–86.PubMedCrossRef

38.

Singh UP, Singh NP, Singh B, Hofseth LJ, et al. Resveratrol (trans-3,5,4′-trihydroxystilbene) induces silent mating type information regulation-1 and down-regulates nuclear transcription factor-kappaB activation to abrogate dextran sulfate sodium-induced colitis. J Pharmacol Exp Ther. 2010;332:829–839.PubMedCrossRef

39.

Verdin E, Hirschey MD, Finley LW, Haigis MC. Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling. Trends Biochem Sci. 2010;35:669–675.PubMedCrossRef

40.

Harel E, Rubinstein A, Nissan A, Khazanov E, et al. Enhanced transferrin receptor expression by proinflammatory cytokines in enterocytes as a means for local delivery of drugs to inflamed gut mucosa. PLoS One. 2011;6:e24202.PubMedCrossRef

41.

Koch TR, Yuan LX, Stryker SJ, Ratliff P, Telford GL, Opara EC. Total antioxidant capacity of colon in patients with chronic ulcerative colitis. Dig Dis Sci. 2000;45:1814–1819.PubMedCrossRef

42.

Pamplona R. Membrane phospholipids, lipoxidative damage and molecular integrity: a causal role in aging and longevity. Biochim Biophys Acta. 2008;1777:1249–1262.PubMedCrossRef

43.

Aoi Y, Terashima S, Ogura M, Nishio H, Kato S, Takeuchi K. Roles of nitric oxide (NO) and NO synthases in healing of dextran sulfate sodium-induced rat colitis. J Physiol Pharmacol. 2008;59:315–336.PubMed

Titel: Tetradecylthioacetic Acid Attenuates Inflammation and Has Antioxidative Potential During Experimental Colitis in Rats
verfasst von: Bodil Bjørndal
Tore Grimstad
Daniel Cacabelos
Kim Nylund
Ole Gunnar Aasprong
Roald Omdal
Manuel Portero-Otin
Reinald Pamplona
Gülen Arslan Lied
Trygve Hausken
Rolf K. Berge
Publikationsdatum: 01.01.2013
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 1/2013
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-012-2321-2

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