nach oben

Digestive Diseases and Sciences

Erschienen in:

01.08.2009 | Original Article

Effect of N-acetylcysteine on the Murine Model of Colitis Induced by Dextran Sodium Sulfate Through Up-Regulating PON1 Activity

verfasst von: Yu You, Jian-Jiang Fu, Jun Meng, Guo-Dong Huang, Yu-Hui Liu

Erschienen in: Digestive Diseases and Sciences | Ausgabe 8/2009

Einloggen, um Zugang zu erhalten

Abstract

Reactive oxygen species (ROS) are increased in inflammatory bowel disease (IBD) and have been implicated as mediators of intestinal inflammation. We investigated the hypothesis that N-acetylcysteine (NAC) as a glutathione (GSH) precursor attenuates disease progression in a murine dextran sodium sulfate (DSS)-induced colitis model. A colitis model was induced by adding 5% DSS into the drinking water for 7 days. BALB/c mice were injiciatur enema with saline, 5-ASA, N-acetylcysteine, respectively, and free drinking water as control group. DSS-treated mice developed severe colitis as shown by bloody diarrhea, weight loss, and pathologic involvement. Colon lengths were significantly decreased in DSS-treated mice with decreased GSH activity too (P < 0.01). ROS in the colon, the level of interleukin 1β (IL-1β) in colonic mucosa, serum tumor necrosis factor a (TNF-α), MPO, and MDA were significantly increased in DSS-treated animals (P < 0.01), with decreased PON1 activity (P < 0.01). However, NAC significantly decreased colonic MPO activity, ROS, TNF-α and IL-1β levels and increased PON1 activity and GSH concentration. Moreover, NAC attenuated the macroscopic colonic damage and the histopathologic changes-induced by DSS while similar to 5-ASA group. These results suggest that NAC may be effective in the treatment of colitis through its up-regulating PON1 and scavenging oxygen-derived free radicals.

Strober W, Murray PJ, Kitani A, et al. Signalling pathways and molecular interactions of NOD1 and NOD2. Nat Rev Immunol. 2006;6:9–20. doi:10.1038/nri1747.PubMedCrossRef

Netea MG, Kullberg BJ, de Jong DJ, et al. NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn’s disease. Eur J Immunol. 2004;34:2052–2059. doi:10.1002/eji.200425229.PubMedCrossRef

Mawdsley JE, Jenkins DG, Macey MG, et al. The effect of hypnosis on systemic and rectal mucosal measures of inflammation in ulcerative colitis. Am J Gastroenterol. 2008;103(6):1460–1469. doi:10.1111/j.1572-0241.2008.01845.x.PubMedCrossRef

Lee HS, Han SY, Bae EA, et al. Lactic acid bacteria inhibit proinflammatory cytokine expression and bacterial glycosaminoglycan degradation activity in dextran sulfate sodium-induced colitic mice. Int Immunopharmacol. 2008;8(4):574–580. doi:10.1016/j.intimp.2008.01.009.PubMedCrossRef

Rahimi R, Nikfar S, Abdollahi M. Meta-analysis technique confirms the effectiveness of anti-TNF-alpha in the management of active ulcerative colitis when administered in combination with corticosteroids. Med Sci Monit. 2007;13(7):PI13–PI18.PubMed

Rahimi R, Nikfar S, Abdollahi Mohammad. Do anti-tumor necrosis factors induce response and remission in patients with acute refractory Crohn’s disease? A systematic meta-analysis of controlled clinical trials. Biomed Pharmacother. 2007;61(1):75–80. doi:10.1016/j.biopha.2006.06.022.PubMedCrossRef

Rahimi R, Nikfar S, Rezaie A, et al. A meta-analysis of broad spectrum antibiotic therapy in patients with active Crohn’s disease. Clin Ther. 2006;28:1983–1988. doi:10.1016/j.clinthera.2006.12.012.PubMedCrossRef

Rahimi R, Nikfar S, Rezaie A, et al. A meta-analysis of antibiotic therapy for active ulcerative colitis. Dig Dis Sci. 2007;52(11):2920–2925. doi:10.1007/s10620-007-9760-1.PubMedCrossRef

Helieh Oza TS, Theresa Chenb S, Craig McClain J, et al. Antioxidants as novel therapy in a murine model of colitis. J Nutr Biochem. 2005;16:297–304. doi:10.1016/j.jnutbio.2004.09.007.CrossRef

10.

Isozaki Y, Yoshida N, Kuroda M, et al. Effect of a novel water-soluble vitamin E derivative as a cure for TNBS-induced colitis in rats. Int J Mol Med. 2006;17(3):497–502.PubMed

11.

Kruidenier L, Kuiper I, Lamers CB, et al. Intestinal oxidative damage in inflammatory bowel disease: semi-quantification, localization, and association with mucosal antioxidants. J Pathol. 2003;201(1):28–36. doi:10.1002/path.1409.PubMedCrossRef

12.

Mrtensson J, Jain A, Meister A. Glutathione is required for intestinal function. Proc Natl Acad Sci USA. 1990;87:1715–1719. doi:10.1073/pnas.87.5.1715.CrossRef

13.

Soltan-Sharifi MS, Mojtahedzadeh M, Najafi A, et al. Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione, and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms. Hum Exp Toxicol. 2007;26(9):697–703. doi:10.1177/0960327107083452.PubMedCrossRef

14.

Ebrahimi F, Esmaily H, Baeeri M, et al. Molecular evidences on the benefit of N-acetylcysteine in experimental colitis. Cent Eur J Biol 2008;3(2):135–142. doi:10.2478/s11535-008-0005-x.CrossRef

15.

Durrington PN, Mackness B, Mackness MI. Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol. 2001;21:473–480.PubMed

16.

Baskol G, Baskol M, Yurci A, et al. Serum paraoxonase 1 activity and malondialdehyde levels in patients with ulcerative colitis. Cell Biochem Funct. 2006;24(3):283–286. doi:10.1002/cbf.1224.PubMedCrossRef

17.

Rothem L, Hartman C, Dahan A, et al. Paraoxonases are associated with intestinal inflammatory diseases and intracellularly localized to the endoplasmic reticulum. Free Radic Biol Med. 2007;43:730–739. doi:10.1016/j.freeradbiomed.2007.05.003.PubMedCrossRef

18.

Kanauchi O, Nakamura T, Agata K, et al. Effects of germinated barley food stuff on dextran sulfate sodium-induced colitis in rats. J Gastroenterol. 1998;33:179–188. doi:10.1007/s005350050067.PubMedCrossRef

19.

Sanders LM, Henderson CE, Hong MY, et al. Pro-oxidant environment of the colon compared to the small intestine may contribute to greater cancer susceptibility. Cancer Lett. 2004;208:155–161. doi:10.1016/j.canlet.2003.12.007.PubMedCrossRef

20.

Suzuki K, Sugimura K, Hasegawa K, et al. Activated platelets in ulcerative colitis enhance the production of reactive oxygen species by polymorphonuclear leukocytes. Scand J Gastroenterol. 2001;36:1301–1306. doi:10.1080/003655201317097164.PubMedCrossRef

21.

Qualls JE, Kaplan AM, van Rooijen N, et al. Suppression of experimental colitis by intestinal mononuclear phagocytes. J Leukoc Biol. 2006;80(4):802–815. doi:10.1189/jlb.1205734.PubMedCrossRef

22.

Rezaie A, Parker RD, Abdollahi M. Oxidative stress and pathogenesis of inflammatory bowel disease: an epiphenomenon or the cause? Dig Dis Sci. 2007;52(9):2015–2021. doi:10.1007/s10620-006-9622-2.PubMedCrossRef

23.

Banan A, Choudhary S, Zhang Y, et al. Oxidant-induced intestinal barrier disruption and its prevention by growth factors in a human colonic cell line: role of the microtubule cytoskeleton. Free Radic Biol Med. 2000;28(5):727–738. doi:10.1016/S0891-5849(00)00160-X.PubMedCrossRef

24.

Kruidenier L, Kuiper I, Van Duijn W, et al. Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease. J Pathol. 2003;201(1):17–27. doi:10.1002/path.1408.PubMedCrossRef

25.

Aw TY. Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility. Toxicol Appl Pharmacol. 2005;204(3):320–328. doi:10.1016/j.taap.2004.11.016.PubMedCrossRef

26.

Aviram M, Billecke S, Sorenson R, et al. Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different than that required for its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R. Arterioscler Thromb Vasc Biol. 1998;18:1617–1624.PubMed

27.

Aviram M, Rosenblat M, Billecke S, et al. Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med. 1999;26:892–904.PubMedCrossRef

28.

Liu Y-H, Liu L-Y, Wu J-X, et al. Comparison of Captopril and Enalapril to study the role of the sulfhydryl-group in improvement of endothelial dysfunction with ACE inhibitors in high dieted methionine mice. J Cardiovasc Pharmacol. 2006;47(1):82–88.PubMedCrossRef

29.

Nosal’ova V, Cerna S, Bauer V. Effect of N-acetylcysteine on colitis induced by acetic acid in rats. Gen.Pharmaco. 2000;35(2):77–81.

30.

Scarpulla RC. Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta. 2002;1576:1–14.PubMed

31.

Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066–1071.PubMedCrossRef

32.

Kumon Y, Nakauchi Y, Suehiro T, et al. Proinflammatory cytokines but not acute phase serum amyloid A or C-reactive protein, downregulate paraoxonase 1 (PON1) expression by Hep G2. Amyloid. 2002;9:160–164.PubMed

33.

Chromik AM, Müller AM, Albrecht M, et al. Oral administration of taurolidine ameliorates chronic DSS colitis in mice. J Invest Surg. 2007;20(5):273–282.PubMedCrossRef

34.

Paganelli M, Albanese C, Borrelli O, et al. Inflammation is the main determinant of low bone mineral density in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2007;13(4):416–423.PubMedCrossRef

Titel: Effect of N-acetylcysteine on the Murine Model of Colitis Induced by Dextran Sodium Sulfate Through Up-Regulating PON1 Activity
verfasst von: Yu You
Jian-Jiang Fu
Jun Meng
Guo-Dong Huang
Yu-Hui Liu
Publikationsdatum: 01.08.2009
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 8/2009
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-008-0563-9

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Effect of N-acetylcysteine on the Murine Model of Colitis Induced by Dextran Sodium Sulfate Through Up-Regulating PON1 Activity

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Ist Fasten vor Koronarinterventionen wirklich nötig?

Typ-2-Diabetes: Ernährungsunsicherheit vervierfacht Risiko für schwere Hypoglykämien

Mehr Brustkrebs, aber weniger andere gynäkologische Tumoren mit Levonorgestrel-IUS

GLP-1-Agonist Semaglutid wirkt kardio- und nephroprotektiv

Update Innere Medizin

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2009

Hospitalizations for Inflammatory Bowel Disease Among US Military Veterans 1975–2006

Long-Term Efficacy of Lansoprazole in Preventing Relapse of Erosive Reflux Esophagitis

How Should We Train Capsule Endoscopy? A Pilot Study of Performance Changes During a Structured Capsule Endoscopy Training Program

Effect of Dietary Turmeric on Breath Hydrogen

The Evaluation of Premenopausal Women with Anemia: What Is the Yield of Gastrointestinal Endoscopy?

Behavioral Treatment of Habitual Rumination: Case Reports

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Ist Fasten vor Koronarinterventionen wirklich nötig?

Typ-2-Diabetes: Ernährungsunsicherheit vervierfacht Risiko für schwere Hypoglykämien

Mehr Brustkrebs, aber weniger andere gynäkologische Tumoren mit Levonorgestrel-IUS

GLP-1-Agonist Semaglutid wirkt kardio- und nephroprotektiv

Update Innere Medizin