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Digestive Diseases and Sciences

, Volume 52, Issue 9, pp 2122–2132 | Cite as

Erdosteine Prevents Colonic Inflammation Through Its Antioxidant and Free Radical Scavenging Activities

  • Göksel Şener
  • Halil Aksoy
  • Özer Şehirli
  • Meral Yüksel
  • Cenk Aral
  • Nursal Gedik
  • Şule Çetinel
  • Berrak Ç. Yeğen
Original Paper

Abstract

After intracolonic administration of trinitrobenzene sulphonic acid (TNBS), Sprague-Dawley rats were treated orally either with saline or erdosteine (100 mg/kg per day), a sulfhydryl-containing antioxidant, for 3 days. On the 4th day, rats were decapitated and distal colon was removed for the macroscopic and microscopic damage scoring, for the measurement of malondialdehyde (MDA), glutathione (GSH) and collagen levels, myeloperoxidase (MPO) activity, luminol and lucigenin chemiluminescences (CL) and DNA fragmentation. Lactate dehydrogenase (LDH) activity, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and antioxidant capacity were assayed in blood samples. Colitis caused significant increases in the colonic CL values, macroscopic and microscopic damage scores, MDA and collagen levels, MPO activity and DNA fragmentation, along with a significant decrease in tissue GSH level. Similarly, serum cytokines and LDH were elevated in the saline-treated colitis group as compared with the control group. On the other hand, erdosteine treatment reversed all these biochemical indices, and histopathologic alterations induced by TNBS, suggesting that erdosteine protects the colonic tissue via its radical scavenging and antioxidant activities.

Keywords

Erdosteine Colitis Oxidative damage Inflammation TNBS 

References

  1. 1.
    Shanahan F (1993) Pathogenesis of ulcerative colitis. Lancet 342:407–411PubMedCrossRefGoogle Scholar
  2. 2.
    Yoshida N, Yoshikawa T, Yamaguchi T, Naito Y, Tanigawa T, Murase H, Kondo M (1999) A novel water-soluble vitamin E derivative protects against experimental colitis in rats. Antioxid Redox Signal 1:555–562PubMedGoogle Scholar
  3. 3.
    Gulluoglu BM, Kurtel H, Gulluoglu MG, Yegen C, Aktan AO, Dizdaroglu F, Yalin R, Yegen BC (1999) Role of endothelins in trinitrobenzene sulfonic acid-induced colitis in rats. Digestion 60:484–492PubMedCrossRefGoogle Scholar
  4. 4.
    Ukil A, Maity S, Karmakar S, Datta N, Vedasiromoni JR, Das PK (2003) Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis. Br J Pharmacol 139:209–218PubMedCrossRefGoogle Scholar
  5. 5.
    Babbs CF (1992) Oxygen radicals in ulcerative colitis. Free Radic Biol Med 13:169–181PubMedCrossRefGoogle Scholar
  6. 6.
    Imlay JA, Linn S (1988) DNA damage and oxygen radical toxicity. Science 240:1302–1309PubMedCrossRefGoogle Scholar
  7. 7.
    Sismonds NJ, Rampton DS (1994) Inflammatory bowel disease: a radical view. Gut 34:861–865Google Scholar
  8. 8.
    Shiratova A, Aoki S, Takada H, Kiriyama H, Ohto K, Hai K, Teraoka H, Matano S, Matsumoto K, Kamii K (1989) Oxygen derived free radicals generating capacity of polymorphonuclear cells in patients with ulcerative colitis. Digestion 44:163– 171Google Scholar
  9. 9.
    Suematsu M, Suzuki M, Kitahora T, Miura S, Suzuki K, Hibi T, Watanabe T, Nagata H, Asakura H, Tsuchiya M (1987) Increased respiratory burst of leukocytes in inflammatory bowel disease: The analysis of free radical generation by using chemiluminescence probe. J Clin Lab Immunol 24:125–128PubMedGoogle Scholar
  10. 10.
    Yoshikawa T, Yamaguchi T, Yoshida N, Yamamato H, Kitazumi S, Takahashi S, Naito Y, Kondo M (1997) Effect of Z-103 on TNB-induced colitis in rats. Digestion 58:464–468PubMedCrossRefGoogle Scholar
  11. 11.
    Ahnfelt-Ronne I, Nielsen OH, Christensen A, Langholz E, Binder V, Riis P (1990) Clinical evidence supporting the radical scavenger mechanism of 5-aminosalicylic acid. Gastroenterology 98:1162–1169PubMedGoogle Scholar
  12. 12.
    Dechant KL, Noble S (1996) Erdosteine. Drugs 52:875–881PubMedGoogle Scholar
  13. 13.
    Moretti M, Bottrighi P, Dallari R, Da Porto R, Dolcetti A, Grandi P, Garuti G, Guffanti E, Roversi P, De Gugliemo M, Potena A; EQUALIFE Study Group (2004) The effect of long-term treatment with erdosteine on chronic obstructive pulmonary disease: the EQUALIFE Study. Drugs Exp Clin Res 30:143– 152PubMedGoogle Scholar
  14. 14.
    Braga PC, Dal Sasso M, Zuccotti T (2000) Assessment of the antioxidant activity of the SH metabolite I of erdosteine on human neutrophil oxidative bursts. Arzneimittelforschung. 50:739– 746PubMedGoogle Scholar
  15. 15.
    Inglesi M, Nicola M, Fregnan GB, Bradamante S, Pagani G (1994) Synthesis and free radical scavenging properties of the enantiomers of erdosteine. Farmaco 40:703–708PubMedGoogle Scholar
  16. 16.
    Boyaci H, Maral H, Turan G, Basyigit I, Dillioglugil MO, Yildiz F, Tugay M, Pala A, Ercin C (2006) Effects of erdosteine on bleomycin-induced lung fibrosis in rats. Mol Cell Biochem 281:129–137PubMedCrossRefGoogle Scholar
  17. 17.
    Yagmurca M, Fadillioglu E, Erdogan H, Ucar M, Sogut S, Irmak MK (2003) Erdosteine prevents doxorubicin-induced cardiotoxicity in rats. Pharmacol Res 48:377–382PubMedCrossRefGoogle Scholar
  18. 18.
    Isik B, Bayrak R, Akcay A, Sogut S (2006) Erdosteine against acetaminophen induced renal toxicity. Mol Cell Biochem 287:185–191PubMedCrossRefGoogle Scholar
  19. 19.
    Demiralay R, Gursan N, Erdem H (2006) The effects of erdosteine, N-acetylcysteine, and vitamin E on nicotine-induced apoptosis of pulmonary cells. Toxicology 219:197–207PubMedCrossRefGoogle Scholar
  20. 20.
    Wallace JL, Braquet P, Ibbotson GC, MacNaugton WK, Cirino G (1989) Assessment of the role of platelet activating factor in an animal model of inflammatory bowel disease. J Lipid Med 1:13–23Google Scholar
  21. 21.
    Gué M, Bonbonne J, Fioramonti J, More C, Del Rio-Lacléze C, Comera C, Bueno L (1997) Stress-induced enhancement of colitis in rats: CRF and arginine vasopressin are not involved. Am J Physiol 272:G84–G91PubMedGoogle Scholar
  22. 22.
    Lopez De Leon A, Rojkind M (1985) A simple micromethod for collagen and total protein determination in formalin-fixed paraffin-embedded sections. J Histochem Cytochem 33:737– 743PubMedGoogle Scholar
  23. 23.
    Martinek RG (1972) A rapid ultraviolet spectrophotometric lactic dehydrogenase assay. Clin Chem Acta 40:91–99CrossRefGoogle Scholar
  24. 24.
    Bradley PP, Priebat DA, Christersen RD, Rothstein G (1982) Measurement of cutaneous inflammation. Estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209PubMedCrossRefGoogle Scholar
  25. 25.
    Davies GR, Simmonds NJ, Stevens TR, Sheaff MT, Banatvala N, Laurenson IF, Blake DR, Rampton DS (1994) Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo. Gut 35:179–185PubMedGoogle Scholar
  26. 26.
    Ohara Y, Peterson TE, Harrisorn DG (1993) Hypercholesterolemia increases endothelial superoxide anion production. J. Clin Invest 92:2546–2551Google Scholar
  27. 27.
    Haklar G, Ulukaya-Durakbaşa C, Yüksel M, Daglı T, Yalcin AS (1998) Oxygen radicals and nitric oxide in rat mesenteric ischemia-reperfusion: modulation by L-arginine and N-nitro-L-arginine methyl ester. Clin Exp Pharmacol Physiol 25:908– 912PubMedCrossRefGoogle Scholar
  28. 28.
    Beuge JA, Aust SD (1978) Microsomal lipid peroxidation. Meth Enzymol 52:302–311CrossRefGoogle Scholar
  29. 29.
    Beutler E (1975) Glutathione in red blood cell metabolism. In: A manual of biochemical methods. Grune & Stratton, New York; pp 112–114Google Scholar
  30. 30.
    Wyllie H (1980) Glucocorticoid induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556PubMedCrossRefGoogle Scholar
  31. 31.
    Burton K (1956) A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62:315–323PubMedGoogle Scholar
  32. 32.
    Grisham MB, Granger DN (1988) Neutrophil-mediated mucosal injury. Role of reactive oxygen metabolites. Dig Dis Sci 33(3 Suppl):6S–15SPubMedCrossRefGoogle Scholar
  33. 33.
    Elson CO, Sartor RB, Tennyson GS, Riddell RH (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367PubMedCrossRefGoogle Scholar
  34. 34.
    Guo X, Wang WP, Ko JK, Cho CH (1999) Involvement of neutrophils and free radicals in the potentiating effects of passive cigarette smoking on inflammatory bowel disease in rats. Gastroenterology 117:884–892PubMedCrossRefGoogle Scholar
  35. 35.
    Dal Sasso M, Culici M, Guffanti EE, Bianchi T, Fonti E, Braga PC (2005) A combination of budesonide and the SH-metabolite I of erdosteine acts synergistically in reducing chemiluminescence during human neutrophil respiratory burst. Pharmacology 74:127–134PubMedCrossRefGoogle Scholar
  36. 36.
    Grisham MB (1994) Oxidants and free radicals in inflammatory bowel disease. Lancet 24;344(8926):859–861CrossRefGoogle Scholar
  37. 37.
    Braga PC, Dal Sasso M, Culici M, Verducci P, Lo Verso R, Marabini L (2006) Effect of metabolite I of erdosteine on the release of human neutrophil elastase. Pharmacology 77:150–154PubMedCrossRefGoogle Scholar
  38. 38.
    Siddiqui A, Ancha H, Tedesco D, Lightfoot S, Stewart CA, Harty RF (2006) Antioxidant therapy with N-acetylcysteine plus mesalamine accelerates mucosal healing in a rodent model of colitis. Dig Dis Sci 51:698–705PubMedCrossRefGoogle Scholar
  39. 39.
    Stark G (2005) Functional consequences of oxidative membrane damage. J Membr Biol 205:1–16PubMedCrossRefGoogle Scholar
  40. 40.
    Isozaki Y, Yoshida N, Kuroda M, Takagi T, Handa O, Kokura S, Ichikawa H, Naito Y, Okanoue T, Yoshikawa T (2006) Effect of a novel water-soluble vitamin E derivative as a cure for TNBS-induced colitis in rats. Int J Mol Med 17:497–502PubMedGoogle Scholar
  41. 41.
    Colon AL, Madrigal JL, Menchen LA, Moro MA, Lizasoain I, Lorenzo P, Leza JC (2004) Stress increases susceptibility to oxidative/nitrosative mucosal damage in an experimental model of colitis in rats. Dig Dis Sci 49:1713–1721PubMedCrossRefGoogle Scholar
  42. 42.
    Jahovic N, Gedik N, Ercan F, Sirvanci S, Yuksel M, Sener G, Alican I (2006) Effects of statins on experimental colitis in normocholesterolemic rats. Scand J Gastroenterol 41:954–962PubMedCrossRefGoogle Scholar
  43. 43.
    Peifer C, Wagner G, Laufer S (2006) New approaches to the treatment of inflammatory disorders small molecule inhibitors of p38 MAP kinase. Curr Top Med Chem 6:113–149PubMedCrossRefGoogle Scholar
  44. 44.
    Cuzzocrea S, Mazzon E, Serraino I, Lepore V, Terranova ML, Ciccolo A, Caputi AP (2001) Melatonin reduces dinitrobenzene sulfonic acid-induced colitis. J Pineal Res 30:1– 12PubMedCrossRefGoogle Scholar
  45. 45.
    Hosoe H, Kaise T, Ohmori K (2002) Effects on the reactive oxygen species of erdosteine and its metabolite in vitro. Arzneimittelforschung 52:435–440PubMedGoogle Scholar
  46. 46.
    Dal Sasso M, Culici M, Bianchi T, Fonti E, Braga PC (2004) Inhibitory effects of metabolite I of erdosteine on the generation of nitric oxide and peroxynitrite chemiluminescence by human neutrophils. Pharmacology 71:120–127PubMedCrossRefGoogle Scholar
  47. 47.
    Jang YY, Song JH, Shin YK, Han ES, Lee CS (2003) Depressant effects of ambroxol and erdosteine on cytokine synthesis, granule enzyme release, and free radical production in rat alveolar macrophages activated by lipopolysaccharide. Pharmacol Toxicol 92:173–179PubMedCrossRefGoogle Scholar
  48. 48.
    Ross D (1988) Glutathione, free radicals and chemotherapeutic agents. Mechanisms of free-radical induced toxicity and glutathione-dependent protection. Pharmacol Ther 37:231–249PubMedCrossRefGoogle Scholar
  49. 49.
    Reiter RJ, Tan DX, Osuna C, Gitto E (2000) Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci 7:444–458PubMedCrossRefGoogle Scholar
  50. 50.
    D’Odorico A, Bortolan S, Cardin R, D’Inca’ R, Martines D, Ferronato A, Sturniolo GC (2001) Reduced plasma antioxidant concentrations and increased oxidative DNA damage in inflammatory bowel disease. Scand J Gastroenterol 36:1289–1294PubMedCrossRefGoogle Scholar
  51. 51.
    Martin AR, Villegas I, La Casa C, Alarcon de la Lastra C (2003) The cyclo-oxygenase-2 inhibitor, rofecoxib, attenuates mucosal damage due to colitis induced by trinitrobenzene sulphonic acid in rats. Eur J Pharmacol 481:281–291PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Göksel Şener
    • 1
  • Halil Aksoy
    • 2
  • Özer Şehirli
    • 1
  • Meral Yüksel
    • 3
  • Cenk Aral
    • 4
  • Nursal Gedik
    • 5
  • Şule Çetinel
    • 6
  • Berrak Ç. Yeğen
    • 7
  1. 1.Department of Pharmacology, School of PharmacyMarmara UniversityİstanbulTurkey
  2. 2.Department of Biochemistry, School of PharmacyMarmara UniversityIstanbulTurkey
  3. 3.Vocational School of Health Related ProfessionsMarmara UniversityIstanbulTurkey
  4. 4.Department of Medical Biology, School of MedicineMarmara UniversityIstanbulTurkey
  5. 5.Division of BiochemistryKasimpasa Military HospitalIstanbulTurkey
  6. 6.Department of Histology-Embryology, School of MedicineMarmara UniversityIstanbulTurkey
  7. 7.Department of Physiology, School of MedicineMarmara UniversityIstanbulTurkey

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