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

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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.

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References

  1. Shanahan F (1993) Pathogenesis of ulcerative colitis. Lancet 342:407–411

    Article  PubMed  CAS  Google Scholar 

  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 1:555–562

    PubMed  CAS  Google Scholar 

  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 60:484–492

    Article  PubMed  CAS  Google Scholar 

  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 139:209–218

    Article  PubMed  CAS  Google Scholar 

  5. Babbs CF (1992) Oxygen radicals in ulcerative colitis. Free Radic Biol Med 13:169–181

    Article  PubMed  CAS  Google Scholar 

  6. Imlay JA, Linn S (1988) DNA damage and oxygen radical toxicity. Science 240:1302–1309

    Article  PubMed  CAS  Google Scholar 

  7. Sismonds NJ, Rampton DS (1994) Inflammatory bowel disease: a radical view. Gut 34:861–865

    Google Scholar 

  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– 171

    Google Scholar 

  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 24:125–128

    PubMed  CAS  Google Scholar 

  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 58:464–468

    Article  PubMed  CAS  Google Scholar 

  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 98:1162–1169

    PubMed  CAS  Google Scholar 

  12. Dechant KL, Noble S (1996) Erdosteine. Drugs 52:875–881

    PubMed  CAS  Google Scholar 

  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– 152

    PubMed  CAS  Google Scholar 

  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– 746

    PubMed  CAS  Google Scholar 

  15. Inglesi M, Nicola M, Fregnan GB, Bradamante S, Pagani G (1994) Synthesis and free radical scavenging properties of the enantiomers of erdosteine. Farmaco 40:703–708

    PubMed  CAS  Google Scholar 

  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 281:129–137

    Article  PubMed  CAS  Google Scholar 

  17. Yagmurca M, Fadillioglu E, Erdogan H, Ucar M, Sogut S, Irmak MK (2003) Erdosteine prevents doxorubicin-induced cardiotoxicity in rats. Pharmacol Res 48:377–382

    Article  PubMed  CAS  Google Scholar 

  18. Isik B, Bayrak R, Akcay A, Sogut S (2006) Erdosteine against acetaminophen induced renal toxicity. Mol Cell Biochem 287:185–191

    Article  PubMed  CAS  Google Scholar 

  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 219:197–207

    Article  PubMed  CAS  Google Scholar 

  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 1:13–23

    CAS  Google Scholar 

  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–G91

    PubMed  Google Scholar 

  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– 743

    PubMed  CAS  Google Scholar 

  23. Martinek RG (1972) A rapid ultraviolet spectrophotometric lactic dehydrogenase assay. Clin Chem Acta 40:91–99

    Article  CAS  Google Scholar 

  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 78:206–209

    Article  PubMed  CAS  Google Scholar 

  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 35:179–185

    PubMed  CAS  Google Scholar 

  26. Ohara Y, Peterson TE, Harrisorn DG (1993) Hypercholesterolemia increases endothelial superoxide anion production. J. Clin Invest 92:2546–2551

    Google Scholar 

  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– 912

    Article  PubMed  CAS  Google Scholar 

  28. Beuge JA, Aust SD (1978) Microsomal lipid peroxidation. Meth Enzymol 52:302–311

    Article  Google Scholar 

  29. Beutler E (1975) Glutathione in red blood cell metabolism. In: A manual of biochemical methods. Grune & Stratton, New York; pp 112–114

    Google Scholar 

  30. Wyllie H (1980) Glucocorticoid induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556

    Article  PubMed  CAS  Google Scholar 

  31. Burton K (1956) A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62:315–323

    PubMed  CAS  Google Scholar 

  32. Grisham MB, Granger DN (1988) Neutrophil-mediated mucosal injury. Role of reactive oxygen metabolites. Dig Dis Sci 33(3 Suppl):6S–15S

    Article  PubMed  CAS  Google Scholar 

  33. Elson CO, Sartor RB, Tennyson GS, Riddell RH (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367

    Article  PubMed  CAS  Google Scholar 

  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 117:884–892

    Article  PubMed  CAS  Google Scholar 

  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 74:127–134

    Article  PubMed  CAS  Google Scholar 

  36. Grisham MB (1994) Oxidants and free radicals in inflammatory bowel disease. Lancet 24;344(8926):859–861

    Article  Google Scholar 

  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 77:150–154

    Article  PubMed  CAS  Google Scholar 

  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 51:698–705

    Article  PubMed  CAS  Google Scholar 

  39. Stark G (2005) Functional consequences of oxidative membrane damage. J Membr Biol 205:1–16

    Article  PubMed  CAS  Google Scholar 

  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 17:497–502

    PubMed  CAS  Google Scholar 

  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 49:1713–1721

    Article  PubMed  CAS  Google Scholar 

  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 41:954–962

    Article  PubMed  CAS  Google Scholar 

  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 6:113–149

    Article  PubMed  CAS  Google Scholar 

  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– 12

    Article  PubMed  CAS  Google Scholar 

  45. Hosoe H, Kaise T, Ohmori K (2002) Effects on the reactive oxygen species of erdosteine and its metabolite in vitro. Arzneimittelforschung 52:435–440

    PubMed  CAS  Google Scholar 

  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 71:120–127

    Article  PubMed  CAS  Google Scholar 

  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 92:173–179

    Article  PubMed  CAS  Google Scholar 

  48. Ross D (1988) Glutathione, free radicals and chemotherapeutic agents. Mechanisms of free-radical induced toxicity and glutathione-dependent protection. Pharmacol Ther 37:231–249

    Article  PubMed  CAS  Google Scholar 

  49. Reiter RJ, Tan DX, Osuna C, Gitto E (2000) Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci 7:444–458

    Article  PubMed  CAS  Google Scholar 

  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 36:1289–1294

    Article  PubMed  CAS  Google Scholar 

  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 481:281–291

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Göksel Şener.

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Şener, G., Aksoy, H., Şehirli, Ö. et al. Erdosteine Prevents Colonic Inflammation Through Its Antioxidant and Free Radical Scavenging Activities. Dig Dis Sci 52, 2122–2132 (2007). https://doi.org/10.1007/s10620-007-9801-9

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  • DOI: https://doi.org/10.1007/s10620-007-9801-9

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