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Alterations in Antioxidant Power and Levels of Epidermal Growth Factor and Nitric Oxide in Saliva of Patients with Inflammatory Bowel Diseases

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Abstract

Despite extensive investigation, the pathophysiology of human inflammatory bowel disease (IBD) remains incompletely understood. We examined the existence of oxidative and nitrosative stress and also alterations in epidermal growth factor (EGF) secretion in saliva of IBD patients. Saliva samples were obtained from 30 nonsmoking IBD patients including 16 Crohn’s disease (CD) patients and 16 ulcerative colitis (UC) patients and 16 age- and sex-matched controls. Samples were analyzed for thiobarbituric reactive substances (TBARS) as a marker of lipid peroxidation, ferric reducing ability (antioxidant power), and EGF and nitric oxide (NO) levels. Saliva TBARS levels increased significantly (P &< 0.01) in CD patients but not in UC patients. Analysis of antioxidant power revealed that saliva of CD patients has lower antioxidant power (P &< 0.01) than saliva of the healthy control population. The concentration of EGF was found to be increased (P &< 0.01) in saliva of CD patients in comparison to that of healthy subjects. NO levels increased in saliva of both CD and UC patients in comparison to that of healthy subjects. It is concluded that excessive NO production is present in saliva of both CD and UC patients but only saliva of CD patients is oxidatively stressed. EGF secretion is normal in UC patients, although CD patients show a significant increase in salivary EGF levels.

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References

  1. Cross RK, Wilson KT: Nitric oxide in inflammatory bowel disease. Inflamm Bowel Dis 9(3):179–189, 2003

    PubMed  Google Scholar 

  2. Singer II, Kawka DW, Scott S, Weidner JR, Mumford RA, Riehl TE, Stenson WF: Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease. Gastroenterology 111:871–885, 1996

    CAS  PubMed  Google Scholar 

  3. Kimura H, Hokari R, Miura S, Shigematsu T, Hirokawa M, Akiba Y, Kurose I, Higuchi H, Fujimori H, Tsuzuki Y, Serizawa H, Ishii H: Increased expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in colonic mucosa of patients with active ulcerative colitis. Gut 42:180–187, 1998

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Playford RJ: Peptides and gastrointestinal mucosal integrity. Gut 37:595–597, 1995

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Sinha A, Nightingale J, West KP, Berlanga-Acosta J, Playford RJ: Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis. N Engl J Med 349(4):350–357, 2003

    CAS  PubMed  Google Scholar 

  6. Miettinen PJ, Berger JE, Meneses J, Phung Y, Pedersen RA, Werb Z, Derynck R: Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 376:337–341, 1995

    CAS  PubMed  Google Scholar 

  7. Boughton-Smith NK, Evans SM, Hawkey CJ, Cole AT, Balsitis M, Whittle BJ, Moncada S: Nitric oxide synthase activity in ulcerative colitis and Crohn’s disease. Lancet 342:338–340, 1993

    CAS  PubMed  Google Scholar 

  8. Rachmilewitz D, Stamler JS, Bachwich D, Karmeli F, Ackerman Z, Podolsky DK: Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn’s disease. Gut 36:718–723, 1995

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Leonard N, Bishop AE, Polak JM, Talbot IC: Expression of nitric oxide synthase in inflammatory bowel disease is not affected by corticosteroid treatment. J Clin Pathol 51:750–753, 1998

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Guihot G, Guimbaud R, Bertrand V, Narcy-Lambare B, Couturier D, Duee PH, Chaussade S, Blachier F: Inducible nitric oxide synthase activity in colon biopsies from inflammatory areas: Correlation with inflammation intensity in patients with ulcerative colitis but not with Crohn’s disease. Amino Acids 18:229–237, 2000

    CAS  PubMed  Google Scholar 

  11. Kimura H, Miura S, Shigematsu T, Ohkubo N, Tsuzuki Y, Kurose I, Higuchi H, Akiba Y, Hokari R, Hirokawa M, Serizawa H, Ishii H: Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn’s disease. Dig Dis Sci 42:1047–1054, 1997

    CAS  PubMed  Google Scholar 

  12. Middleton SJ, Shorthouse M, Hunter JO: Increased nitric oxide synthesis in ulcerative colitis. Lancet 341:465–646, 1993

    CAS  PubMed  Google Scholar 

  13. Vento P, Kiviluoto T, Jarvinen HJ, Karkkainen P, Kivilaakso E, Soinila S: Expression of inducible and endothelial nitric oxide synthases in pouchitis. Inflamm Bowel Dis 7:120–127, 2001

    CAS  PubMed  Google Scholar 

  14. Lundberg JO, Hellstrom PM, Lundberg JM, Alving K: Greatly increased luminal nitric oxide in ulcerative colitis. Lancet 344:1673–1674, 1994

    CAS  PubMed  Google Scholar 

  15. Ljung T, Herulf M, Beijer E, Jacobsson H, Lundberg J, Finkel Y, Hellstrom PM: Rectal nitric oxide assessment in children with Crohn disease and ulcerative colitis: Indicator of ileocaecal and colorectal affection. Scand J Gastroenterol 36:1073–1076, 2001

    CAS  PubMed  Google Scholar 

  16. Ljung T, Beijer E, Herulf M, Weitzberg E, Lundberg JO, Finkel Y, Hellstrom PM: Increased rectal nitric oxide in children with active inflammatory bowel disease. J Pediatr Gastroenterol Nutr 34:302–306, 2002

    CAS  PubMed  Google Scholar 

  17. Perner A, Nordgaard I, Matzen P, Rask-Madsen J: Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis and uninflamed bowel. Scand J Gastroenterol 37:183–818, 2002

    CAS  PubMed  Google Scholar 

  18. Iwashita E: Greatly increased mucosal nitric oxide in ulcerative colitis determined in situ by a novel nitric oxide-selective microelectrode. J Gastroenterol Hepatol 13:391–539, 1998

    CAS  PubMed  Google Scholar 

  19. Goggins MG, Shah SA, Goh J, Cherukuri A, Weir DG, Kelleher D, Mahmud N: Increased urinary nitrite, a marker of nitric oxide, in active inflammatory bowel disease. Mediat Inflamm 10:69–73, 2001

    CAS  Google Scholar 

  20. Rees DC, Satsangi J, Cornelissen PL, Travis SP, White J, Jewell DP: Are serum concentrations of nitric oxide metabolites useful for predicting the clinical outcome of severe ulcerative colitis? Eur J Gastroenterol Hepatol 7:227–230, 1995

    CAS  PubMed  Google Scholar 

  21. Dijkstra G, Zandvoort AJ, Kobold AC, de Jager-Krikken A, Heeringa P, van Goor H, van Dullemen HM, Tervaert JW, van de Loosdrecht A, Moshage H, Jansen PL: Increased expression of inducible nitric oxide synthase in circulating monocytes from patients with active inflammatory bowel disease. Scand J Gastroenterol 37:546–554, 2002

    CAS  PubMed  Google Scholar 

  22. Koek GH, Verleden GM, Evenepoel P, Rutgeerts P: Activity related increase of exhaled nitric oxide in Crohn’s disease and ulcerative colitis: A manifestation of systemic involvement? Respir Med 96:530–535, 2002

    CAS  PubMed  Google Scholar 

  23. Wendland BE, Aghdassi E, Tam C, Carrier J, Steinhart AH, Wolman SL, Baron D, Allard JP: Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease. Am J Clin Nutr 74(2):259–264, 2001

    CAS  PubMed  Google Scholar 

  24. D’Odorico A. Bortolan S, Cardin R: Reduced plasma antioxidantconcentrations and increased oxidative DNA damage in inflammatory Bowel Disease. Scand J Gastroenterol 36:1289–1294, 2001

    PubMed  Google Scholar 

  25. Miralles-Barrachina O, Savoye G, Belmonte-Zalar L, Hochain P, Ducrotte P, Hecketsweiler B, Lerebours E, Dechelotte P: Low levels of glutathione in endoscopic biopsies of patients with Crohn’s colitis: The role of malnutrition. Clin Nutr 18:313–317, 1999

    CAS  PubMed  Google Scholar 

  26. Ardite E, Sans M, Panes J, Romero FJ, Pique JM, Fernandez-Checa JC: Replenishment of glutathione levels improves mucosal function in experimental acute colitis. Lab Invest 8:735–744, 2000

    Google Scholar 

  27. Sido B, Hack V, Hochlehnert A, Lipps H, Herfarth C, Droge W: Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Gut 42:485–492, 1998

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Holmes EW, Young SL, Eiznhamer D, Keshavarzian A: Glutathione content of colonic mucosa: Evidence for oxidative damage in active ulcerative colitis. Dig Dis Sci 43:1088–1095, 1998

    CAS  PubMed  Google Scholar 

  29. Sturniolo GC, Mestriner C, Lecis PE, D’Odorico A, Venturi C, Irato P, Cecchetto A, Tropea A, Longo G, D’Inca R: Altered plasma and mucosal concentrations of trace elements and antioxidants in active ulcerative colitis. Scand J Gastroenterol 33:644–649, 1998

    CAS  PubMed  Google Scholar 

  30. Geerling BJ, Badart-Smook A, van Deursen C, van Houwelingen AC, Russel MG, Stockbrugger RW, Brummer RJ: Nutritional supplementation with N-3 fatty acids and antioxidants in patients with Crohn’s disease in remission: Effects on antioxidant status and fatty acid profile. Inflamm Bowel Dis 6:77–84, 2000

    CAS  PubMed  Google Scholar 

  31. Buffington GD, Doe WF: Altered ascorbic acid status in the mucosa from inflammatory bowel disease patients. Free Radic Res 22:131–143, 1995

    Google Scholar 

  32. D’Odorico A, Pozzato F, Minotto M, et al.: Plasma carotenoids and other antioxidant levels in Crohn’s disease. Gastroenterology 110:A897, 1996

    Google Scholar 

  33. Geerling BJ, Badart-Smook A, Stockbrugger RW, Brummer RJ: Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission. Am J Clin Nutr 67:919–926, 1998

    CAS  PubMed  Google Scholar 

  34. Sedghi S, Keshavarzian A, Klamut M, Einznhamer D, Zarling EJ: Elevated breath ethane levels in active ulcerative colitis: evidence for excessive lipid peroxidation. Am J Gastroenterol 89:2217–2221, 1994

    CAS  PubMed  Google Scholar 

  35. Pelli MA, Trovalerelli G, Capodicasa E, De Medio GE, Bassotti G: Breath alkanes determination in ulcerative colitis and Crohn’s disease. Dis Colon Rectum 42:71–76, 1999

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  37. Grisham MB: Oxidants and free radicals in inflammatory bowel disease. Lancet 344:859–861, 1994

    CAS  PubMed  Google Scholar 

  38. Green AR: Peptide regulatory factors: Multifunctional mediators of cellular growth and differentiation. Lancet 1:705–707, 1989

    CAS  PubMed  Google Scholar 

  39. Sporn MB, Roberts AB: Autocrine secretion—10 years later. Ann Intern Med 117:408–414, 1992

    CAS  PubMed  Google Scholar 

  40. Nathan C, Sporn M. Cytokines in context: J Cell Biol 113:981–986, 1991

    CAS  PubMed  Google Scholar 

  41. Sporn MB, Roberts AB: Transforming growth factor-[beta]: Recent progress and new challenges. J Cell Biol 119:1017–1021, 1992

    CAS  PubMed  Google Scholar 

  42. Dignass AU, Sturm A: Peptide growth factors in the intestine. Eur J Gastroenterol Hepatol 13(7):763–770, 2001

    CAS  PubMed  Google Scholar 

  43. Wong WM, Wright NA: Epidermal growth factor, epidermal growth factor receptors, intestinal growth, and adaptation. J Parenter Enteral Nutr 23:S83–S88, 1999

    CAS  Google Scholar 

  44. Challacombe DN, Wheeler EE: Trophic action of epidermal growth factor on human duodenal mucosa cultured in vitro. Gut 32:991–993, 1991

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Reeves JR, Richards RC, Cooke T: The effects of intracolonic EGF on mucosal growth and experimental carcinogenesis. Br J Cancer 63:223–226, 1991

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Kurokowa M, Lynch K, Podolsky DK: Effects of growth factors on an intestinal epithelial cell line: Transforming growth factor beta inhibits proliferation and stimulates differentation. Biochem Biophys Res Commun 142:775–782, 1987

    CAS  PubMed  Google Scholar 

  47. Carpenter G, Cohen S. Epidermal growth factor: J Biol Chem 265:7709–7712, 1990

    CAS  PubMed  Google Scholar 

  48. Fitzpatrick LR, Wang P, Johnson LR: Effect of epidermal growth on polyamine-synthesizing enzymes in rat enterocytes. Am J Physiol 252:G209–G214, 1987

    CAS  PubMed  Google Scholar 

  49. Opleta-Madsen K, Hardin J, Gall DG: Epidermal growth factor upregulates intestinal electrolyte and nutrient transport. Am J Physiol 260:G807–G814, 1991

    CAS  PubMed  Google Scholar 

  50. Riegler M, Sedivy R, Sogukoglu T, et al.: Epidermal growth factor promotes rapid response to epithelial injury in rabbit duodenum in vitro. Gastroenterology 111:28–36, 1996

    CAS  PubMed  Google Scholar 

  51. Dignass AU, Podolsky DK: Cytokine modulation of intestinal epithelial cell restitution: Central role of transforming growth factor beta. Gastroenterology 105:1323–1332, 1993

    CAS  PubMed  Google Scholar 

  52. Sullivan PB, Brueton MJ, Tabara ZB, Goodlad RA, Lee CY, Wright NA: Epidermal growth factor in necrotising enteritis. Lancet 338:53–54, 1991

    CAS  PubMed  Google Scholar 

  53. Chowdhury A, Fukuda R, Fukumoto S: Growth factor mRNA expression in normal colorectal mucosa and in uninvolved mucosa from ulcerative colitis patients. J Gastroenterol 31:353–360, 1996

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Golshid Jahanshahi, Vian Motavasel, Ali Rezaie & Mohammad Abdollahi

  2. Department of Gastrointestinal Disease, Tehran University of Medical Sciences, Tehran, Iran

    Ali A. Hashtroudi & Naser E. Daryani

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  1. Golshid Jahanshahi
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  2. Vian Motavasel
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  3. Ali Rezaie
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  4. Ali A. Hashtroudi
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  5. Naser E. Daryani
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  6. Mohammad Abdollahi
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Correspondence to Mohammad Abdollahi.

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Jahanshahi, G., Motavasel, V., Rezaie, A. et al. Alterations in Antioxidant Power and Levels of Epidermal Growth Factor and Nitric Oxide in Saliva of Patients with Inflammatory Bowel Diseases. Dig Dis Sci 49, 1752–1757 (2004). https://doi.org/10.1007/s10620-004-9564-5

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