Abstract
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation whose cellular components are capable of oxidative respiratory bursts that may result in tissue injury. Mucosal biopsies were analyzed for protein carbonyl content (POPs), DNA oxidation products [8-hydroxy-2′-deoxyguanosine (8-OHdG)], reactive oxygen intermediates (ROIs), trace metals (copper, zinc, and iron) and superoxide dismutase (Cu-Zn SOD). In Crohn's disease biopsies, there was an increase in ROIs, POPs, 8-OHdG, and iron, while decreased copper and Cu-Zn SOD activity were found in inflamed tissues compared to controls. For ulcerative colitis, there was an increase in ROIs, POPs, and iron in inflamed tissue compared to controls, while decreased zinc and copper were observed. An imbalance in the formation of reactive oxygen species and antioxidant micronutrients may be important in the pathogenesis and/or perpetuation of the tissue injury in IBD and may provide a rationale for therapeutic modulation with antioxidants.
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References
Halliwell B: Drug antixoidant effects—a basis for drug selection? Drugs 42(4):569–605, 1991
Turrens JF, Boveris A: Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. J Biochem 191:421–427, 1980
Weiss SJ: Tissue destruction by neutrophils. N Engl J Med 320:365–376, 1989
Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, et al: Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 328(20):1450–1456, 1993
Suryaprabha P, Das UN, Ramesh G, Kumar KV, Kumar GS: Reactive oxygen species, lipid peroxides, and essential fatty acids in patients with rheumatoid arthritis and systemic lupus erythematosis. Prostaglandins Leukot Essent Fatty Acids 43(4):251–255, 1991
Yoshikawa T: Free radicals and their scavengers in Parkinson's disease. Eur Neurol 33(suppl 1):60–68, 1993
Kilgare KS, Lucchesi BR: Reperfusion injury after myocardial infarction: The role of free radicals and the inflammatory response. Clin Biochem 26(5):359–370, 1993
Gutteridge JM: Ageing and free radicals. Med Lab Sci 49(4):313–318, 1992
Cross CE, Halliwell B, Borish ET, Pryor WA, Ames BN, Saul RL, McCord JM, Harman D: Oxygen derived radicals and reperfusion injury—Davis conference, oxygen radicals and human disease. Ann Intern Med 107(4):526–545, 1987
Otamiri T, Sjodahl R: Oxygen radicals: Their role in selected gastrointestinal disorders. Dig Dis 9(3):133–141, 1991
Babbs CF: Oxygen radicals in ulcerative colitis. Free Radic Biol Med 13:169–181, 1992
Emerit J, Pelletier S, Tosoni-Verlignue D, Mollet M: Phase II trial of copper zinc superoxide dismutase in the treatment of Crohn's disease. Free Radic Biol Med 7(2):145–149, 1989
Wright JP, Mee S, Parfitt A, Marks IN, et al: Vitamin A therapy in patients with Crohn's disease. Gastroenterology 88(2):512–514, 1985
Ahnfelt-Ronne I, Nielson OH: The antiinflammatory moiety of sulfasalazine, 5-ASA, is a radical scavenger. Agents Actions 21(1–2):191–194, 1987
Ahnfelt-Ronne I, Haagen Nielsen O, Christensen A, Langholz E, Binder V, Riis P: Clinical evidence supporting the radical scavenger mechanism of 5-aminosalicylic acid. Gastroenterology 98:1162–1169, 1990
Harvey RF, Bradshaw JM: A simple index of Crohn's disease activity. Lancet 1:514, 1980
Truelove SC, Witts LJ: Cortisone in ulcerative colitis. Final report on a therapeutic trial. Br Med J 2:1041, 1955
Kirshner JB, Shorter RG: Recent developments in “nonspecific” inflammatory bowel disease. N Engl J Med 306:775–785, 837–848, 1982
Lowry OH, Rosebrough NJ, Farr AL, Randal RJ. Anal Biochem 100:201, 1979
Carney JM, Starke-Reed PE, Oliver CN, Landum RW, et al: Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compoundN-tert-butyl—phenylnitrone. Proc Natl Acad Sci USA 88:3633–3636, 1991
Oliver CN, Starke-Reed PE, Stadtman ER, Lui GJ, et al: Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion induced injury to gerbil brain. Proc Natl Acad Sci USA 87:5144–5147, 1990
Simmonds NJ, Allen RE, Stevens TRJ: Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel disease. Gastroenterology 103(1):186–196, 1992
Keshavarzian A, Sedghi S, Kanofsky J, List T, Robinson C, Ibrahim C, Winship D: Excessive production of reactive oxygen metabolites by inflamed colon: analysis by chemiluminescence probe. Gastroenterology 103:177–185, 1992
Kirby KS: New methods for isolation of deoxyribonucleic acids: Evidence on the nature of bonds between deoxyribonucleic acid and protein. Biochem J 66:495–504, 1957
Floyd RA, West MS, Eneff JE, Wong PK, Tingley DT, Hogsett WE: Conditions influencing yeild and analysis of 8-hydroxy-2'-deoxyguanosine in oxidatively damaged DNA. Anal Biochem 188:155–158, 1990
Winyard PG, Perrett D, Blake DR, Harris G, Chipman JK: Measurement of DNA oxidation products. Anal Proc 27:224–227, 1990
Shanahan F, Targan SR: Mechanisms of tissue injury in inflammatory bowel disease.In Current Topics in Gastroenterology—Inflammatory Bowel Disease. RP McDermott, WF Stenson (eds). New York, Elsevier Science Publishing, 1992, pp 77–93
Mahida YR, Wu KC, Jewell DP: Respiratory burst activity of intestinal macrophages in normal and inflammatory bowel disease. Gut 30:1362–1370, 1989
Suematsu M, Suzuli M, Kitahora T, Miru S, Suzuki K, Hibi T, Watanabe M, Nagata H, Asakura H, Tsuchiya M: Increased respitatory burst of leeukocytes in inflammatory bowel diseases—the analysis of free radical generation by using chemiluminenscence probe. J Clin Lab Immunol 24:125–128, 1987
Schreiber S, MacDermott RP, Raedler A, Pinnau R, Bertovich MJ, Nash GS: Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease. Gastroenterology 101:1020–1030, 1991.
Grisham MB, Granger DN: Mechanisms of neutrophil-mediated tissue injury.In Current Topics in Gastroenterology—Inflammatory Bowel Disease. RP McDermott, WF Stenson (eds). New York, Elsevier Science Publishing, 1992, pp 225–239
von Ritter C, Sekizuka E, Grisham MB, Granger DN: The chemotactic peptideN-formyl-methionyl-leucyl-phenylalanine increases mucosal permeability in the distal ileum of the rat. Gastroenterology 95:651–656, 1988
von Ritter C, Grisham MB, Hoellwarth ME, Inauen W, Granger DN: Neutrophil-derived oxidants mediateN-formylmethionyl-leucyl-phenylalanine-induced ileitis in the rat. Gastroenterology 97:778–780, 1989
von Ritter C, Grisham MB, Granger DN: Sulfasalazine metabolites and dapsone attenuateN-formyl-methionyl-leucylphenylalanine-induced mucosal injury in rat ileum. Gastroenterology 96:811–816, 1989
Skoglund G, Cotgreave I, Rincon J, Patarroyo M, Ingelman-Sundberg M: H2O2 activates CD116/Cd18-dependent cell adhesion. Biochem Biophys Res Commun 157:443–449, 1988
Sekizuka E, Benoit JN, Grisham MB, Granger DN: Dimethylsulfoxide attenuates leukocyte adherence in mesenteric venules. Am J Physiol 256:H594-H597, 1989
Stevens C, Walz G, Chandler S, Lipman ML, Zanker B, Muggia A, Antonioli D, Peppercorn MA, Strom TB: Tumor necrosis factor-α, interleukin-1β, and interleukin-6 in inflammatory bowel disease. Dig Dis Sci 37(6):818–826, 1992
Issacs K, Sartor RB, Haskill JS: Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology 103(5):1587–1595, 1992
Chaudri G, Clark IA: Reactive oxygen species facilitate thein vitro andin vivo lipopolysaccharide-induced of tumor necrosis factor. J Immunol 143(4):1290–1294, 1989
Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA, Fiers W: Cytotoxicity activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. J Biol Chem 267:5317–5323, 1992
De Forge LE, Preston AM, Takeuchi E, Kenney J, Boxer LA, Remick DG: Regulation of interleukin-8 gene expression by oxidant stress. J Biol Chem 268(34):25568–25576, 1993
Bashir S, Gilmour H, Denman MA, Blake DR, Winyard PG: Oxidative DNA damage and cellular sensitivity to oxidative stress in human autoimmune diseases. Ann Rheum Dis 52:659–666, 1993
Kuchino Y, Mori F, Kasai H, et al: Misreading of DNA templates containing 8-hydroxydcoxyguanosine at the modified base and at adjacent residues. Nature 327:77–79, 1987
Harris G: DNA damage and repair of immunologically active cells. Immunol Today 4:109–112, 1983
Shalon L, Gulwani-Akolkar B, Fisher SE, Akolkar PN, Panja A, Mayer L, Silver J: Evidence for an altered T-cell receptor repertiore in Crohn's disease. Autoimmunity 17:241–248, 1994
Gulwani-Alokar B, Alokar RN, Cerchia R, McKinley M, Fisher SE, Silver J: Crohn's disease is accompanied by changes in CD4+, but not CD8+, T-cell receptor of lamina propria lymphocytes. Clin Immunol Immunopathol 77:95–106, 1995
Riordan JF: Biochemistry of zinc. Med Clin North Am 60:661–674, 1976
Samuni A, Chevion M, Czatski G: Unusual copper induced sensitization of the biological damage due to superoxide radicals. J Biol Chem 256:12632–12635, 1981
Mulder TP, Verspaget HW, Janssens AR, de Bruin PA, Penna AS, Lamers CV: Decrease in two intestinal copper-zinc containing proteins with antioxidant function in inflammatory bowel disease. Gut 32(10):1146–1150, 1991
Verspaget HW, Pena AS, et al: Diminished neutrophil function in Crohn's disease and ulcerative colitis identified by decreased oxidative metabolism and low superoxide dismutase content. Gut 29:223–228, 1988
Bray TM, Bettger WJ: The physiologic role of zinc as an antioxidant. Free Radic Biol Med 8:281–291, 1990
Powell SR, Hall D, Aiuto L, Wapnir RA, Teichberg S, Tortalani AJ: Zinc improves postischemic recovery of the isolated rat heart through inhibition of oxidative stress. Am J Physiol Heart Circ Physiol 1996 (in press)
Powell SR, Tortolani AJ: Recent advances in the role of reactive oxygen intermediates in ischemic injury. J Surg Res 53(4):417–429, 1992
Goldstein S, Czapski G: The role and mechanism of metal ions and their complexes in enhancing damage in biological systems or in protecting these systems from the toxicity of O −2 . Free Radic Biol Med 2:3–11, 1986
Aronovitch J, Godinger D, Samuni R, Czapski G (eds): Oxygen radicals in chemistry and biology. Berlin, Walter de Gruyter, 1984, pp 219–223
Babbs CF: Oxygen radicals in ulcerative colitis. Free Radic Biol Med 13:169–181, 1992
Stadtman ER: Metal ion-catalyzed oxidation of proteins: Biochemical mechanism and biological consequences. Free Radic Biol Med 9:315–325, 1990
Maskos ZK, Oppenol WH: Oxyradicals and multivitamin tablets. Free Radic Biol Med 11:609–610, 1991
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This work was supported in part by the Joe and Emily Lowe Foundation, Reach Out for Youth with Ileitis and Colitis, and a gift from Ruth and Leonard Litwin. Dr. Mullin is the recipient of a Career Development Award from the Crohn's and Colitis Foundation of America and an Investigator's Award from the American College of Gastroenterology.
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Lih-Brody, L., Powell, S.R., Collier, K.P. et al. Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease. Digest Dis Sci 41, 2078–2086 (1996). https://doi.org/10.1007/BF02093613
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DOI: https://doi.org/10.1007/BF02093613
Key words
- oxygen free radicals
- inflammation
- tissue injury
- inflammatory bowel disease
- antioxidants