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Agents capable of eliminating reactive oxygen species

Catalase, WR-2721, or Cu(II)2(3,5-DIPS)4 decrease experimental colitis

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Abstract

Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide, hydroxyl radical, and hypochlorous acid have been implicated in the pathogenesis of inflammation and tissue injury in colitis. To determine whether or not anti-ROS agents can decrease the severity of colitis, we evaluated the effects of three known anti-ROS agents: catalase, WR-2721, and Cu(II)2(3,5-DIPS)4 on acetic acid-induced colonic inflammation in rats. Histologically, all three compounds significantly decreased the severity of colonic inflammation. The anti-ROS activity of these compounds was also tested using the luminol-enhanced chemiluminescence assay. Catalase, WR-2721, or Cu(II)2(3,5-DIPS)4 significantly inhibited luminol-enhanced chemiluminescence produced by inflamed colonic mucosa. These findings suggest that ROS, and in particular superoxide, hydrogen peroxide, and/or one of its secondarily derived species, may play an important role in acetic acid-induced colitis. Further studies are needed to determine the potential effectiveness of these compounds in human colitis.

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References

  1. Kirsner JB, Shorter RG: Recent development in “nonspecific” inflammatory bowel disease. N Engl J Med 306:775–784, 1982

    Google Scholar 

  2. McDonaldson RM: Crohn's disease.In Gastrointestinal Diseases. MH Sleisenger, JS Fordtran (eds). Philadelphia, WB Saunders, 1989, pp 1327–1358

    Google Scholar 

  3. Sharon P, Stenson W: Metabolism of arachidonic acid in acetic acid colitis in rats. Gastroenterology 88:55–63, 1985

    Google Scholar 

  4. Wallace JL, Whittle BJR, Boughton-Smith NK: Prostaglandin protection of rat colonic mucosa from damage induced by ethanol. Dig Dis Sci 30:866–876, 1985

    Google Scholar 

  5. Keshavarzian A, Morgan G, Sedghi S, Gordon JH, Doria M: Role of reactive oxygen species in experimental colitis. Gut 31:786–790, 1990

    Google Scholar 

  6. Parks D, Buckley G, Granger N: Role of oxygen free radicals in digestive tract disease. Surgery 94:415–422, 1983

    Google Scholar 

  7. Suematsu M, Suzuk M, Kitahora T, Miura S, Suzki K, Mibi T, Watanabe M, Nagata H, Asakura H, Tsuchiya M: Increase respiratory burst of leukocytes in inflammatory bowel disease. The analysis of free radicals generation by using chemiluminescence probe. J Clin Lab Immunol 24:125–128, 1987

    Google Scholar 

  8. Bukave K, Laursen LS, Lauritsen K, Rask-Madsen J, Naesdal J, Jacobsen O, Goebell H, Peskar B, Cort D, Stenson W, Hanauer S: 5-lipoxygenase inhibition in doubleblind trial with Zileuton: How much is sufficient in active ulcerative colitis? Gastroenterology 100:A200, 1991

    Google Scholar 

  9. Aruoma OL, Wasil M, Halliwell B, Hoey BM, Butler J: The scavenging of oxidants by sulfasalazine and its metabolites: A possible contribution to their anti-inflammatory effects. Biochem Pharmacol 36:3739–3742, 1987

    Google Scholar 

  10. Delsoldato P, Campier MA, Brignola C, Bazzocchi G, Gionchetti P, Lanfranchi GA, Tamba M: A possible mechanism of action of sulfasalazine and 5-amino salicylic acid in inflammatory bowel disease: Interaction with oxygen free radicals. Gastroenterology 89:1215–1216, 1985

    Google Scholar 

  11. Craven PA, Pfanstiel J, Reisuke S, DeRubertis FR: Actions of sulfasalazine and 5-aminosalicylic acid as reactive oxygen scavengers in the suppression of bile acid-induced increases in colonic epithelial cell loss and proliferative activity. Gastroenterol 92:1998–2008, 1987

    Google Scholar 

  12. Ahnfelt-Ronne I, Nielsen OH, Christensen A, Langholz E, Binder V, Riis P: Clinical evidence supporting the radical scavenger mechanism of 5-aminosalicylic acid. Gastroenterology 98:1162–1169, 1990

    Google Scholar 

  13. Emerit J, Loeper J, Chomette G: Superoxide dismutase in the treatment of post radiotherapeutic necrosis and of Crohn's disease. Bull Eur Physiol Pathol Respir 17(suppl): 287–288, 1981

    Google Scholar 

  14. Weiss SJ: Tissue destruction by neutrophils. N Engl J Med 320:365–376, 1989

    Google Scholar 

  15. Grisham M, McCord J: Chemistry and cytotoxicity of reactive oxygen metabilites.In Physiology of Oxygen Radicals. A Taylor, S Matalon, P Wared (eds). Bethesda, Maryland, American Physiology Society, 1986, pp 1–18

    Google Scholar 

  16. MacPherson B, Pfeiffer C: Experimental colitis. Digestion 14:424–452, 1976

    Google Scholar 

  17. Halliwell B: Biochemical mechanisms accounting for the toxic action of oxygen on living organisms: The key role of superoxide dismutase. Cell Biol Int Rep 2(2):113–128, 1978

    Google Scholar 

  18. Fantone J, Ward P: Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol 107:397–418, 1982

    Google Scholar 

  19. Selim Karayaicin S, Sturbaum W, Wachsman JT, Cha JH, Powell DW: Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport. J Clin Invest 86:60–68, 1990

    Google Scholar 

  20. Reed GA, Madhu C: Peroxide scavenging by Cu(II) sulfate and Cu(II)(3,5-diisopropylsalicylate)2.In Biology of Copper Complexes. JRJ Sorenson (ed). Clifton, New Jersey, Humana Press, 1987, pp 287–298

    Google Scholar 

  21. Sorenson JRJ: Copper complexes offer a physiological approach to treatment of chronic diseases. Prog Med Chem 26:437–568, 1989

    Google Scholar 

  22. Kanofsky JR: Singlet oxygen production by lactoperoxidase evidence from 1270 nm chemiluminescence. J Biol Chem 258:5991–5993, 1983

    Google Scholar 

  23. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254, 1976

    Google Scholar 

  24. Vaille A, Jadot G, Elizagaray A: Anti-inflammatory activity of various superoxide dismutases on polyarthritis in the Lewis rat. Biochem Pharmacol 39(2):247–255, 1990

    Google Scholar 

  25. Michelson AM, Jadot G, Puget K: Mechanism of antiinflammatory activity of superoxide dismutase.In The Biological Role of Reactive Oxygen Species in Skin. O Hayashu, S Imamura, Y Miyachi (eds). Tokyo, University of Tokyo Press, 1987, pp 199–210

    Google Scholar 

  26. Wasil M, Halliwell B, Hutchison DCS, Baum H: The antioxidation of human extra cellular fluids: Effect of human serum and its protein components on the inactivation of antiprotienase by hypochlorous acid and by hydrogen peroxide. Biochem J 243:219–223, 1987

    Google Scholar 

  27. Aruoma OI, Halliwell B: Action of hypochlorous acid on the antioxidant protective enzymes superoxide dismutase, catalase and glutathione peroxidase. Biochem J 248:976–976, 1987

    Google Scholar 

  28. Ayene SI, Srivastava PN: Effect of WR-2721 on radiationinduced lipid peroxidation and enzyme release in erythrocytes and microsomes. Int J Radiat Biol 56:265–275, 1989

    Google Scholar 

  29. Weiss JF, Hoover RL, Kumar KS: selenium pretreatment enhances the radioprotective effect and reduces the lethal toxicity of WR-2721. Free Radic Res Commun 3:33–38, 1987

    Google Scholar 

  30. Shaw LM, Glover D, Turris A, Brown DO, Bonner HS, Norfleet AL, Weiler C, Blick JM, Kligerman MM: Pharmacokinetics of WR-2721. Pharmacol Ther 39:195–201, 1988

    Google Scholar 

  31. Millar JL, mcElavain TJ, Clutterbuck RD, Wist EA: The modification of Melphalan toxicity in tumor bearing mice by WR-2721. Am J Clin Oncol 5:321–328, 1982

    Google Scholar 

  32. Yuhas JM: On the potential application of radioprotective drugs in solid tumor radiotherapy.In Radiation-Drug Interactions in the Treatment of Cancer, GH Sokol, RP Maickel (eds). New York, Wiley & Sons, 1980, pp 113–135

    Google Scholar 

  33. France H, Jirtle R, Mansbach C: Intracolonic WR-2721 protection of the rat colon from acute radiation injury. Gastroenterology 91:644–650, 1986

    Google Scholar 

  34. Calabro-Jones PM, Fahey RC, Smoluk GD, Ward JF: Alkaline phosphatase promotes radioprotective effects of the transported from of the drug. Cancer Res 48:3641–3647, 1988

    Google Scholar 

  35. Nagy B, Dale PJ, Grdina DJ: Protection againstcis-diaminedicholorplatinum cytotoxicity and mutagenicity in V79 cells by 2-[(aminopropy)amino] ethanethiol. Cancer Res 46:1132–1135, 1986

    Google Scholar 

  36. Roch-Arveiller M, Revellent V, Pham Huy D, Maman L, Fontagne J, Sorenson JRJ, Giroud JP: Effects of some non-steroidal anti-inflammatory drug copper complexes on polymorphonuclear leukocyte oxidative metabolism. Agents Actions 31:65–71, 1990

    Google Scholar 

  37. Sorenson JRJ, Soderberg LSF, Chidambaram MV, de la Rosa DT, Salari H, Bond K, Kearns GL, Gray RA, Epperson CE, Baker ML: Bioavailable copper complexes offer a physiologic approach to treatment of chronic disease. Adv Exp Med Biol 258:229–234, 1989

    Google Scholar 

  38. Okuyama S, Hashimoto S, Aihara H, Willingham WM, Sorenson JRJ: copper complexes of non-steroidal antiinflammatory agents: Analgesic activity and possible opioid receptor activation. Agents Actions 21:130–144, 1987

    Google Scholar 

  39. Sorenson JRJ: Bis(3,5-diisopropylsalicylato)copper(II), a potent radioprotectant with superoxide dismutase mimetic activity. J Med Chem 27:1747–1749, 1984

    Google Scholar 

  40. Soderberg LSF, Barnett JB, Baker ML, Chang LW, Salari H, Sorenson JRJ: Copper(II)2(3,5-diisopropylsalicylate)4 stimulates hemopoiesis in normal and irradiated mice. Exp Hematol 16:577–580, 1988

    Google Scholar 

  41. Weser U, Richter C, Wendel A, Younes M: Reactivity of antiinflammatory and superoxide dismutase active Cu(II)-salicylates. Bioinorganic Chem 8:201–213, 1978

    Google Scholar 

  42. Duran HA, de Rey BM: Differential oxidative stress induced by two different types of skin tumor promoters, benzoyl peroxide and 12-O-tetradecanoylphorbol-13-acetate. Carcinogenesis 12(11):2047–2052, 1991

    Google Scholar 

  43. Nilsson K: Effects of Cu(II)(3,5-diisoporopylasalicylate)2 on soluble protein kinase C activity in rat liver. Cancer Lett 47:169–177, 1989

    Google Scholar 

  44. Kensler TW, Trush MA: Inhibition of oxygen radical metabolism in phorbol ester-activated polymorphonuclear leukocytes by an antitumor promoting copper complex with superoxide dismutase-mimetic activity. Biochem Pharmacol 32:3485–3487, 1983

    Google Scholar 

  45. May PM, Linder PW, Williams DR: Ambivalent effect of protein binding on computed distributions of metal ions complexed with ligands in blood plasma. Experientia 32:1492–1493, 1976

    Google Scholar 

  46. Aruoma OL, Halliwell B, Gajewski E, Dizdaroglu M: Copper-ion-dependent damage to the bases in DNA in the presence of hydrogen peroxide. Biochem J 273:601–604, 1991

    Google Scholar 

  47. Farhataziz, Ross AB: Selected specific rates of reactions of transients from water in aqueous solution. III Hydroxyl radical and perhydroxyl radical and their radical ions. National Bureau of Standards, Reference Data System. National Bureau of Standards, US Department of Commerce, Washington, DC, pp 12–13, January 1977

    Google Scholar 

  48. Frenkel K, Blum F, Troll W: Copper ions and hydrogen peroxide form hypochlorite from NaCl thereby mimicking myeloperoxidase. J Cell Biochem 30:181–193, 1986

    Google Scholar 

  49. Cassone MC: Azione di salicilati sulla scomparsadi batteri (Lactobacillus casei) fagocitati da polimorfonucleati. Boll Soc Ital Biol Sper 58:371–377, 1982

    Google Scholar 

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Varzian, A.K., Haydek, J., Zabihi, R. et al. Agents capable of eliminating reactive oxygen species. Digest Dis Sci 37, 1866–1873 (1992). https://doi.org/10.1007/BF01308081

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