Abstract
The mechanism of tissue damage in ulcerative colitis (UC) is unknown. However, recent evidence suggests that reactive oxygen species (ROS) are critical mediators of inflammation, and tissue damage in UC and antioxidants could be beneficial in the treatment of UC. Our aim was to evaluate the effects of two new antioxidants, Zolimid and AEOL11201 on experimental colitis. Antioxidants or vehicle were given to rats for five days after induction of colitis by intrarectal administration of 4% acetic acid. Severity of colitis was assessed on day 5. Zolimid and AEOL11201 significantly improved acetic acid-induced colitis. Both Zolimid and AEOL11201 significantly decreased the severity of diarrhea, and severity of macroscopic and histological changes in the colon. Both agents also significantly decreased colonic MPO levels. In conclusion, Zolimid and AEOL11201 are effective antiinflammatory agents in an animal model of colitis. Further studies are needed to evaluate their beneficial therapeutic effects in patients with UC.
Similar content being viewed by others
REFERENCES
Kirsner JB, Shorter RG: Recent development in nonspecific inflammatory bowel disease. N Engl J Med 306:775–837, 1982
Babbs CF: Oxygen radicals in ulcerative colitis. Free Radic Biol Med 13:169–182, 1992
Grisham MB: Oxidants and free radicals in inflammatory bowel disease. Lancet 344:859–861, 1994
Sedgi S, Fields JZ, Klamut M, et al: Increased production of luminol enhanced chemiluminescence by the inflamed colonic mucosa in patients with ulcerative colitis. Gut 34:1191–1197, 1993
Simmonds NJ, Allen RE, Stevens TRJ, van Someren RNM, Blake DR, Rampton DS: Chemiluminescence assay of mucosal reactive metabolites in inflammatory bowel disease. Gastoenterology 103:186–196, 1992
Keshavarzian A, Sedghi S, Kanofsky J, et al: Excessive production of reactive oxygen metabolites by inflamed colon: Analysis by chemiluminescence probe. Gastroenterology 103,177–185, 1992
Grisham MB, Granger DN: Neutrophil mediated mucosal injury. Role of reactive oxygen metabolites. Dig Dis Sci 33(suppl):6S–15S, 1988
Keshavarzian A, et al: Mitomycin-C-induced colitis in rats: A new animal model of acute colonic inflammation implicating reactive oxygen species. J Lab Clin Med 120:778–791, 1992
Keshavarzian A, Morgan NG, Sedghi S., Gordon JH, Doria M: Role of reactive oxygen metabolites in experimental colitis. Gut 31:786–790, 1990
Emerit J, Pelletier S, Likforman J, Pasquier C, Thuillier A: Phase II trial of superoxide dismutase (CuZn SOD) in the treatment of crohn' disease. Free Radic Res Commun 12-13(Pt 2): 563–569, 1991
Levin KE, Pemberton JH, Phillips SF, Zinsmeister AR, Pezim ME: Role of oxygen free radicals in the etiology of pouchitis. Dis Colon Rectum 35:452–456, 1992
Keshavarzian A, Haydek J. Zabihi R, et al: Agents capable of eliminating reactive oxygen species. Catalase, WR-2721, or Cu(II)2(3,5-DIPS)4 decrease experimental colitis. Dig Dis Sci. 37(12):1866–1873, 1992
Yoshikawa T, Takahashi S, Kondo M: Possible role of free radicals in chronic inflammation in the gut. EXS 62:353–358, 1992
Simmonds NJ: Reactive oxygen metabolites and inflammatory bowel diseases. Doctor of Medicine, thesis. Oxford, Oxford University, 1992
Simmonds NJ, Blake DR, Rampton DS: The effects of amino salicylates and potential new drugs on mucosal reactive oxygen metabolite production in ulcerative colitis. Gut 33(suppl):S7, 1992
Yavuz Y, Yuksel M, Yegen BC. Alican I: The effect of antioxidant therapy on colonic inflammation in the rat. Res Exp Med 199(2):101–110, 1999
Koksoy FN, Kose H, Soybir GR, Yalcin O, Cockneseli B: The prophylactic effects of superoxide dismutase, catalase, desferrioxamine, verapamil and disulfuram in experimental colitis. J R Coll Surg Edinburgh 42(1):27–30, 1997
Viau AT, Abchowski A, Greenspan S, Davis FF: Safety evaluation of free radical scavengers PEG-catalase and PEGsuperoxide dismutase. J Free Radic Biol Med 2(4):283–288, 1986
MacPherson BR, Pfeiffer CJ: Experimental production of diffuse colitis in rats. Digestion 17:135–150, 1978
Millar AD, Rampton DS, Chander CL, Claxson AW, Blades S, Coumbe A, Panneta J, Morris CJ, Blake DR: Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut 39(3):407–415, 1996
Krawisz JE, Sharon P., Stenson WF: Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gastroenterology 87:1344–1350, 1984
Babizhayev MA, Seguin MC, Gueyne J, Evstigneeva RP, Ageyeva EA, Zheltukhina GA: L-Carnosine(eta-alanyl-Lhistidine) and carcinine (beta-alanylhistamine) act as natural antixodiants with hyroxyl-radical-scavenging and lipid peroxidase activities. Biochem J 304(pt 2):509–516, 1994
Chan WK, Decker EA, Chow CK, Biossonnealut GA: Effect of dietary carnosine on plasma and tissue antioxidant concentration and on lipid oxidation in rat skeletal muscle. Lipids 29(7):461–466, 1994
Kukreja RC, Hess ML: The oxygen free radical system: from equations through membrane-protein interactions to cardiovascular injury and protection. Cardiovasc Res 26(7):641–655, 1992
Patel M, Day BJ: Metalloporphyrin class of therapeutic catalytic antioxidants. Trends Pharmacol Sci 20:359–364, 1999
Day BJ, Batinic-Haberle I, Crapo JD: Metalloporphyrins are potent inhibitors of lipid peroxidation. Free Radic Biol Med 26:730–736, 1999
Udilova N, Popov IN, Levin GI, Vladimirov IA: Antioxidant properties of UC irradiated blood plasma as determined by the photochemiluminescence method. Biofizika 42(1):187–190, 1997
Yokoyama H, Horie T, Awazu S: Lipid peroxidation and chemiluminescence during naproxen metabolism in rat liver microsomes. Hum & Exp Toxicol 13(12):831–838, 1994
Kirsner JB, Shorter RG: Recent developments in “nonspecific” inflammatory bowel disease. N Engl J Med 306:837–848, 1982
Sharon P, Stenson WF: Metabolism of arachonic acid in acetic acid. Similarity to human inflammatory bowel disease. Gastroenterology 88:55–63, 1985
Hodgson HJF, Jewell DP: The humoral immune system in inflammatory bowel disease. Am J Dig Dis 23:123–128, 1978
Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL: Hapten induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803, 1989
Repine JE, Eaton JW, Anders MW, Hoidal JR, Fox RB: Generation of hydroxyl radical by enzymes, chemicals and human phagocytes in vitro. Detection with the anti-inflammatory agent dimethyl sulphoxide. J Clin Invest 64:1642–1651, 1979
Fitzpatrick LR, Bostwick JS, Renzetti M, Pendleton RG, Decktor DL: Antiinflammatory effects of various drugs on acetic acid induced colitis in the rat. Agents Actions. 30(3-4): 393–402, 1990
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Choudhary, S., Keshavarzian, A., Yong, S. et al. Novel Antioxidants Zolimid and AEOL11201 Ameliorate Colitis in Rats. Dig Dis Sci 46, 2222–2230 (2001). https://doi.org/10.1023/A:1011975218006
Issue Date:
DOI: https://doi.org/10.1023/A:1011975218006