Pentoxifylline attenuates mucosal damage in an experimental model of rat colitis by modulating tissue biomarkers of inflammation, oxidative stress, and fibrosis

Pentoxifylline attenuates mucosal damage in an experimental model of rat colitis by modulating tissue biomarkers of inflammation, oxidative stress, and fibrosis

Background/aim: This study was designed to identify the effect of pentoxifylline on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Materials and methods: Forty-two female Wistar rats were randomly divided into 7 groups: group A, TNBS + intraperitoneal (IP) pentoxifylline; group B, TNBS + IP saline; group C, TNBS + intrarectal (IR) pentoxifylline; group D, TNBS + IR saline; group E, IP pentoxifylline + TNBS; group F, IP saline + TNBS; group G, IR saline. Pentoxifylline was given daily for 3 days before or 6 days after the induction of colitis. Rats were killed after 6 days. Results: IP and IR pentoxifylline similarly and significantly reduced damage and histopathological scores. Pentoxifylline attenuated the accumulation of malonyldialdehyde and transforming growth factor β1 and the activities of myeloperoxidase, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinases-1, and it also restored superoxide dismutase activity. The IP route was more effective than the IR route in this regard. Administration of IP pentoxifylline before or after induction did not influence all parameters. Conclusions: Pentoxifylline showed a therapeutic effect in this experimental colitis model. IP administration seemed to be better. This effect may occur as a result of inhibition of oxidative stress and metalloproteinase activity.

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  • 1. Targan SR. Current limitations of IBD treatment: Where do we go from here? Ann N Y Acad Sci 2006; 1072: 1-8.
  • 2. Braegger CP, Nicholls S, Murch SH, Stephens S, Macdonald TT. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet 1992; 339: 89-91.
  • 3. Reimund JM, Wittersheim C, Dumont S, Muller CD, Baumann R,  Poindron P,  Duclos B. Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn’s disease. J Clin Immunol 1996; 103: 144-150.
  • 4. Peyrin-Biroulet L, Deltenre P, de Suray N, Branche J, Sandborn WJ, Colombel JF. Efficacy and safety of tumor necrosis factor antagonists in Crohn’s disease: meta-analysis of placebo controlled trials. Clin Gastroenterol Hepatol 2008; 6: 644-653.
  • 5. Danese S, Fiorino G, Peyrin-Biroulet L. Biological agents for moderately to severely active ulcerative colitis: a systematic review and network metaanalysis. Ann Intern Med 2014 ; 160: 704-711.
  • 6. Bessler H, Gilgal R, Djaldetti M, Zahavi I. Effects of pentoxifylline on the phagocytic activity, cAMP levels and superoxide anion production by monocytes and polymorphonuclear cells. J Leukocyte Biol 1986; 40: 747-757.
  • 7. Tannenbaum CS, Hamilton TA. Lipopolysaccharideinduced gene expression in murine peritoneal macrophages is selectively suppressed by agents that elevate intracellular cAMP. J Immunol 1980; 142: 1274-1280.
  • 8. Morris GP, Beck PL, Herridge MS. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 1989; 96: 795-780.
  • 9. Ackerman Z, Karmeli F, Cohen P, Rachmilewitz D. Experimental colitis in rats with portal hypertension and liver disease. Inflamm Bowel Dis 2003; 9: 18-24.
  • 10. Peterson TC, Peterson MR, Raoul JM. The effect of pentoxifylline and its metabolite-1 on inflammation and fibrosis in the TNBS model of colitis. Eur J Pharmacol 2011; 662: 47-54.
  • 11. Peterson TC, Davey K. Effect of acute pentoxifylline treatment in an experimental model of colitis. Aliment Pharmacol Ther 1997; 11: 575-580.
  • 12. Murthy S, Cooper HS, Yoshitake H, Meyer C, Meyer CJ, Murthy NS. Combination therapy of pentoxifylline and TNFα monoclonal antibody in dextran sulphate-induced mouse colitis. Aliment Pharmacol Ther 1999; 13: 251-260.
  • 13. Reimund JM, Dumont S, Muller CD, Kenney JS, Kedinger M, Baumann R, Poindron P, Duclos B. In vitro effects of oxpentifylline on inflammatory cytokine release in patients with inflammatory bowel disease. Gut 1997; 40: 475-480.
  • 14. Bauditz J, Haemling J, Ortner M, Lochs H, Raedler A, Schreiber S. Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn’s disease. Gut 1997; 40: 470-474.
  • 15. Abreu MT. Anti-TNF failures in Crohn’s disease. Gastroenterol Hepatol 2011; 7: 37-39.
  • 16. Schultz J, Kaminker K. Myeloperoxidase of the leucocyte of normal human blood. I. Content and localization. Arch Biochem Biophys 1962; 96: 465-467.
  • 17. D’Odorico A, Bortolan S, Cardin R, D’Inca R,  Martines D,  Ferronato A,  Sturniolo GC. Reduced plasma antioxidant concentrations and increased oxidative DNA damage in inflammatory bowel disease. Scand J Gastroenterol 2001; 36: 1289-1294.
  • 18. Vallance BA, Gunawan MI, Hewlett B, Bercik P, Van Kampen C,  Galeazzi F,  Sime PJ,  Gauldie J, Collins SM. TGF-β1 gene transfer to the mouse colon leads to intestinal fibrosis. Am J Physiol Gastrointest Liver Physiol 2005; 289: 116-128.
  • 19. Von Lampe B, Barthel B, Coupland SE, Riecken EO, Rosewicz S. Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease. Gut 2000; 47: 63-73.
  • 20. Keshavarzian A, Banan A, Farhadi A, Komanduri S,  Mutlu E, Zhang Y, Fields JZ. Increases in free radicals and cytoskeletal protein oxidation and nitration in the colon of patients with inflammatory bowel disease. Gut 2003; 52: 720-728.
  • 21. Bernstein CN. Treatment of IBD: where we are and where we are going. Am J Gastroenterol 2015; 110: 114-126.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
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