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Effect of Diet on Changes in Small Intestinal Blood Flow Following Intracolonic Administration of Indomethacin to Rats

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Abstract

Liquid diet (LD) is known to be protective against indomethacin-induced enteropathy, which is thought to be associated with ischemic change. We tested the hypothesis that the solid component of diet modulates small intestinal blood flow (SIBF) following indomethacin administration. In the first experiment, male Wistar rats were divided into 18-hr-fasted and normal diet groups. Indomethacin (20 mg/kg) or vehicle was administered intracolonically. SIBF was measured on both the mesenteric and antimesenteric sides of the intestine, using the hydrogen gas clearance method. In the second experiment, rats were given LD alone or LD with increasing concentration of soluble/insoluble fiber for seven days. The baseline SIBF was significantly higher in the groups with normal diet and LD with fiber than in the fasting and LD groups. Following indomethacin administration, SIBF gradually decreased in the groups with normal diet and LD with insoluble fiber, while neither liquid diet nor fasting reduced SIBF. There was no difference in SIBF between the mesenteric and antimesenteric sides of the intestine in any group. Our findings suggest that solid components of diet increase basal SIBF and decrease SIBF following indomethacin administration.

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REFERENCES

  1. Bjarnason I, Hayllar J, MacPherson AJ, Russell AS: Side effects of non-steroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 104:1832–1847, 1993

    Google Scholar 

  2. Robert A, Asano T: Resistance of germ free rats to indomethacin-induced intestinal lesions. Prostaglandins 14:333–341, 1977

    Google Scholar 

  3. Satoh H, Guth PL, Grossman MI: Role of bacteria in gastric ulceration produced by indomethacin in the rat: Cytoprotective action of antibiotics. Gastroenterology 84:483–489, 1983

    Google Scholar 

  4. Reuter BK, Davies NM, Wallace JL: Nonsteroidal antiinflammatory drug enteropathy in rats: role of permeability, bacteria, and enterohepatic circulation. Gastroenterology 112:109–117, 1997

    Google Scholar 

  5. Wax J, Clinger WA, Varner P, Bass P, Winder CV: Relationship of the enterohepatic cycle to ulcerogenesis in the rat small bowel with flufenamic acid. Gastroenterology 58:772–780, 1970

    Google Scholar 

  6. Satoh H, Inada I, Hirata T, Maki Y: Indomethacin produces gastric antral ulcers in the refed rat. Gastroenterology 81:719–725, 1981

    Google Scholar 

  7. Satoh H, Paul H, Morton IG: Role of food in gastrointestinal ulceration produced by indomethacin in the rat. Gastroenterology 83:210–215, 1982

    Google Scholar 

  8. Matsumoto T, Iida M, Nakamura S, Hizawa K, Kuroki F, Fujishima M: An animal model of longitudinal ulcers in the small intestine induced by intracolonically administered indomethacin in rats. Gastroenterol Jpn 28:10–17, 1993

    Google Scholar 

  9. Matsumoto T, Iida M, Kuroki F, Hizawa K, Koga H, Fujishima M: Effect of diet on experimentally induced intestinal ulcers in rats: Morphology and tissue leukotrienes. Gut 35:1058–1063, 1994

    Google Scholar 

  10. Whittle BJR: Mechanism underlying gastric mucosal damage induced by indomethacin and bile-salts, and the actions of prostaglandins. Br J Pharmacol 60:455–460, 1977

    Google Scholar 

  11. Ashley SW, Sonnenschein LA, Cheung LY: Focal gastric mucosal blood flow at the site of aspirin-induced ulceration. Am J Surg 149:53–59, 1985

    Google Scholar 

  12. Kitahora T, Guth PH: Effect of aspirin hydrochloric acid on the gastric mucosal microcirculation. Gastroenterology 93;810–817, 1987

    Google Scholar 

  13. Arakawa T, Nakamura H, Chono S, Satoh H, Fukuda T, Saek Y, Kobayashi K: Absence of effect of 16,16-dimethyl prostaglandin E2 on reduction of gastric mucosal blood flow caused by indomethacin in rats. Dig Dis Sci 34:1369–1373, 1989

    Google Scholar 

  14. Lu YF, Mizutani M, Neya T, Nakayama S: Indomethacin-induced lesion modifies contractile activity in rat small intestines. Scand J Gastroenterol 30:445–450, 1995

    Google Scholar 

  15. Takeuchi K, Okada M, Niida H, Okabe S: Possible mechanisms involved in gastric hypermotility caused by indomethacin in the rat: role of glycoprivic response. Dig Dis Sci 35:984–992, 1990

    Google Scholar 

  16. Brodie DA, Cook PG, Bauer BJ: Indomethacin-induced intestinal lesions in the rat. Toxicol Appl Pharmacol 17:615–624, 1970

    Google Scholar 

  17. Fang W, Broughton A, Jacobson ED: Indomethacin-induced intestinal inflammation. Dig Dis Sci 22:749–760, 1977

    Google Scholar 

  18. Wallace JL, Keenman CM, Granger DN: Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophil-dependent process. Am J Physiol 259:G462–467, 1990

    Google Scholar 

  19. Brand JS, Morise Z, Tagerud S, Mazzola L, Granger DN, Grisham MB: Role of the proteasome in rat indomethacininduced gastropathy. Gastroenterology 116:865–873, 1999

    Google Scholar 

  20. Newberry RD, Stenson WF, Lorenz RG: Cyclooxygenase-2-dependent arachidonic acid metabolites are essential modulators of the intestinal immune response to dietary antigen. Nature Med 5:900–906, 1999

    Google Scholar 

  21. Anthony A, Dhillon AP, Nygard G, Hudson M, Piasecki C, Strong P, Trevethick MA, Clayton NM, Jordan CC, Pounder RE, Wakefield AJ: Early histological features of small intestinal injury induced by indomethacin. Aliment Pharmacol Ther 7:29–40, 1993

    Google Scholar 

  22. Nygard G, Anthony A, Piasecky C, Trevethick MA, Hudson M, Dhillon AP, Pounder RY, Wakefield AJ: Acute indomethacininduced jejunal injury in the rat: early morphological and biochemical changes. Gastroenterology 106:567–575, 1994

    Google Scholar 

  23. Anthony A, Dhillon AP, Thrasivoulou C, Pounder RE, Wakefield AJ: Pre-ulcerative villous contraction and microvascular occlusion induced by indomethacin in the rat jejunum: A detailed morphological study. Aliment Pharmacol Ther 9:605–613, 1995

    Google Scholar 

  24. Anthony A, Sim R, Dhillon AP, Pounder RE, Wakefield AJ: Gastric mucosal contraction and vascular injury induced by indomethacin precede neutrophil infiltration in the rat. Gut 39:363–368, 1996

    Google Scholar 

  25. Battarbee HD, Grisham MB, Johnson GG, Zavecz JH: Superior mesenteric artery blood flow and indomethacin-induced intestinal injury and inflammation. Am J Physiol 271:G605–G612, 1996

    Google Scholar 

  26. Ligumsky M, Sestieri M, Karmeli F, Zimmerman J, Okon E, Rachmilewitz D: Rectal administration of nonsteroidal antiin-flammatory drugs-effect on rat gastric ulcerogenicity and prostaglandin E2 synthesis. Gastroenterology 98:1245–1249, 1990

    Google Scholar 

  27. Aukland K, Bower BF, Berliner RW: Measurements of local blood flow with hydrogen gas. Circ Res 14:164–187, 1964

    Google Scholar 

  28. Gallavan RH Jr, Chou CC: Possible mechanisms for the initiation and maintenance of postprandial intestinal hyperemia. Am J Physiol 249:G301–G308, 1985

    Google Scholar 

  29. Chou CC, Grassmick B: Motility and blood flow distribution within the wall of the gastrointestinal tract. Am J Physiol 235:H34–H39, 1978

    Google Scholar 

  30. Alemany CA, Stonestreet BS: Effect of nitric oxide synthesis inhibition on mesenteric perfusion in young pigs. Am J Physiol 272:G612–G616, 1997

    Google Scholar 

  31. Gallavan RH Jr, Chou CC: Prostaglandin synthesis inhibition and postprandial intestinal hyperemia. Am J Physiol 242:G140–G146, 1982

    Google Scholar 

  32. Proctor KG: Differential effect of cyclooxygenase inhibitors on absorptive hyperemia. Am J Physiol 249:H755–H762, 1985

    Google Scholar 

  33. Chou CC, Alemayehu A, Mangino MJ: Prostanoids in regulation of postprandial jejunal hyperemia and oxygen uptake. Am J Physiol 257:G798–G808, 1989

    Google Scholar 

  34. Goto H, Kanamori S, Hayakawa T, Sugiyama S, Ozawa T: Effect of dietary fiber on prostanoid concentrations in cecal mucosa of rats. Biochem Mol Biol Int 38:437–443, 1996

    Google Scholar 

  35. Holm L, Jagare A: Influence of tactile stimulation of the rat gastric mucosa on blood flow and acid output. Am J Physiol 265:G303–G309, 1993

    Google Scholar 

  36. Ellis PR, Roberts FG, Low AG, Morgan LM: The effect of high-molecular-weight guar gum on net apparent glucose absorption and net apparent insulin and gastric inhibitory polypeptide production in the growing pig: Relationship to rheological changes in jejunal digesta. Br J Nutr 74:539–556, 1995

    Google Scholar 

  37. Anthony A, Pounder RE, Dhillon AP, Wakefield AJ: Vascular anatomy defines sites of indomethacin-induced jejunal ulceration along the mesenteric margin. Gut 41:763–770, 1997

    Google Scholar 

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Authors and Affiliations

  1. Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Japan

    Chifumi Yamamoto, Keishi Kawakubo, Kunihiko Aoyagi, Takayuki Matsumoto, Mitsuo Iida, Setsuro Ibayashi, Takanari Kitazono, Kosei Doi, Koki Kanamoto & Masatoshi Fujishima

  2. Division of Gastroenterology, Department of Medicine, Kawasaki Medical School, Kurashiki, Japan

    Chifumi Yamamoto, Keishi Kawakubo, Kunihiko Aoyagi, Takayuki Matsumoto, Mitsuo Iida, Setsuro Ibayashi, Takanari Kitazono, Kosei Doi, Koki Kanamoto & Masatoshi Fujishima

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  1. Chifumi Yamamoto
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  2. Keishi Kawakubo
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  3. Kunihiko Aoyagi
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  4. Takayuki Matsumoto
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Yamamoto, C., Kawakubo, K., Aoyagi, K. et al. Effect of Diet on Changes in Small Intestinal Blood Flow Following Intracolonic Administration of Indomethacin to Rats. Dig Dis Sci 46, 200–207 (2001). https://doi.org/10.1023/A:1005529016641

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