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Diamine oxidase as a marker of intestinal mucosal injury and the effect of soluble dietary fiber on gastrointestinal tract toxicity after intravenous 5-fluorouracil treatment in rats

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Abstract

The level of plasma diamine oxidase (DAO) activity is associated with the maturation and integrity of small intestinal mucosa. This study in rats investigated whether a decreased level of plasma DAO could reflect the severity of mucosal injury due to intravenous 5-fluorouracil (5-FU) treatment. The beneficial effect of soluble dietary fiber (SDF) on preventing diarrhea after 5-FU treatment was also examined. To induce diarrhea, 5-FU (50 mg/kg/day for four days) was administered via the tail vein with or without SDF supplementation. After 5-FU treatment, the majority of rats developed moderate to severe diarrhea, and levels of plasma DAO activity significantly decreased compared to those of control group (P < 0.05). Scanning electron microscopy revealed disarrangement of the small intestinal villi. Contrarily, the rats supplemented with SDF had diarrhea less frequently (50.0 vs. 91.7 %, P = 0.025) on day five, and DAO activity levels were significantly higher than in those rats administered 5-FU alone (8.25 ± 5.34 vs. 5.50 ± 4.32, P = 0.023). In conclusion, plasma DAO activity decreases in response to severe intestinal mucosal injury after 5-FU treatment, and SDF supplementation might be a practical and useful treatment for reducing the intestinal toxicity of 5-FU.

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References

  1. Kusche J, Lorenz W, Schmidt J (1975) Oxidative deamination of biogenic amines by intestinal amine oxidases: histamine is specially inactivated by diamine oxidase. Hoppe-Seyler’s Z Physiol Chem 356:1485–1496

    Article  CAS  PubMed  Google Scholar 

  2. Jänne J, Pösö H, Raina A (1978) Polyamines in rapid growth and cancer. Biochim Biophys Acta 473:241–293

    PubMed  Google Scholar 

  3. Baylin SB, Stevens SA, Shakir KM (1978) Association of diamine oxidase and ornithine with maturing cells in rapidly proliferating epithelium. Biochim Biophys Acta 541:415–419

    Article  CAS  PubMed  Google Scholar 

  4. Maintz L, Novak N (2007) Histamine and histamine intolerance. Am J Clin Nutr 85:1185–1196

    CAS  PubMed  Google Scholar 

  5. D’Agostino L, Ciacci C, Capuano G, Daniele B, D’Agostino G, Barone MV, Rodino S, Budillon G, Mazzacca G (1986) Metabolic fate of plasma diamine oxidase: evidence of isolated and perfused rat liver uptake. Digestion 34:243–250

    Article  PubMed  Google Scholar 

  6. Shakir KM, Margolis S, Baylin SB (1977) Localization of histaminase (diamine oxidase) in rat small intestinal mucosa; site of release by heparin. Biochem Pharmacol 26:2343–2347

    Article  CAS  PubMed  Google Scholar 

  7. Bieganski T (1983) Biochemical, physiological and pathophysiological aspects of intestinal diamine oxidase. Acta Physiol Pol 34:139–154

    CAS  PubMed  Google Scholar 

  8. Luk GD, Bayless TM, Baylin SB (1980) Diamine oxidase (DAO) a circulating marker for rat mucosal maturation and integrity. J Clin Invest 66:66–70

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Nakao M, Ogura Y, Satake S, Ito I, Iguchi A, Takagi K, Nabeshima T (2002) Usefulness of soluble dietary fiber for the treatment of diarrhea during enteral nutrition in elderly patients. Nutrition 18:35–39

    Article  PubMed  Google Scholar 

  10. Anderson JW, Baird P, Davis RH Jr, Ferreri S, Knudtson M, Koraym A, Waters V, Williams CL (2009) Health benefits of dietary fiber. Nutr Rev 67:188–205

    Article  PubMed  Google Scholar 

  11. Dranitsaris G, Shah A, Spirovski B, Vincent M (2007) Severe diarrhea in patients with advanced-stage colorectal cancer receiving FOLFOX or FOLFIRI chemotherapy: the development of a risk prediction tool. Clin Colorectal Cancer 6:367–373

    Article  CAS  PubMed  Google Scholar 

  12. Stein A, Voigt W, Jordan K (2010) Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management. Ther Adv Med Oncol 2:51–63

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Moriyama K, Kouchi Y, Morinaga H, Irimura K, Hayashi T, Ohuchida A, Goto T, Yoshizawa Y (2006) Diamine oxidase, a plasma biomarker in rats to GI tract toxicity of oral fluorouracil anti-cancer drugs. Toxicology 217:233–239

    Article  CAS  PubMed  Google Scholar 

  14. Siber GR, Mayer RJ, Levin MJ (1980) Increased gastrointestinal absorption of large molecules in patients after 5-fluorouracil therapy for metastatic colon carcinoma. Cancer Res 40:3430–3436

    CAS  PubMed  Google Scholar 

  15. Kusche J, Mennigen R, Erpenbach K (1988) The intestinal diamine oxidase activity under the influence of adaptive proliferation of intestinal mucosa—a proliferation terminating principle? Agents Actions 23:354–356

    Article  CAS  PubMed  Google Scholar 

  16. Fukunaga T, Sasaki M, Araki Y, Okamoto T, Yasuoka T, Tsujikawa T, Fujiyama Y, Bamba T (2003) Effects of the soluble fibre pectin on intestinal cell proliferation, fecal short chain fatty acid production and microbial population. Digestion 67:42–49

    Article  CAS  PubMed  Google Scholar 

  17. Tappenden KA, Albin DM, Bartholome AL, Mangian HF (2003) Glucagon-like peptide-2 and short-chain fatty acids: a new twist to an old story. J Nutr 133:3717–3720

    CAS  PubMed  Google Scholar 

  18. Gee JM, Lee-Finglas W, Wortley GW, Johnson IT (1996) Fermentable carbohydrates elevate plasma enteroglucagon but high viscosity is also necessary to stimulate small bowel mucosal cell proliferation in rats. J Nutr 126:373–379

    CAS  PubMed  Google Scholar 

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Acknowledgments

Part of this study was reported at a workshop during the 43th annual meeting of the Japanese Society for Clinical Molecular Morphology and in a symposium presented to the 44th annual meeting of the Japanese Society for Clinical Molecular Morphology. We are grateful to Mr. Kenichi Yagyuu and Ms. Yuka Takezaki for their excellent technical assistance. This work was supported by a Grant in Aid for Scientific Research (22501045).

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Correspondence to Michiya Kobayashi.

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Fukudome, I., Kobayashi, M., Dabanaka, K. et al. Diamine oxidase as a marker of intestinal mucosal injury and the effect of soluble dietary fiber on gastrointestinal tract toxicity after intravenous 5-fluorouracil treatment in rats. Med Mol Morphol 47, 100–107 (2014). https://doi.org/10.1007/s00795-013-0055-7

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  • DOI: https://doi.org/10.1007/s00795-013-0055-7

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