Medical Oncology

, Volume 27, Issue 3, pp 690–696 | Cite as

Intestinal permeability, vitamin A absorption, alpha-tocopherol, and neopterin in patients with rectal carcinoma treated with chemoradiation

  • Josef Dvořák
  • Bohuslav MelicharEmail author
  • Radomír Hyšpler
  • Lenka Krčmová
  • Lubor Urbánek
  • Hana Kalábová
  • Markéta Kašparová
  • Dagmar Solichová
Original Paper


Although gastrointestinal toxicity is one of the most common side effects of anticancer therapy, the diagnosis and assessment of this toxicity still depend mostly on anamnestic data. Measurement of intestinal permeability is one of potential methods of non-invasive laboratory evaluation of gastrointestinal toxicity. The aim of the present study was to investigate intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in patients with rectal carcinoma treated with chemoradiation. We have studied intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in 17 patients with rectal carcinoma treated with chemoradiation. Urinary lactulose, mannitol, and xylose were measured by capillary gas chromatography, and serum alpha-tocopherol, retinol, retinyl esters, and urinary neopterin were determined by high-performance liquid chromatography. Lactulose/mannitol ratio was increased 5 and 6 weeks after the start of the treatment. Serum alpha-tocopherol was decreased significantly throughout the course of treatment, but no significant changes were observed in postprandial serum concentrations of retinyl esters or in the concentrations of urinary neopterin. A correlation was observed between baseline parameters of intestinal permeability and urinary neopterin. The measurement of intestinal permeability using the lactulose/mannitol test may represent a sensitive tool in the detection of changes associated with chemoradiation in patients with rectal carcinoma. The therapy is also associated with a decrease of alpha-tocopherol.


Alpha-tocopherol 5-fluorouracil Intestinal permeability Neopterin Radiation Rectal carcinoma Retinyl esters 



This study was supported by the grant of the Internal Grant Agency of the Czech Republic NR9096-4 and Research Project MZO 00179906.


  1. 1.
    Sauer R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.CrossRefPubMedGoogle Scholar
  2. 2.
    Wolmark N, et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst. 2000;92:388–96.CrossRefPubMedGoogle Scholar
  3. 3.
    Melichar B, Dvorak J, Hyspler R, Zadak Z. Intestinal permeability in the assessment of intestinal toxicity of cytotoxic agents. Chemotherapy. 2005;51:336–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Bjarnason I, Macpherson A, Hollander D. Intestinal permeability: an overview. Gastroenterology. 1995;1995:1566–81.CrossRefGoogle Scholar
  5. 5.
    Uil JJ, et al. Clinical implications of the sugar absorption test: intestinal permeability test to assess mucosal barrier function. Scand J Gastroenterol. 1997;32:70–8.CrossRefGoogle Scholar
  6. 6.
    DeMeo MT, Mutlu EA, Keshavarzian A, Tobin MC. Intestinal permeation and gastrointestinal disease. J Clin Gastroenterol. 2002;34:385–96.CrossRefPubMedGoogle Scholar
  7. 7.
    Melichar B, et al. Intestinal permeability and vitamin A absoption in patients with chemotherapy-induced diarrhea. Am J Clin Oncol. 2008;31:580–4.CrossRefPubMedGoogle Scholar
  8. 8.
    Urbanek L, et al. Optimization and validation of a high performance liquid chromatography method for the simultaneous determination of vitamins A and E human serum using monolithic column and diode-array detection. Anal Chim Acta. 2006;573–574:267–72.CrossRefPubMedGoogle Scholar
  9. 9.
    Urbanek L, et al. Development and validation of a liquid chromatography method for the simultaneous determination of alpha-tocopherol, retinol and retinyl esters in human serum using a monolithic column for the monitoring of anticancer therapy side effects. J Sep Sci. 2006;29:2485–93.CrossRefPubMedGoogle Scholar
  10. 10.
    Borel P, et al. Processing of vitamin A and E in the human gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2001;280:G95–103.PubMedGoogle Scholar
  11. 11.
    Melichar B, et al. Urinary neopterin in patients with ovarian cancer. Pteridines. 2006;17:145–53.Google Scholar
  12. 12.
    Melichar B, Hyspler R, Kalabova H, Urbanek L, Krcmova L. Gastrointestinal permeability—a parameter of possible prognostic importance in metastatic colorectal carcinoma. Pteridines. 2008;19:19–22.Google Scholar
  13. 13.
    Melichar B, et al. Serum alpha-tocopherol, retinol and neopterin during paclitaxel/carboplatin chemotherapy. Anticancer Res. 2007;27:4397–401.PubMedGoogle Scholar
  14. 14.
    Cermanova M, et al. Urinary neopterin and microalbuminuria in patients treated by low-density lipoprotein apheresis. Pteridines. 2005;16:174–83.Google Scholar
  15. 15.
    Kohout P, Cerman J, Bratova M, Zadak Z. Small bowel permeability in patients with cytostatic therapy. Nutrition. 1999;15:546–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Daniele B, et al. Effect of chemotherapy with 5-fluorouracil on intestinal permeability and absorption in patients with advanced colorectal cancer. J Clin Gastroenterol. 2001;32:228–30.CrossRefPubMedGoogle Scholar
  17. 17.
    de la Maza MP, et al. Acute nutritional and intestinal changes after pelvic radiation. J Am Coll Nutr. 2001;20:637–42.Google Scholar
  18. 18.
    Vigneulle RM, Rao S, Fasano A, MacVittie TJ. Structural and functional alterations of the gastrointestinal tract following radiation-induced injury in the rhesus monkey. Digest Dis Sci. 2002;47:1480–91.CrossRefPubMedGoogle Scholar
  19. 19.
    Melichar B, et al. Intestinal permeability in patients with chemotherapy-induced stomatitis. J Cancer Res Clin Oncol. 2001;127:314–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Harrison EH, Hussain MM. Mechanisms involved in the intestinal digestion and absorption of dietary vitamin A. J Nutr. 2001;131:1405–8.PubMedGoogle Scholar
  21. 21.
    Johnson EJ, et al. Evaluation of vitamin A absorption by using oil-soluble and water-miscible vitamin A preparations in normal adults and in patients with gastrointestinal disease. Am J Clin Nutr. 1992;55:857–64.PubMedGoogle Scholar
  22. 22.
    Debier C, Larondelle Y. Vitamins A and E: metabolism, roles and transfer to offspring. Br J Nutr. 2005;93:153–74.CrossRefPubMedGoogle Scholar
  23. 23.
    McMillan DC, et al. The relationship between reduced vitamin antioxidant concentrations and the systemic inflammatory response in patients with common solid tumours. Clin Nutr. 2002;21:161–4.CrossRefPubMedGoogle Scholar
  24. 24.
    Mayland C, Allen KR, Degg TJ, Bennet M. Micronutrient concentrations in patients with malignant disease: effect of the inflammatory response. Ann Clin Biochem. 2004;41:138–41.CrossRefPubMedGoogle Scholar
  25. 25.
    McMillan DC, Sattar N, Talwar D, O’Reilly DS, McArdle CS. Changes in micronutrient concentrations following anti-inflammatory treatment in patients with gastrointestinal cancer. Nutrition. 2000;16:425–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Faure H, et al. 5-hydroxymethyluracil excretion, plasma TBARS and plasma antioxidant vitamins in adriamycin-treated patients. Free Rad Biol Med. 1996;20:979–83.CrossRefPubMedGoogle Scholar
  27. 27.
    Jonas RC, et al. Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients. Am J Clin Nutr. 2000;72:181–9.PubMedGoogle Scholar
  28. 28.
    High KP, et al. Low plasma concentrations of retinol and alpha-tocopherol in hematopoietic stem cell transplant recipients: the effect of mucositis and the risk of infection. Am J Clin Nutr. 2002;76:1358–66.PubMedGoogle Scholar
  29. 29.
    Faber M, Coudray C, Hida H, Mousseau M, Favier A. Lipid peroxidation products, and vitamin and trace element status in patients with cancer before and after chemotherapy, including adriamycin. A preliminary study. Biol Trace Elem Res. 1995;47:117–23.CrossRefPubMedGoogle Scholar
  30. 30.
    Kennedy DD, et al. Low antioxidant vitamin intakes are associated with increases in adverse effects of chemotherapy in children with acute lymphoblastic leukemia. Am J Clin Nutr. 2004;79:1029–36.PubMedGoogle Scholar
  31. 31.
    Delanian S, Porcher R, Balla-Mekias S, Lefaix JL. Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J Clin Oncol. 2003;21:2545–50.CrossRefPubMedGoogle Scholar
  32. 32.
    Pace A, et al. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. J Clin Oncol. 2003;21:927–31.CrossRefPubMedGoogle Scholar
  33. 33.
    Melichar B, Solichová D, Freedman RS. Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies. Int J Gynecol Cancer. 2006;16:240–52.CrossRefPubMedGoogle Scholar
  34. 34.
    Wachter H, Fuchs D, Hausen A, Reibnegger G, Werner ER. Neopterin as marker for activation of cellular immunity: immunologic basis and clinical application. Adv Clin Chem. 1989;27:81–141.CrossRefPubMedGoogle Scholar
  35. 35.
    Melichar B, et al. Urinary neopterin in patients with advanced colorectal carcinoma. Int J Biol Markers. 2006;21:190–8.PubMedGoogle Scholar
  36. 36.
    Tatzber F, et al. Elevated serum neopterin levels in atherosclerosis. Atherosclerosis. 1991;89:203–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Weiss G, et al. Increased concentrations of neopterin in carotid atherosclerosis. Atherosclerosis. 1994;106:263–71.CrossRefPubMedGoogle Scholar
  38. 38.
    Melicharova K, et al. Urinary neopterin in patients with diabetes mellitus and foot ulcers. Pteridines. 2007;18:128–31.Google Scholar
  39. 39.
    Melichar B, et al. Urinary neopterin, hemoglobin and peripheral blood cell counts in breast carcinoma patients treated with dose-dense chemotherapy. Anticancer Res. 2008;28:2389–96.PubMedGoogle Scholar
  40. 40.
    Reibnegger G, et al. Neopterin as a prognostic indicator in patients with carcinoma of the uterine cervix. Cancer Res. 1986;46:950–5.PubMedGoogle Scholar
  41. 41.
    Steinberg D. Oxidative modification of LDL and atherogenesis. Circulation. 1997;95:1062–71.PubMedGoogle Scholar
  42. 42.
    Keaney JF, et al. Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due to oxidized LDL by inhibiting protein kinase C stimulation. J Clin Invest. 1996;98:386–94.CrossRefPubMedGoogle Scholar
  43. 43.
    Salonen JT, et al. Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis. J Intern Med. 2000;248:377–86.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Josef Dvořák
    • 1
  • Bohuslav Melichar
    • 1
    • 4
    Email author
  • Radomír Hyšpler
    • 2
  • Lenka Krčmová
    • 2
    • 3
  • Lubor Urbánek
    • 2
    • 3
  • Hana Kalábová
    • 1
  • Markéta Kašparová
    • 2
    • 3
  • Dagmar Solichová
    • 2
  1. 1.Department of Oncology & RadiotherapyCharles University Medical School and Teaching HospitalHradec KrálovéCzech Republic
  2. 2.Department of Gerontology & Metabolic CareCharles University Medical School and Teaching HospitalHradec KrálovéCzech Republic
  3. 3.Department of Analytical ChemistryCharles University School of PharmacyHradec KrálovéCzech Republic
  4. 4.Department of OncologyPalacký University Medical School and Teaching HospitalOlomoucCzech Republic

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