Effects of intervention with sulindac and inulin/VSL#3 on mucosal and luminal factors in the pouch of patients with familial adenomatous polyposis

Int J Colorectal Dis. 2011 May;26(5):575-82. doi: 10.1007/s00384-010-1127-y. Epub 2011 Jan 18.

Abstract

Background/aim: In order to define future chemoprevention strategies for adenomas or carcinomas in the pouch of patients with familial adenomatous polyposis (FAP), a 4-weeks intervention with (1) sulindac, (2) inulin/VSL#3, and (3) sulindac/inulin/VSL#3 was performed on 17 patients with FAP in a single center intervention study. Primary endpoints were the risk parameters cell proliferation and glutathione S-transferase (GST) detoxification capacity in the pouch mucosa; secondary endpoints were the short chain fatty acid (SCFA) contents, pH, and cytotoxicity of fecal water.

Methods: Before the start and at the end of each 4-week intervention period, six biopsies of the pouch were taken and feces was collected during 24 h. Cell proliferation and GST enzyme activity was assessed in the biopsies and pH, SCFA contents, and cytotoxicity were assessed in the fecal water fraction. The three interventions (sulindac, inulin/VSL#3, sulindac/inulin/VSL#3) were compared with the Mann-Whitney U test.

Results: Cell proliferation was lower after sulindac or VSL#3/inulin, the combination treatment with sulindac/inulin/VSL#3 showed the opposite. GST enzyme activity was increased after sulindac or VSL#3/inulin, the combination treatment showed the opposite effect. However, no significance was reached in all these measures. Cytotoxicity, pH, and SCFA content of fecal water showed no differences at all among the three treatment groups.

Conclusion: Our study revealed non-significant decreased cell proliferation and increased detoxification capacity after treatment with sulindac or VSL#3/inulin; however, combining both regimens did not show an additional effect.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / drug therapy*
  • Adenomatous Polyposis Coli / pathology
  • Adult
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cell Death / drug effects
  • Cell Proliferation / drug effects
  • Colonic Pouches / pathology*
  • Endpoint Determination
  • Fatty Acids / metabolism
  • Feces
  • Female
  • Glutathione Transferase / metabolism
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology*
  • Inulin / pharmacology
  • Inulin / therapeutic use*
  • Male
  • Middle Aged
  • Probiotics / therapeutic use*
  • Sulindac / administration & dosage
  • Sulindac / pharmacology
  • Sulindac / therapeutic use*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Fatty Acids
  • Sulindac
  • Inulin
  • Glutathione Transferase