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


CONCLUSIONS
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.
Department of Gastroenterology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Pieter
P
Friederich
Jelle
J
Verschuur
Bjorn W H
BW
van Heumen
Hennie M J
HM
Roelofs
Marloes
M
Berkhout
Iris D
ID
Nagtegaal
Martijn G H
MG
van Oijen
Johannes H J M
JH
van Krieken
Wilbert H M
WH
Peters
Fokko M
FM
Nagengast
D011125:Adenomatous Polyposis Coli / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D039021:Colonic Pouches / Q000473:pathology*; D023381:Endpoint Determination; D005227:Fatty Acids / Q000378:metabolism; D005243:Feces; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D007444:Inulin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019936:Probiotics / Q000627:therapeutic use*; D013467:Sulindac / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
D000970:Antineoplastic Agents; D005227:Fatty Acids; D013467:Sulindac; D007444:Inulin; D005982:Glutathione Transferase
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