Demonstration of a direct stimulatory effect of bile salts on rat colonic epithelial cell proliferation.
BACKGROUND
Despite the clear demonstration that an increase in faecal bile salt concentration can augment colonocyte proliferation, it is still controversial whether bile salts act on these cells as direct mitogens or by inducing a damage-related proliferative response. The goal of this study was to define the mechanism mediating the proliferative effect of bile salts on rat colonocytes.


METHODS
Faecal bile salt concentration was increased by feeding rats on diets enriched with either bile salts or fats. Colonic mucosa proliferating cell nuclear antigen (PCNA) expression, histology and apoptosis, and faecal water cytolytic activity were evaluated to assess proliferation and direct or indirect signs of mucosal damage.


RESULTS
Compared to standard diet, chenodeoxycholate-, deoxycholate- and fat-enriched diets produced a significant increase in both faecal water total bile salt concentration (46.0 versus 124.1, 145.9 and 498.5 micromol/L, respectively) and percentage of PCNA-positive nuclei (30.5, versus 37.7, 33.9 and 47.1, respectively) that appeared significantly correlated (r = 0.8; P < 0.001). Chenodeoxycholate and deoxycholate fed animals showed colonic mucosa histology and faecal water cytolytic activity similar to controls, with a significantly reduced apoptotic index. Rats fed on high fat diet, however, showed a mild inflammatory infiltrate associated with an increased apoptosis and faecal water cytolytic activity, all conditions not apparently determined by the increased faecal water total bile salt concentration.


CONCLUSIONS
The results obtained in this study demonstrate that bile salts act as direct mitogens on colonic epithelial cells.
Barone
M
M
Dept of Emergency and Organ Transplantation, University of Bari, Italy. drbarone@yahoo.com
Berloco
P
P
Ladisa
R
R
Ierardi
E
E
Caruso
M L
ML
Valentini
A M
AM
Notarnicola
M
M
Di
Leo A
LA
Francavilla
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001647:Bile Acids and Salts / Q000032:analysis / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D003110:Colonic Neoplasms / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D012307:Risk Factors; D013268:Stimulation, Chemical
D001647:Bile Acids and Salts