Deoxycholate inhibits in vivo butyrate-mediated BrDU labeling of the colonic crypt.
The short-chain fatty acid butyrate (NaBu) selectively increases colonic crypt base proliferation and inhibits "premalignant" crypt surface hyperproliferation while the secondary bile acid deoxycholate (DCA) induces surface hyperproliferation, in vitro. We hypothesized that NaBu and DCA have similar selective and antagonistic effects on the colonic crypt proliferative pattern, in vivo. Fifty-six adult SD rats underwent surgical isolation of the colon and 24-hr intraluminal instillation with physiological (10 mM) and pharmacological (25 mM) levels of butyrate alone or combined with a physiological DCA level (5 microM). Bromodeoxyuridine-labeling indices (LI) were determined as labeled cells divided by total cells, for the whole crypt and five crypt compartments from base to surface. Treatment with NaBu increased total LI when compared to NaCl. This effect was significant only at the crypt base. Both doses of NaBu resulted in similar LI with no further response at the higher concentration. In contrast to prior in vitro studies, DCA alone at this concentration did not affect LI, but when combined with NaBu, DCA inhibited the effects of NaBu at the crypt base and surface. The conclusions are: (1) the in vivo proliferative effects of NaBu are selective to the crypt base, (2) an in vivo low physiological DCA level does not promote crypt surface hyperproliferation but does inhibit butyrate's proliferative effect, and (3) NaBu and DCA interact in a complex and antagonistic manner to selectively modulate crypt base and surface proliferation, in the rat colon, in vivo. These findings may have clinical relevance since colonic levels of NaBu and DCA are affected by diet.
Velázquez
O C
OC
Harrison Department of Surgical Research, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Seto
R W
RW
Bain
A M
AM
Fisher
J
J
Rombeau
J L
JL
D000818:Animals; D001973:Bromodeoxyuridine; D002087:Butyrates / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects*; D003106:Colon / Q000033:anatomy & histology / Q000166:cytology*; D003840:Deoxycholic Acid / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D002087:Butyrates; D003840:Deoxycholic Acid; D001973:Bromodeoxyuridine