Microbes and mucosa in the regulation of intracolonic acetaldehyde concentration during ethanol challenge.
OBJECTIVE
The bacteriocolonic pathway for ethanol oxidation leads to high intracolonic levels of carcinogenic acetaldehyde. The respective roles of colonic mucosal cells and gut flora in the regulation of intracolonic acetaldehyde concentration are not known. Disulfiram inhibits hepatic acetaldehyde oxidation and may have an effect on colonic mucosal cells. On the other hand, metronidazole treatment leads to overgrowth of acetaldehyde-producing aerobic flora in the large intestine. The aim of this study was to characterize by means of disulfiram and metronidazole the contribution of colonic mucosal cells and intracolonic microbes to the regulation of intracolonic acetaldehyde concentration during ethanol oxidation in rats.


METHODS
Forty male Wistar rats were used. Three groups of 10 rats each received metronidazole, disulfiram, or both for 5 days, and a fourth group of 10 rats served as controls and did not receive any premedication. Faecal samples were taken for the ALDH (aldehyde dehydrogenase) determination before the injection of ethanol, after which all rats received ethanol (1.5 g/kg) 2 h prior to taking samples from blood, liver, colonic mucosa and colonic contents.


RESULTS
Disulfiram decreased significantly hepatic and colonic mucosal ALDH activities, and resulted in increased blood and intracolonic acetaldehyde levels. In disulfiram-treated rats, mean intracolonic acetaldehyde level was 8-fold higher than that in the blood. Metronidazole inhibited only colonic mucosal high K(M) ALDH and increased intracolonic, but not blood, acetaldehyde levels. Faecal ALDH activity was not detectable in any of the groups.


CONCLUSIONS
This study demonstrates that during ethanol challenge, intracolonic acetaldehyde level is regulated not only by intracolonic microbes, but also by colonic mucosal cells.
Visapää
Jukka-Pekka
JP
Research Unit of Substance Abuse Medicine, Biomedicum Helsinki, PL 700, 00029 HUS, Finland.
Tillonen
Jyrki
J
Salaspuro
Mikko
M
D000079:Acetaldehyde / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001420:Bacteria, Aerobic; D003106:Colon / Q000382:microbiology*; D000431:Ethanol / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000382:microbiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; D000079:Acetaldehyde