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Alcohol and Alcoholism Vol. 37, No. 4, pp. 322-326, 2002
© 2002 Medical Council on Alcohol

MICROBES AND MUCOSA IN THE REGULATION OF INTRACOLONIC ACETALDEHYDE CONCENTRATION DURING ETHANOL CHALLENGE

Jukka-Pekka Visapää, Jyrki Tillonen and Mikko Salaspuro,*

Research Unit of Substance Abuse Medicine, Biomedicum Helsinki, PL 700, 00029 HUS, Finland

Received 27 July 2001; in revised form 18 January 2002; accepted 7 February 2002

— Aims: 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 KM 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.


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