Microbes and mucosa in the regulation of intracolonic acetaldehyde concentration during ethanol challenge |
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Authors: | Visapää Jukka-Pekka Tillonen Jyrki Salaspuro Mikko |
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Institution: | Research Unit of Substance Abuse Medicine, Biomedicum Helsinki, PL 700, 00029 HUS, Finland |
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Abstract: | Aims: The bacteriocolonic pathway for ethanol oxidationleads to high intracolonic levels of carcinogenic acetaldehyde.The respective roles of colonic mucosal cells and gut florain the regulation of intracolonic acetaldehyde concentrationare not known. Disulfiram inhibits hepatic acetaldehyde oxidationand may have an effect on colonic mucosal cells. On the otherhand, metronidazole treatment leads to overgrowth of acetaldehyde-producingaerobic flora in the large intestine. The aim of this studywas to characterize by means of disulfiram and metronidazolethe contribution of colonic mucosal cells and intracolonic microbesto the regulation of intracolonic acetaldehyde concentrationduring ethanol oxidation in rats. Methods: Forty male Wistarrats were used. Three groups of 10 rats each received metronidazole,disulfiram, or both for 5 days, and a fourth group of 10 ratsserved as controls and did not receive any premedication. Faecalsamples were taken for the ALDH (aldehyde dehydrogenase) determinationbefore the injection of ethanol, after which all rats receivedethanol (1.5 g/kg) 2 h prior to taking samples from blood, liver,colonic mucosa and colonic contents. Results: Disulfiram decreasedsignificantly hepatic and colonic mucosal ALDH activities, andresulted in increased blood and intracolonic acetaldehyde levels.In disulfiram-treated rats, mean intracolonic acetaldehyde levelwas 8-fold higher than that in the blood. Metronidazole inhibitedonly colonic mucosal high KM ALDH and increased intracolonic,but not blood, acetaldehyde levels. Faecal ALDH activity wasnot detectable in any of the groups. Conclusions: This studydemonstrates that during ethanol challenge, intracolonic acetaldehydelevel is regulated not only by intracolonic microbes, but alsoby colonic mucosal cells. |
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