Metronidazole increases intracolonic but not peripheral blood acetaldehydein chronic ethanol-treated rats

Background: Metronidazole leads to the over-growth of aerobic nora in the l arge intestine by reducing the number of anaerobes. According to our previo us studies, this shift may increase intracolonic bacterial acetaldehyde for mation if ethanol is present. Metronidazole is also reported to cause disul firam-like effects after alcohol intake, although the mechanism behind this is obscure. Therefore, the aim was to study the effect of long-term metron idazole and alcohol treatment on intracolonic acetaldehyde levels and to ex plore the possible role of intestinal bacteria in the metronidazole related disulfiram-like reaction. Methods: A total of 32 rats were divided into four groups: controls (n = 6) , controls receiving metronidazole (n = 6), ethanol group (II = 10), and et hanol and metronidazole group (n = 10). All rats were pair-fed with the liq uid diet for 6-weeks, whereafter blood and intracolonic acetaldehyde levels and liver and colonic mucosal alcohol (ADH) and aldehyde dehydrogenase (AL DH) activities were analyzed. Results: The rats receiving ethanol and metronidazole had five times higher intracolonic acetaldehyde: levels than the rats receiving only ethanol (43 1.4 +/ 1635 mu M vs. 84.7 +/- 14.4 mu M, p = 0.0035). In contrast, blood ac etaldehyde levels were equal. Cecal cultures showed the increased growth of Enterobacteriaceae in the metronidazole groups, Metronidazole had no inhib itory effect on hepatic or colonic mucosal ADH and ALDH activities. Conclusions: The increase in intracolonic acetaldehyde after metronidazole treatment is probably due to the replacement of intestinal anaerobes by ADH -containing aerobes. Unlike disulfiram, metronidazole neither inhibits Live r ALDH nor increases blood acetaldehyde. Thus, our findings suggested that the mechanism behind metronidazole related disulfiram-like reaction might b e located in the gut nora instead of the liver.