Tillonen J, Väkeväinen S, Salaspuro V, Zhang Y, Rautio M, Jousimies-Somer H, Lindros K, Salaspuro M
Research Unit of Alcohol Diseases, Helsinki University Central Hospital, Finland.
Alcohol Clin Exp Res. 2000 Apr;24(4):570-5.
Metronidazole leads to the overgrowth of aerobic flora in the large intestine by reducing the number of anaerobes. According to our previous studies, this shift may increase intracolonic bacterial acetaldehyde formation if ethanol is present. Metronidazole is also reported to cause disulfiram-like effects after alcohol intake, although the mechanism behind this is obscure. Therefore, the aim was to study the effect of long-term metronidazole and alcohol treatment on intracolonic acetaldehyde levels and to explore the possible role of intestinal bacteria in the metronidazole related disulfiram-like reaction.
A total of 32 rats were divided into four groups: controls (n = 6), controls receiving metronidazole (n = 6), ethanol group (n = 10), and ethanol and metronidazole group (n = 10). All rats were pair-fed with the liquid diet for 6-weeks, whereafter blood and intracolonic acetaldehyde levels and liver and colonic mucosal alcohol (ADH) and aldehyde dehydrogenase (ALDH) activities were analyzed.
The rats receiving ethanol and metronidazole had five times higher intracolonic acetaldehyde levels than the rats receiving only ethanol (431.4 +/- 163.5 microM vs. 84.7 +/- 14.4 microM,p = 0.0035). In contrast, blood acetaldehyde levels were equal. Cecal cultures showed the increased growth of Enterobacteriaceae in the metronidazole groups. Metronidazole had no inhibitory effect on hepatic or colonic mucosal ADH and ALDH activities.
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 liver ALDH nor increases blood acetaldehyde. Thus, our findings suggested that the mechanism behind metronidazole related disulfiram-like reaction might be located in the gut flora instead of the liver.
甲硝唑通过减少厌氧菌数量导致大肠需氧菌群过度生长。根据我们之前的研究，如果存在乙醇，这种菌群变化可能会增加结肠内细菌乙醛的生成。也有报道称甲硝唑在摄入酒精后会引起双硫仑样反应，但其背后的机制尚不清楚。因此，本研究旨在探讨长期使用甲硝唑和酒精对结肠内乙醛水平的影响，并探究肠道细菌在甲硝唑相关双硫仑样反应中可能发挥的作用。
将32只大鼠分为四组：对照组（n = 6）、接受甲硝唑的对照组（n = 6）、乙醇组（n = 10）以及乙醇和甲硝唑组（n = 10）。所有大鼠均配对喂食液体饲料6周，之后分析血液和结肠内乙醛水平以及肝脏和结肠黏膜酒精脱氢酶（ADH）和乙醛脱氢酶（ALDH）活性。
接受乙醇和甲硝唑的大鼠结肠内乙醛水平比仅接受乙醇的大鼠高五倍（431.4±163.5微摩尔/升对84.7±14.4微摩尔/升，p = 0.0035）。相比之下，血液乙醛水平相当。盲肠培养显示甲硝唑组肠杆菌科细菌生长增加。甲硝唑对肝脏或结肠黏膜ADH和ALDH活性无抑制作用。
甲硝唑治疗后结肠内乙醛增加可能是由于含ADH的需氧菌取代了肠道厌氧菌。与双硫仑不同，甲硝唑既不抑制肝脏ALDH也不增加血液乙醛。因此，我们的研究结果表明，甲硝唑相关双硫仑样反应的机制可能位于肠道菌群而非肝脏。
