Inhibition of intracolonic acetaldehyde production and alcoholic fermentation in rats by ciprofloxacin.
Heavy drinking is associated with many gastrointestinal symptoms and diseases, such as rapid intestinal transit time, diarrhea, colon polyps, and colorectal cancer. Acetaldehyde produced from ethanol by intestinal microbes has recently been suggested to be one of the pathogenetic factors related to alcohol-associated gastrointestinal morbidity. Furthermore, acetaldehyde is absorbed from the colon into portal blood and may thus contribute to the development of alcoholic liver injury. The present study was aimed to investigate the significance of gut aerobic flora in intracolonic acetaldehyde formation. For this study, 58 male Wistar rats (aged 9 to 11 weeks) were used. Half of the rats received ciprofloxacin for four consecutive days. Control rats (n = 29) received standard chow. On the fifth day of treatment, 1.5 g/kg body weight of ethanol was administered intraperitoneally to 19 rats receiving ciprofloxacin and 19 control rats. Ten ciprofloxacin-treated and 10 control rats received equal volumes of physiological saline intraperitoneally. Two hours after the injection of ethanol or saline, the samples of colonic contents and blood were obtained. Acetaldehyde and ethanol levels of the samples were determined by headspace gas chromatography. The intracolonic acetaldehyde level 2 hr after ethanol administration was 483+/-169 microM (maximum: 2.7 mM). High intracolonic acetaldehyde after ethanol injection was significantly reduced by ciprofloxacin treatment. After ciprofloxacin, intracolonic acetaldehyde levels before and after the injection of ethanol were 25+/-4.8 and 23+/-15 microM, respectively. Ciprofloxacin treatment resulted also in significantly higher blood (p < 0.005) and intracolonic (p < 0.0001) ethanol levels than in the control animals. Furthermore, ciprofloxacin treatment totally abolished the formation of endogenous ethanol in the large intestine. This study demonstrates that alcoholic fermentation and intracoIonic acetaldehyde production can be blocked by diminishing the amount of intracolonic aerobic bacteria with ciprofloxacin. Our findings indicate that the bacteriocolonic pathway for ethanol oxidation is mediated almost exclusively by gut aerobic microbes, and this knowledge may provide new insights into the studies on the pathogenesis of alcohol-related gastrointestinal symptoms and diseases.
Visapää
J P
JP
Research Unit of Alcohol Diseases, Helsinki University Central Hospital, Finland.
Jokelainen
K
K
Nosova
T
T
Salaspuro
M
M
D000079:Acetaldehyde / Q000493:pharmacokinetics*; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001420:Bacteria, Aerobic / Q000187:drug effects* / Q000201:enzymology; D002939:Ciprofloxacin / Q000494:pharmacology*; D003106:Colon / Q000382:microbiology*; D000431:Ethanol / Q000493:pharmacokinetics*; D005285:Fermentation / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D000431:Ethanol; D002939:Ciprofloxacin; D000426:Alcohol Dehydrogenase; D000079:Acetaldehyde