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Cotinine effects on bile flow and biliary NNK elimination
H Meiser1, S E Atawodi, E Richter
1Walther Straub Institute of Pharmacology and Toxicology, Nussbaumstr. 26, D-80336 Munich, Germany.
European Journal of Medical Research
|July 7, 2000
Summary
Cotinine, a nicotine metabolite, was found to inhibit bile flow in rats. This reduces the elimination of tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), potentially increasing carcinogen levels.
Area of Science:
- Toxicology
- Pharmacokinetics
- Metabolism studies
Background:
- Nicotine and its metabolite cotinine are known to affect the metabolism of tobacco-specific nitrosamines like 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
- Previous research suggests that cotinine may influence alternative metabolic pathways for NNK, such as enhanced biliary excretion of NNAL-Gluc.
Purpose of the Study:
- To investigate the effect of cotinine on the biliary elimination of NNK and its metabolites in rats.
- To determine if cotinine influences bile flow and the excretion of NNK-derived compounds.
Main Methods:
- Rats with bile duct cannulation were administered [56sup;-3 H]-NNK intravenously.
- Cotinine or nicotine was co-administered to assess their impact on NNK biliary excretion.
- Bile flow and radioactivity in bile were measured over six hours.
Main Results:
- Cotinine significantly reduced cumulative bile flow by 42% and biliary elimination of NNK-derived radioactivity by 27% within six hours.
- Nicotine demonstrated a similar inhibitory effect on bile flow.
- The metabolic profile of NNK in bile remained unchanged despite cotinine administration.
Conclusions:
- This study provides the first experimental evidence that cotinine inhibits bile flow in rats.
- Reduced biliary elimination of NNK due to cotinine may increase the body's carcinogen burden.
- Inhibition of bile flow by tobacco alkaloids could contribute to the appetite-suppressing effects of tobacco products in humans.