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Effects of the coffee constituents cafestol and kahweol on the expression of xenobiotic metabolising enzymes in the rat liver
Book of Abstracts- EUROTOX ‘94
75
mineral particles may stimulate nitric oxide (NOI synthase and thereby induce the production of NO. NO may pfay a role in fibre-induced cellular signailing, and as a highly toxic radial it may ampli~c~okine-, such as interferon-gamma, induced cytotoxicity. Sunpotted by the Finnish Work Environment Fund and The Academy of Finland. Key words: mineral particles; phagocytes; inositol phosphates; calcium
ToxfcofogfcalRehabMtatfonof AbsfnthfumLfqueur I. Schaefer. E Bindlet ’ , A. Luanier. faboratoire de Toxicologic Fondamental% et du M~dicament, Strasbourg, France; 1 ~~~toif% de #~mie Ana~que, Facuft& de Pbarmacie, ~o~e~~~ Louis F&teu& S~bourg~ l+nc% The absinthium liqueur (“absinthe”) was very popular in the last century, especially in Switzerland and in France. As it contained the essential oil absinthol and particularly a convulsant substance (thujone). the liqueur was the subject of intensive scientific and social polemics that lead for toxicological reasons (absinthism) to its interdiction in the different countries (Swi~erland: July5th, 1908; France: March 16th. 1915f. We have reinvestigated thii question by analyzing the principal substances of absinthol and associated essential oils (anise, star anise, fennel) encountered in absinthium alcoholic beverages. A capillary gas chromatography method was specially developed. The study has concerned the analyzes of a legal french liqueur dating of 1904, three actual legal Spanish absinthes, a recent fraudulent swiss liqueur and a french iflegal alcoholic maceration of the plant ~e~~;~ ~s~n~~urn). The percent volume of ethanol was comprised between 46-500/o, except for the old french liquor @#%I. ‘ihujone concentretions were very low (4.7-6.2 rg/lr. Also, it appears that thujone cannot be related to toxic events in absinthium liqueurs and thus “absinthe” could be rehabilitate. Key words: absinthium; alcohol; thujone; anethole; gas chromatography;
liqueur
Effectsof tha Coffee ConstituentsCafestofand Kahwaofon the Expreasfonof Xenobfotfc ~~ffsf~ EnzymesIn the f?atLfver 8. Schilter, A. Huggett. Department of&&y Vers-chez-/es-8lanc. Lausanne, Switzerland
and SafetyAssurance, Nesfec Ltd Research Centre,
The coffee-specific diterpenes cafestol and kahweot (C + K), which comprise up to about 10-l5% of the lipid fraotion of roasted coffee beans, have recentfy been shown to possess several important biolog;cal activities. For example they modulate serum cholesterol levels and they have been reported to have anticarcinogenic properties. The latter activity may be related to their ability to induce glutathione S-transferase (GST). However, little is known concerning their effects on other xenobiotic metabolising and detoxifying systems. In a subthronic feeding study we examined the influence of a mixture of C c K on the expression of various enzymes involved in xenobiotic metabolism. Anafysis focused on liver samples from rats fed a mixture of C + K incorporated at four dose levels (92,420.2300.6200 ppm) in the diet for 28 or 91 days. The expression of mRNAs specific for cytochromes P45Os CYPtAl, CYPlA2, CYP261, CYP282 and CYP3Al as well as for GST alpha sub-units Yal , Ya2, Yc and the GST mu subunits Yb‘r and Yb2 were assayed. For this purpose ht@tly selective synthetic oligomen capable of discrjmi~ting between naturally related gene products were employed. C + K induced a dose-dependent increase in the expression of mRNAs encoding the P45Os CYP281, CYP2B2 and CYP3Al. The effects of C + K on the expression of liver GST was subunitdependent. Compared to control animals, the content of mRNAs encoding GST subunit Yal was unaffected, Yb2 and Yc were increased slightly and Ybl was markedly increased, consistent with an overall induction of the GST mu form. We are currently investigating whether these findings reflect alterations at the level of enzymatic activity by employing specific substrates for different forms of P45Os and GSTs. Finally these observations will be correlated with other biological effects of these dietary constituents. Key words: cafestol; kahweol: P450: GST; rat
Delayed DevelopmentalImmune and Neurotoxfcftyof Benzodfazepfnea
r,
M. Schlumnf,f,A Schreiber, HR. Ramseier R. Parmar, A.R. Salili. H. van Loveren*. W. L~htenste~ge~ : /abbe Pharmacology and fnstitute of Exp&mental Immunofogy, University of Ztirich, ZLirch, Switlerfand; 2 Section of lmmunotoxicology! National institute of FWic Health and Environmental Rotection, Bilthoven, l?te Netherlands
of
Benzodiazepines (8DZ) are used in pregnancy in medical context or as misuse, even If recent epidemiologic and ex~rimental research signalizes harm to the unborn. 8DZ are ligands to the central GA8AA receptor present in the fetal brain. In the rat, prenatal !owdose exposure to 8DZ induces changes in G.A8AA receptor subunit mRNA expression which may represent neurochemical correlates to behavioral disturbances observed in the progeny of BDZ-treated dams. EDZ are also ligands with variable affinities to the peripheral type BDZ receptor (p8Ri. This
75
mineral particles may stimulate nitric oxide (NOI synthase and thereby induce the production of NO. NO may pfay a role in fibre-induced cellular signailing, and as a highly toxic radial it may ampli~c~okine-, such as interferon-gamma, induced cytotoxicity. Sunpotted by the Finnish Work Environment Fund and The Academy of Finland. Key words: mineral particles; phagocytes; inositol phosphates; calcium
ToxfcofogfcalRehabMtatfonof AbsfnthfumLfqueur I. Schaefer. E Bindlet ’ , A. Luanier. faboratoire de Toxicologic Fondamental% et du M~dicament, Strasbourg, France; 1 ~~~toif% de #~mie Ana~que, Facuft& de Pbarmacie, ~o~e~~~ Louis F&teu& S~bourg~ l+nc% The absinthium liqueur (“absinthe”) was very popular in the last century, especially in Switzerland and in France. As it contained the essential oil absinthol and particularly a convulsant substance (thujone). the liqueur was the subject of intensive scientific and social polemics that lead for toxicological reasons (absinthism) to its interdiction in the different countries (Swi~erland: July5th, 1908; France: March 16th. 1915f. We have reinvestigated thii question by analyzing the principal substances of absinthol and associated essential oils (anise, star anise, fennel) encountered in absinthium alcoholic beverages. A capillary gas chromatography method was specially developed. The study has concerned the analyzes of a legal french liqueur dating of 1904, three actual legal Spanish absinthes, a recent fraudulent swiss liqueur and a french iflegal alcoholic maceration of the plant ~e~~;~ ~s~n~~urn). The percent volume of ethanol was comprised between 46-500/o, except for the old french liquor @#%I. ‘ihujone concentretions were very low (4.7-6.2 rg/lr. Also, it appears that thujone cannot be related to toxic events in absinthium liqueurs and thus “absinthe” could be rehabilitate. Key words: absinthium; alcohol; thujone; anethole; gas chromatography;
liqueur
Effectsof tha Coffee ConstituentsCafestofand Kahwaofon the Expreasfonof Xenobfotfc ~~ffsf~ EnzymesIn the f?atLfver 8. Schilter, A. Huggett. Department of&&y Vers-chez-/es-8lanc. Lausanne, Switzerland
and SafetyAssurance, Nesfec Ltd Research Centre,
The coffee-specific diterpenes cafestol and kahweot (C + K), which comprise up to about 10-l5% of the lipid fraotion of roasted coffee beans, have recentfy been shown to possess several important biolog;cal activities. For example they modulate serum cholesterol levels and they have been reported to have anticarcinogenic properties. The latter activity may be related to their ability to induce glutathione S-transferase (GST). However, little is known concerning their effects on other xenobiotic metabolising and detoxifying systems. In a subthronic feeding study we examined the influence of a mixture of C c K on the expression of various enzymes involved in xenobiotic metabolism. Anafysis focused on liver samples from rats fed a mixture of C + K incorporated at four dose levels (92,420.2300.6200 ppm) in the diet for 28 or 91 days. The expression of mRNAs specific for cytochromes P45Os CYPtAl, CYPlA2, CYP261, CYP282 and CYP3Al as well as for GST alpha sub-units Yal , Ya2, Yc and the GST mu subunits Yb‘r and Yb2 were assayed. For this purpose ht@tly selective synthetic oligomen capable of discrjmi~ting between naturally related gene products were employed. C + K induced a dose-dependent increase in the expression of mRNAs encoding the P45Os CYP281, CYP2B2 and CYP3Al. The effects of C + K on the expression of liver GST was subunitdependent. Compared to control animals, the content of mRNAs encoding GST subunit Yal was unaffected, Yb2 and Yc were increased slightly and Ybl was markedly increased, consistent with an overall induction of the GST mu form. We are currently investigating whether these findings reflect alterations at the level of enzymatic activity by employing specific substrates for different forms of P45Os and GSTs. Finally these observations will be correlated with other biological effects of these dietary constituents. Key words: cafestol; kahweol: P450: GST; rat
Delayed DevelopmentalImmune and Neurotoxfcftyof Benzodfazepfnea
r,
M. Schlumnf,f,A Schreiber, HR. Ramseier R. Parmar, A.R. Salili. H. van Loveren*. W. L~htenste~ge~ : /abbe Pharmacology and fnstitute of Exp&mental Immunofogy, University of Ztirich, ZLirch, Switlerfand; 2 Section of lmmunotoxicology! National institute of FWic Health and Environmental Rotection, Bilthoven, l?te Netherlands
of
Benzodiazepines (8DZ) are used in pregnancy in medical context or as misuse, even If recent epidemiologic and ex~rimental research signalizes harm to the unborn. 8DZ are ligands to the central GA8AA receptor present in the fetal brain. In the rat, prenatal !owdose exposure to 8DZ induces changes in G.A8AA receptor subunit mRNA expression which may represent neurochemical correlates to behavioral disturbances observed in the progeny of BDZ-treated dams. EDZ are also ligands with variable affinities to the peripheral type BDZ receptor (p8Ri. This