|Badeaux, Jamie - ACNC|
|Hardy, Holly - ACNC|
|Floyd, Nellie - ACNC|
|Fletcher, Terry - UAMS|
|Ferguson, Matt - ACNC|
|Hale, Kim - ACNC|
|Dallari, Tammi - ACNC|
Submitted to: Society of Toxicology
Publication Type: Abstract Only
Publication Acceptance Date: September 30, 2002
Publication Date: March 9, 2003
Citation: BADEAUX, J., HARDY, H., FLOYD, N., FLETCHER, T., FERGUSON, M., HALE, K., DALLARI, T., RONIS, M., BADGER, T.M. EFFECTS OF LIGHT AND DARK BEERS ON HEPATIC CYTOCHROME P450 EXPRESSION IN MALE RATS RECIEVING ALCOHOLIC BEVERAGES AS PART OF TOTAL ENTERAL NUTRITION. SOCIETY OF TOXICOLOGY. 2003. v. 72. Abstract p. 110. Interpretive Summary: Drinking has long been known to alter the metabolism of drugs and cancer causing chemicals in the liver. Animal studies, confirmed in humans, have shown that alcohol consumption increases expression and activity of a liver enzyme known as CYP2E1 which is involved in metabolism of ethanol, many solvents and nitrosamine carcinogens. However, people do not drink pure ethanol. They drink alcoholic beverages such as beer and wine. These beverages contain many other chemicals (so-called cogeners) in addition to ethanol which may also have effects on drug metabolism. Virtually all animal studies of alcohol on drug metabolism use pure ethanol and might miss effects associated with consumption of all the other things in alcoholic drinks. In the current study, we fed rats two different beers: a larger and a stout and examined effects on liver drug metabolism by cytochrome P450-dependent monooxygenase enzymes. Compared to controls fed the same amount of pure ethanol, CYP2E1 levels were the same. However, stout fed-rats expressed more CYP1A2, CYP3A and CYP4A enzymes in their livers and had higher rates of metabolism of the antibiotic erythromycin. Therefore stout contains chemicals other than ethanol which also increase expression of some drug metabolizing enzymes in the liver.
Technical Abstract: Alcoholic beverages contain many congeners in addition to ethanol. Therefore, consumption of alcoholic beverages may have considerably different effects on expression of hepatic microsomal monooxygenases than the relatively selective induction of CYP2E1 observed following ethanol consumption. In the current study we compared the effects of two beers: larger (a light roasted beer) and stout (a dark roasted beer) infused intragastrically into groups of N = 10-13, 300 g male Sprague-Dawley rats for 21 d using a system of total enteral nutrition (TEN) with a group of rats infused an equivalent amount of ethanol isocalorically. At the end of the infusion period, rats were sacrificed and liver microsomes prepared. Cytochrome P450s CYP1A1/2, CYP2B1, CYP2E1, CYP3A and CYP4A expression was assessed by Western immunoblot analysis. In addition monooxygenase activities were assayed for the following substrates: ethoxy-, methoxy-, pentoxy- and benzyloxyresorufin, tesosterone, midazolam, erythromycin and p-nitrophenol. No effects of larger or stout were observed on relative expression of CYP2E1or CYP2B1 or activity towards p-nitrophenol or pentoxyresorufin. However, higher expression of CYP1A2, CYP3A and CYP4A were observed in stout-infused relative to larger and ethanol-infused rats (p less than/equal to 0.05). In addition, although no differences were observed in alkoxyresorufin, midazolam or testosterone metabolism between groups, stout-infused rat had greater erythromycin N-demethylase activity (a CYP3A substrate) and higher lauric acid 12-hydroxylase activity (a CYP4A substrate) than other groups (p 0.05). Therefore stout contains congeners which are inducers of cytochrome P450s other than CYP2E1.