Submitted to: Alcoholism: Clinical and Experimental
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/15/2005
Publication Date: 5/15/2005
Citation: Hidestrand, M., Shankar, K., Ronis, M.J., Badger, T.M. 2005. Effects of light and dark beers on hepatic cytochrome p450 expression in male rats receiving alcoholic beverages as part of total enteral nutrition. Alcoholism: Clinical and Experimental. 29(5):888-895.
Interpretive Summary: Consumption of beer represents a significant percentage of the total dietary calories in a relatively large number of Americans. While studies have suggested that moderate beer consumption (1 or 2 per day in women and males, respectively) is associated with improved health, the type of beer may be an important determinant of health consequences of beer. We studied light (lager) and dark (stout) beer to determine if biomarkers of adverse effects were more or less prevalent in dark beers. We found that there was greater expression of some metabolic proteins usually associated with intake of toxic compounds in animals fed dark beer as compared with light beer or pure ethanol, but in general those biomarkers associated with conditions like colon cancer did not differ between groups. These data suggest that at moderate beer intake, that is likely to be no differences in the health effects of light and dark beers.
Technical Abstract: Background: 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 consumption of pure ethanol. Methods: In the current study we compared the effects of two beers: lager (a light roasted beer) and stout (a dark roasted beer) infused intragastrically into 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 isocaloriclly. At the end of the infusion period, rats were sacrificed and liver and intestinal microsomes were prepared. Cytochromes P450 CYP1A1/2, CYP2B1, CYP3A and CYP4A expressions and activities were assessed by Western immunoblot and by using P450 enzyme specific substrates, respectively. Results: The relative expression of CYP2E1 and CYP2B1 and the activities towards p-nitrophenol; pentoxyresorufin or benzyloxyresorufin did not differ between beers. However, the expression of CYP1A2, CYP3A and CYP4A apoproteins was greater in liver microsomes from stout-infused relative to lager and ethanol-infused rats (P<0.05). In addition, although no significant differences were observed in EROD, MROD, midazolam or testosterone hydroxylase activities between groups, stout-infused rats had greater hepatic microsomal erythromycin N-demethylase activity (a CYP3A substrate) than other groups (P<0.05). Moreover, lauric acid 12-hydroxylase activity (a CYP4A substrate) was reduced (P<0.05) in microsomes from lager and stout fed-rats, but after oxidation with potassium ferricyanide this activity was significantly elevated in microsomes from only stout-fed animals. Conclusions: Therefore, stout contains components other than ethanol which interact in a complex fashion with the monooxygenase system. Key words: Total enteral nutrition, alcohol, beer, Cytochromes P450, enzyme-substrate complex