Submitted to: Xenobiotica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/30/2002
Publication Date: 2/15/2003
Citation: ROWLANDS, J.C., HE, L., BADGER, T.M. Glucose influences the induction of CYP2E1 mRNA expression by ethanol in FGC-4 cells. XENOBIOTICA. 2003. v. 33. p. 283-287. Interpretive Summary: The effects of dietary factors or drugs are can be influenced by other components of the diet. We have been studying the role of carbohydrates in the health effects of alcohol. Our previous studies have suggested that alcohol can have damaging effects to the liver if the carbohydrate levels in the diet are low. The current study was conducted to determine the mechanism by which that might occur. We used liver cells that were cultured in the presence or absence of carbohydrate and then exposed them to alcohol. The alcohol increased the production of an enzyme, CYP2E1, in cells not treated with carbohydrate, but there was no CYP2E1 increase when Carbohydrates were present. Since CYP2E1 is known to increase free radical formation and result in damage, these results suggest that carbohydrates may be protective against at least of the tissue damaging effects of alcohol that could lead to alcohol-induced liver disease.
Technical Abstract: Rats fed intragastrically with ethanol-containing diets made with low levels of carbohydrates (CHO) have greater CYP2E1 induction than rats fed similar diets made with high CHO levels. In this study, FGC-4 rat hepatoma cells were used to test the hypothesis that CHO could down regulate ethanol-induced CYP2E induction. 3. FGC-4 cells grown in a glucose-free media and treated with 1-100 mM ethanol for 24 h exhibited a dose-dependent increase (p<0.05) in CYP2E1, with maximum mRNA steady-state (3.8 fold) or protein (3.1 fold) levels measured at 30 mM or 100 mM ethanol, respectively. In cells treated with 30 mM ethanol, a glucose concentration-dependent inhibition (p<0.05) of CYP2E1 mRNA was observed between 2.5 and 10 mM glucose. Induction by 30 mM ethanol of CYP2E1 protein was reduced in cells co-treated with 1 mM or greater glucose and complete inhibition was measured with 5 mM glucose co-treatment. These data demonstrate that under culture conditions of extremely low CHO concentrations: a) ethanol treatment of FGC-4 cells results in elevated steady-state levels of CYP2E1 mRNA and protein; and b) glucose inhibits this increase. We conclude that glucose can negatively regulate CYP2E1 expression and could at least partially explain the greater induction of hepatic CYP2E1in rats fed low CHO ethanol-containing diets compared with high CHO diets at the same ethanol level.