TY - JOUR T1 - Lack of Cytochrome P450 2E1 (CYP2E1) Induction in the Rat Liver by Starvation without Coprophagy JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 213 LP - 216 VL - 29 IS - 3 AU - Hye Chin Chung AU - Sang Hyun Sung AU - Jin Soo Kim AU - Young Choong Kim AU - Sang Geon Kim Y1 - 2001/03/01 UR - http://dmd.aspetjournals.org/content/29/3/213.abstract N2 - Starvation potentiates the hepatotoxicity of a variety of small molecules, including chlorinated hydrocarbons and nitrosamines, through the induction of CYP2E1. A change in CYP2E1 expression during starvation may also alter the pharmacokinetic profiles of xenobiotics. Northern blot and Western blot analyses revealed that hepatic CYP2E1 was not induced during starvation in rats placed in metabolic or wire-bottom cages in contrast to the induction of CYP2E1 in animals housed in solid-bottom cages. We studied the effect of coprophagy on the expression of hepatic CYP2E1 during starvation. The extent of coprophagy was 24% in fed rats. Fecal matter of starving rats was reduced to 14% of control and starving rats re-ingested ∼1.6 g of feces per day. The effect of fecal matter on CYP2E1 expression (i.e., 1.6 g/kg/day for 3 days) was assessed in fed or starving rats. Starving rats gavaged with fecal matter for 3 days resulted in a 3.5-fold increase in the level of CYP2E1 mRNA, while fed rats gavaged with feces failed to show an increase in the mRNA. The increase in the CYP2E1 mRNA level accompanied the induction of CYP2E1. Starving rats gavaged with methanol extract of feces (500 mg/kg/day for 3 days) showed a 3.3-fold increase in CYP2E1 mRNA level in the liver. These results provide evidence that CYP2E1 is not induced by starvation without coprophagy, raising the contention that the mechanistic basis for CYP2E1 induction by starvation should be reevaluated. The American Society for Pharmacology and Experimental Therapeutics ER -