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Rapid CommunicationShort Communication

Lack of Cytochrome P450 2E1 (CYP2E1) Induction in the Rat Liver by Starvation without Coprophagy

Hye Chin Chung, Sang Hyun Sung, Jin Soo Kim, Young Choong Kim and Sang Geon Kim
Drug Metabolism and Disposition March 2001, 29 (3) 213-216;
Hye Chin Chung
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Sang Hyun Sung
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Jin Soo Kim
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Young Choong Kim
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Sang Geon Kim
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Abstract

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.

Footnotes

  • Send reprint requests to: Sang Geon Kim, Ph.D., College of Pharmacy, Seoul National University, Sillim-dong, Kwanak-gu, Seoul 151-742, Korea. E-mail: sgk{at}snu.ac.kr

  • This work was supported by a Korea Research Foundation research fund and a research fund from Brain Korea 21.

  • Abbreviations used are::
    CYP
    cytochrome P450
    PNP
    p-nitrophenol
    SSC
    standard saline citrate
    • Received August 11, 2000.
    • Accepted November 13, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 29 (3)
Drug Metabolism and Disposition
Vol. 29, Issue 3
1 Mar 2001
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Rapid CommunicationShort Communication

Lack of Cytochrome P450 2E1 (CYP2E1) Induction in the Rat Liver by Starvation without Coprophagy

Hye Chin Chung, Sang Hyun Sung, Jin Soo Kim, Young Choong Kim and Sang Geon Kim
Drug Metabolism and Disposition March 1, 2001, 29 (3) 213-216;

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Rapid CommunicationShort Communication

Lack of Cytochrome P450 2E1 (CYP2E1) Induction in the Rat Liver by Starvation without Coprophagy

Hye Chin Chung, Sang Hyun Sung, Jin Soo Kim, Young Choong Kim and Sang Geon Kim
Drug Metabolism and Disposition March 1, 2001, 29 (3) 213-216;
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