Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors

Michio Morimoto, Ann Louise Hagbjork, Yu-Jui Yvonne Wan, Paul C. Fu, Paolo Clot, Emanuele Albano, Magnus Ingelman-Sundberg, Samuel W. French

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

This study was done to determine if a relationship exists between CYP2E1 induction by ethanol, lipid peroxidation, and liver pathology in experimental alcohol-induced liver disease in the rat. Rats were fed ethanol with or without diallyl sulfide (DAS) or phenethyl isothiocyanate (PIC) intragastrically for 1 month. CYP2E1 induction by ethanol was correlated with lipid peroxidation, liver microsomal CYP2E1 hydroxylation of paranitrophenol, and the liver pathology score using the data from the PIC-fed rats. Some of the data from the ethanol and DAS-fed rats were not included here because they have been reported elsewhere. Microsomal CYP2E1 protein levels induction by ethanol was decreased by PIC ingestion. Similarly, PIC reduced the increase microsomal reduced form of nicotinamide-adenine dinucleotide (NADPH)-dependent lipid peroxidation and p-nitrophenol hydroxylase (PNPH) activity, induced by ethanol feeding. The lipid peroxidation was reduced to below control levels; however, the pathology score was partially but not significantly reduced by isothiocyanate feeding. CYP2E1 messenger RNA (mRNA) was decreased by both inhibitors of CYP2E1. Immunohistochemical staining of liver for CYP2E1 protein showed that the lobular distribution of the isozyme changed from the centrilobular to a diffuse pattern, with an increase in the periportal region when the CYP2E1 inhibitors were fed with ethanol, and that this change correlated with the change in the distribution of fat in the lobule. The data support the idea that there is a link between CYP2E1 induction by ethanol and the early phase of ethanol-induced liver injury in this rat model. This link may involve lipid peroxidation, but other factors related to CYP2E1 induction must also be involved.

Original languageEnglish (US)
Pages (from-to)1610-1617
Number of pages8
JournalHepatology
Volume21
Issue number6
DOIs
StatePublished - 1995

Fingerprint

Cytochrome P-450 CYP2E1
Liver Diseases
Ethanol
Alcohols
Lipid Peroxidation
Liver
Pathology
Hydroxylation
Mixed Function Oxygenases
NADP
NAD
Isoenzymes
Proteins
Eating
Fats
Staining and Labeling
Messenger RNA
phenethyl isothiocyanate

ASJC Scopus subject areas

  • Hepatology

Cite this

Morimoto, M., Hagbjork, A. L., Wan, Y-J. Y., Fu, P. C., Clot, P., Albano, E., ... French, S. W. (1995). Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors. Hepatology, 21(6), 1610-1617. https://doi.org/10.1016/0270-9139(95)90466-2

Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors. / Morimoto, Michio; Hagbjork, Ann Louise; Wan, Yu-Jui Yvonne; Fu, Paul C.; Clot, Paolo; Albano, Emanuele; Ingelman-Sundberg, Magnus; French, Samuel W.

In: Hepatology, Vol. 21, No. 6, 1995, p. 1610-1617.

Research output: Contribution to journalArticle

Morimoto, M, Hagbjork, AL, Wan, Y-JY, Fu, PC, Clot, P, Albano, E, Ingelman-Sundberg, M & French, SW 1995, 'Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors', Hepatology, vol. 21, no. 6, pp. 1610-1617. https://doi.org/10.1016/0270-9139(95)90466-2
Morimoto, Michio ; Hagbjork, Ann Louise ; Wan, Yu-Jui Yvonne ; Fu, Paul C. ; Clot, Paolo ; Albano, Emanuele ; Ingelman-Sundberg, Magnus ; French, Samuel W. / Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors. In: Hepatology. 1995 ; Vol. 21, No. 6. pp. 1610-1617.
@article{eeed3d2c7580407d8b3937b7e0adb592,
title = "Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors",
abstract = "This study was done to determine if a relationship exists between CYP2E1 induction by ethanol, lipid peroxidation, and liver pathology in experimental alcohol-induced liver disease in the rat. Rats were fed ethanol with or without diallyl sulfide (DAS) or phenethyl isothiocyanate (PIC) intragastrically for 1 month. CYP2E1 induction by ethanol was correlated with lipid peroxidation, liver microsomal CYP2E1 hydroxylation of paranitrophenol, and the liver pathology score using the data from the PIC-fed rats. Some of the data from the ethanol and DAS-fed rats were not included here because they have been reported elsewhere. Microsomal CYP2E1 protein levels induction by ethanol was decreased by PIC ingestion. Similarly, PIC reduced the increase microsomal reduced form of nicotinamide-adenine dinucleotide (NADPH)-dependent lipid peroxidation and p-nitrophenol hydroxylase (PNPH) activity, induced by ethanol feeding. The lipid peroxidation was reduced to below control levels; however, the pathology score was partially but not significantly reduced by isothiocyanate feeding. CYP2E1 messenger RNA (mRNA) was decreased by both inhibitors of CYP2E1. Immunohistochemical staining of liver for CYP2E1 protein showed that the lobular distribution of the isozyme changed from the centrilobular to a diffuse pattern, with an increase in the periportal region when the CYP2E1 inhibitors were fed with ethanol, and that this change correlated with the change in the distribution of fat in the lobule. The data support the idea that there is a link between CYP2E1 induction by ethanol and the early phase of ethanol-induced liver injury in this rat model. This link may involve lipid peroxidation, but other factors related to CYP2E1 induction must also be involved.",
author = "Michio Morimoto and Hagbjork, {Ann Louise} and Wan, {Yu-Jui Yvonne} and Fu, {Paul C.} and Paolo Clot and Emanuele Albano and Magnus Ingelman-Sundberg and French, {Samuel W.}",
year = "1995",
doi = "10.1016/0270-9139(95)90466-2",
language = "English (US)",
volume = "21",
pages = "1610--1617",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors

AU - Morimoto, Michio

AU - Hagbjork, Ann Louise

AU - Wan, Yu-Jui Yvonne

AU - Fu, Paul C.

AU - Clot, Paolo

AU - Albano, Emanuele

AU - Ingelman-Sundberg, Magnus

AU - French, Samuel W.

PY - 1995

Y1 - 1995

N2 - This study was done to determine if a relationship exists between CYP2E1 induction by ethanol, lipid peroxidation, and liver pathology in experimental alcohol-induced liver disease in the rat. Rats were fed ethanol with or without diallyl sulfide (DAS) or phenethyl isothiocyanate (PIC) intragastrically for 1 month. CYP2E1 induction by ethanol was correlated with lipid peroxidation, liver microsomal CYP2E1 hydroxylation of paranitrophenol, and the liver pathology score using the data from the PIC-fed rats. Some of the data from the ethanol and DAS-fed rats were not included here because they have been reported elsewhere. Microsomal CYP2E1 protein levels induction by ethanol was decreased by PIC ingestion. Similarly, PIC reduced the increase microsomal reduced form of nicotinamide-adenine dinucleotide (NADPH)-dependent lipid peroxidation and p-nitrophenol hydroxylase (PNPH) activity, induced by ethanol feeding. The lipid peroxidation was reduced to below control levels; however, the pathology score was partially but not significantly reduced by isothiocyanate feeding. CYP2E1 messenger RNA (mRNA) was decreased by both inhibitors of CYP2E1. Immunohistochemical staining of liver for CYP2E1 protein showed that the lobular distribution of the isozyme changed from the centrilobular to a diffuse pattern, with an increase in the periportal region when the CYP2E1 inhibitors were fed with ethanol, and that this change correlated with the change in the distribution of fat in the lobule. The data support the idea that there is a link between CYP2E1 induction by ethanol and the early phase of ethanol-induced liver injury in this rat model. This link may involve lipid peroxidation, but other factors related to CYP2E1 induction must also be involved.

AB - This study was done to determine if a relationship exists between CYP2E1 induction by ethanol, lipid peroxidation, and liver pathology in experimental alcohol-induced liver disease in the rat. Rats were fed ethanol with or without diallyl sulfide (DAS) or phenethyl isothiocyanate (PIC) intragastrically for 1 month. CYP2E1 induction by ethanol was correlated with lipid peroxidation, liver microsomal CYP2E1 hydroxylation of paranitrophenol, and the liver pathology score using the data from the PIC-fed rats. Some of the data from the ethanol and DAS-fed rats were not included here because they have been reported elsewhere. Microsomal CYP2E1 protein levels induction by ethanol was decreased by PIC ingestion. Similarly, PIC reduced the increase microsomal reduced form of nicotinamide-adenine dinucleotide (NADPH)-dependent lipid peroxidation and p-nitrophenol hydroxylase (PNPH) activity, induced by ethanol feeding. The lipid peroxidation was reduced to below control levels; however, the pathology score was partially but not significantly reduced by isothiocyanate feeding. CYP2E1 messenger RNA (mRNA) was decreased by both inhibitors of CYP2E1. Immunohistochemical staining of liver for CYP2E1 protein showed that the lobular distribution of the isozyme changed from the centrilobular to a diffuse pattern, with an increase in the periportal region when the CYP2E1 inhibitors were fed with ethanol, and that this change correlated with the change in the distribution of fat in the lobule. The data support the idea that there is a link between CYP2E1 induction by ethanol and the early phase of ethanol-induced liver injury in this rat model. This link may involve lipid peroxidation, but other factors related to CYP2E1 induction must also be involved.

UR - http://www.scopus.com/inward/record.url?scp=0029016297&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029016297&partnerID=8YFLogxK

U2 - 10.1016/0270-9139(95)90466-2

DO - 10.1016/0270-9139(95)90466-2

M3 - Article

VL - 21

SP - 1610

EP - 1617

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 6

ER -