Effects of ethanol on hepatic cellular replication and cell cycle progression

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

Ethanol is a hepatotoxin. It appears that the liver is the target of ethanol induced toxicity primarily because it is the major site of ethanol metabolism. Metabolism of ethanol results in a number of biochemical changes that are thought to mediate the toxicity associated with ethanol abuse. These include the production of acetaldehyde and reactive oxygen species, as well as an accumulation of nicotinamide adenine dinucleotide (NADH). These biochemical changes are associated with the accumulation of fat and mitochondrial dysfunction in the liver. If these changes are severe enough they can themselves cause hepatotoxicity, or they can sensitize the liver to more severe damage by other hepatotoxins. Whether liver damage is the result of ethanol metabolism or some other hepatotoxin, recovery of the liver from damage requires replacement of cells that have been destroyed. It is now apparent that ethanol metabolism not only causes hepatotoxicity but also impairs the replication of normal hepatocytes. This impairment has been shown to occur at both the G1/S, and the G2/M transitions of the cell cycle. These impairments may be the result of activation of the checkpoint kinases, which can mediate cell cycle arrest at both of these transitions. Conversely, because ethanol metabolism results in a number of biochemical changes, there may be a number of mechanisms by which ethanol metabolism impairs cellular replication. It is the goal of this article to review the mechanisms by which ethanol metabolism mediates impairment of hepatic replication.

Original languageEnglish (US)
Pages (from-to)4955-4959
Number of pages5
JournalWorld Journal of Gastroenterology
Volume13
Issue number37
DOIs
StatePublished - Oct 7 2007

Fingerprint

Cell Cycle
Ethanol
Liver
NAD
Acetaldehyde
Cell Cycle Checkpoints
Liver Diseases
Hepatocytes
Reactive Oxygen Species
Phosphotransferases
Fats

Keywords

  • Acetaldehyde
  • Alcoholic liver disease
  • Cell cycle
  • Cyclin-dependent kinases
  • Ethanol metabolism
  • Liver regeneration

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Effects of ethanol on hepatic cellular replication and cell cycle progression. / Clemens, Dahn L.

In: World Journal of Gastroenterology, Vol. 13, No. 37, 07.10.2007, p. 4955-4959.

Research output: Contribution to journalReview article

@article{b168c0d667824407b7c949c32011d6c8,
title = "Effects of ethanol on hepatic cellular replication and cell cycle progression",
abstract = "Ethanol is a hepatotoxin. It appears that the liver is the target of ethanol induced toxicity primarily because it is the major site of ethanol metabolism. Metabolism of ethanol results in a number of biochemical changes that are thought to mediate the toxicity associated with ethanol abuse. These include the production of acetaldehyde and reactive oxygen species, as well as an accumulation of nicotinamide adenine dinucleotide (NADH). These biochemical changes are associated with the accumulation of fat and mitochondrial dysfunction in the liver. If these changes are severe enough they can themselves cause hepatotoxicity, or they can sensitize the liver to more severe damage by other hepatotoxins. Whether liver damage is the result of ethanol metabolism or some other hepatotoxin, recovery of the liver from damage requires replacement of cells that have been destroyed. It is now apparent that ethanol metabolism not only causes hepatotoxicity but also impairs the replication of normal hepatocytes. This impairment has been shown to occur at both the G1/S, and the G2/M transitions of the cell cycle. These impairments may be the result of activation of the checkpoint kinases, which can mediate cell cycle arrest at both of these transitions. Conversely, because ethanol metabolism results in a number of biochemical changes, there may be a number of mechanisms by which ethanol metabolism impairs cellular replication. It is the goal of this article to review the mechanisms by which ethanol metabolism mediates impairment of hepatic replication.",
keywords = "Acetaldehyde, Alcoholic liver disease, Cell cycle, Cyclin-dependent kinases, Ethanol metabolism, Liver regeneration",
author = "Clemens, {Dahn L}",
year = "2007",
month = "10",
day = "7",
doi = "10.3748/wjg.v13.i37.4955",
language = "English (US)",
volume = "13",
pages = "4955--4959",
journal = "World Journal of Gastroenterology",
issn = "1007-9327",
publisher = "WJG Press",
number = "37",

}

TY - JOUR

T1 - Effects of ethanol on hepatic cellular replication and cell cycle progression

AU - Clemens, Dahn L

PY - 2007/10/7

Y1 - 2007/10/7

N2 - Ethanol is a hepatotoxin. It appears that the liver is the target of ethanol induced toxicity primarily because it is the major site of ethanol metabolism. Metabolism of ethanol results in a number of biochemical changes that are thought to mediate the toxicity associated with ethanol abuse. These include the production of acetaldehyde and reactive oxygen species, as well as an accumulation of nicotinamide adenine dinucleotide (NADH). These biochemical changes are associated with the accumulation of fat and mitochondrial dysfunction in the liver. If these changes are severe enough they can themselves cause hepatotoxicity, or they can sensitize the liver to more severe damage by other hepatotoxins. Whether liver damage is the result of ethanol metabolism or some other hepatotoxin, recovery of the liver from damage requires replacement of cells that have been destroyed. It is now apparent that ethanol metabolism not only causes hepatotoxicity but also impairs the replication of normal hepatocytes. This impairment has been shown to occur at both the G1/S, and the G2/M transitions of the cell cycle. These impairments may be the result of activation of the checkpoint kinases, which can mediate cell cycle arrest at both of these transitions. Conversely, because ethanol metabolism results in a number of biochemical changes, there may be a number of mechanisms by which ethanol metabolism impairs cellular replication. It is the goal of this article to review the mechanisms by which ethanol metabolism mediates impairment of hepatic replication.

AB - Ethanol is a hepatotoxin. It appears that the liver is the target of ethanol induced toxicity primarily because it is the major site of ethanol metabolism. Metabolism of ethanol results in a number of biochemical changes that are thought to mediate the toxicity associated with ethanol abuse. These include the production of acetaldehyde and reactive oxygen species, as well as an accumulation of nicotinamide adenine dinucleotide (NADH). These biochemical changes are associated with the accumulation of fat and mitochondrial dysfunction in the liver. If these changes are severe enough they can themselves cause hepatotoxicity, or they can sensitize the liver to more severe damage by other hepatotoxins. Whether liver damage is the result of ethanol metabolism or some other hepatotoxin, recovery of the liver from damage requires replacement of cells that have been destroyed. It is now apparent that ethanol metabolism not only causes hepatotoxicity but also impairs the replication of normal hepatocytes. This impairment has been shown to occur at both the G1/S, and the G2/M transitions of the cell cycle. These impairments may be the result of activation of the checkpoint kinases, which can mediate cell cycle arrest at both of these transitions. Conversely, because ethanol metabolism results in a number of biochemical changes, there may be a number of mechanisms by which ethanol metabolism impairs cellular replication. It is the goal of this article to review the mechanisms by which ethanol metabolism mediates impairment of hepatic replication.

KW - Acetaldehyde

KW - Alcoholic liver disease

KW - Cell cycle

KW - Cyclin-dependent kinases

KW - Ethanol metabolism

KW - Liver regeneration

UR - http://www.scopus.com/inward/record.url?scp=34848860809&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34848860809&partnerID=8YFLogxK

U2 - 10.3748/wjg.v13.i37.4955

DO - 10.3748/wjg.v13.i37.4955

M3 - Review article

C2 - 17854137

AN - SCOPUS:34848860809

VL - 13

SP - 4955

EP - 4959

JO - World Journal of Gastroenterology

JF - World Journal of Gastroenterology

SN - 1007-9327

IS - 37

ER -