Role of Kupffer cells, endotoxin and free radicals in hepatotoxicity due to prolonged alcohol consumption: studies in female and male rats.
Alcohol ingestion results in increases in the release of endotoxin from gut bacteria or membrane permeability of the gut to endotoxin, or both. Female rats are more sensitive to these changes. Elevated levels of endotoxin activate Kupffer cells to release substances such as eicosanoids, tumor necrosis factor-alpha and free radicals. Prostaglandins increase oxygen uptake and most likely are responsible for the hypermetabolic state in the liver. The increase in oxygen demand leads to hypoxia in the liver, and on reperfusion, alpha-hydroxyethyl free radicals are formed that lead to tissue damage in oxygen-poor pericentral regions of the liver lobule.
Thurman
R G
RG
Department of Pharmacology, University of North Carolina at Chapel Hill 27599-7365, USA.
Bradford
B U
BU
Iimuro
Y
Y
Knecht
K T
KT
Connor
H D
HD
Adachi
Y
Y
Wall
C
C
Arteel
G E
GE
Raleigh
J A
JA
Forman
D T
DT
Mason
R P
RP
D000818:Animals; D001419:Bacteria / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism*; D005260:Female; D005609:Free Radicals; D000860:Hypoxia; D007422:Intestines / Q000382:microbiology; D007728:Kupffer Cells / Q000502:physiology*; D008108:Liver Diseases, Alcoholic / Q000209:etiology*; D008297:Male; D051381:Rats; D012727:Sex Characteristics
D004731:Endotoxins; D005609:Free Radicals