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 fro m gut bacteria or membrane permeability of the gut to endotoxin, or bo th. Female rats are more sensitive to these changes. Elevated levels o f endotoxin activate Kupffer cells to release substances such as eicos anoids, tumor necrosis factor-alpha and free radicals. Prostaglandins increase oxygen uptake and most likely are responsible for the hyperme tabolic state in the liver. The increase in oxygen demand leads to hyp oxia in the liver, and on reperfusion, alpha-hydroxyethyl free radical s are formed that lead to tissue damage in oxygen-poor pericentral reg ions of the liver lobule.