Pronounced hepatic free radical formation precedes pathological liver injury in ethanol-fed rats.
BACKGROUND
The role of free radicals in alcoholic liver injury remains uncertain. These experiments were conducted to measure radical formation in rats that were fed alcohol along with either fish oil or saturated fats, which cause different types of liver pathology.


METHODS
Liquid diets containing alcohol or isocaloric dextrose were administered to rats by intragastric infusion for 2 weeks. Radical intermediates detected by spin trapping were measured in bile.


RESULTS
In rats that were fed alcohol plus fish oil, biliary concentrations of trapped radicals, which most likely originated from lipids, were 6-fold higher than in controls that were fed fish oil plus dextrose. High rates of radical formation persisted 24 hr after alcohol withdrawal, when all alcohol had been metabolized. In contrast, diets containing alcohol and medium chain triglycerides did not stimulate lipid radical formation.


CONCLUSIONS
High rates of lipid radical formation were observed only in rats that were fed alcohol in combination with a fish oil diet, and a persistent flux of radical formation continued after alcohol withdrawal. These radical phenomena precede serious liver pathology, which develops after longer periods of fish oil plus alcohol diets.
Reinke
L A
LA
Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA. lester-reinke@oushc.edu
Moore
D R
DR
Nanji
A A
AA
D000818:Animals; D001646:Bile / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D005395:Fish Oils; D005609:Free Radicals; D000431:Ethanol