HEAT-SHOCK GENE-EXPRESSION IN ALCOHOLIC LIVER-DISEASE IN THE RAT IS RELATED TO THE SEVERITY OF LIVER-INJURY AND LIPID-PEROXIDATION

To evaluate the relationship between heat-shock gene expression and the severity of pathologic liver injury and lipid peroxidation in experimental alcoholic liver disease, we used the intragastric-feeding rat model, Six groups of male Wistar rats weighing between 225 and 250 g were fed liquid diets containing different dietary fats (saturated fat, corn oil, and fish oil) and ethanol or dextrose for 1 month. Pathologic injury, mRNA and protein levels of HSP70, microsomal conjugated dienes, and hydrogen peroxide were evaluated at sacrifice. Fish oil-ethanol fed rats developed the most severe injury, while the saturated fat-ethanol group showed no liver injury, The highest levels of HSP70 mRNA were seen in the fish oil-ethanol group, There was no difference in HSP70 protein levels between the groups, The levels of HSP70 mRNA correlated significantly with microsomal conjugated dienes (r = 0.87, P < 0.01) and hydrogen peroxide (r = 0.90, P < 0.01). Increased centrilobular HSP70 expression was seen in rats showing liver injury, The close relationship seen between oxidant stress and HSP70 mRNA but not protein suggest that the binding of HSP70 protein to other damaged proteins reduces free HSP70 protein leading to increased HSP70 expression, HSP70 expression may also be a cellular adaptive response to ethanol-induced oxidative stress.