Abstract
Pretreatment of female rats with sodium phenobarbital (80 mg per kg) daily for 4 days markedly reduces the fatty liver resulting from a single dose of ethanol (4.8 g per kg). Inhibition of the ethanol- induced hepatic triglyceride accumulation is demonstrable after 3 days of phenobarbital pretreatment and is accompanied by alterations of the endoplasmic reticulum of the hepatocyte. The inhibition of the fatty liver is associated with a striking elevation of blood ethanol levels and no increase in blood lactate. The enhanced incorporation of fatty acid into triglyceride by microsomal preparations after in vivo ethanol administration did not occur in phenobarbital-pretreated animals. The oxidation of ethanol by liver slices and supernatant fractions was diminished in phenobarbital-pretreated animals and this inhibition also was demonstrable when phenobarbital was added in vitro to slices and supernatant fractions of control animals. However, ethanol oxidation by hepatic microsomes was similar in phenobarbital- and saline-pretreated rats and was not affected by addition of phenobarbital in vitro. It is suggested that the inhibitory effect of phenobarbital pretreatment on the ethanol-induced fatty liver is due to inhibition of the alcohol dehydrogenase-mediated oxidation of ethanol.
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