EFFECT OF PROPYLTHIOURACIL ON THE ETHANOL-INDUCED INCREASE IN LIVER OXYGEN-CONSUMPTION IN AWAKE RATS

It has been postulated that the beneficial effects of the antithyroid drug propylthiouracil in the treatment of alcoholic liver disease depe nd primarily on the action of propylthiouracil in suppressing the incr ease in hepatic oxygen consumption induced by ethanol. The evidence fo r this effect of propylthiouracil is derived from studies in which liv er oxygen consumption has been determined in in vitro preparations. In our study the effects of ethanol and propylthiouracil on liver oxygen consumption were assessed in vivo in an unrestrained and unanesthetiz ed rat model, where liver blood flow and hepatic vein and portal vein oxygen content can be measured. Data show that the liver oxygen consum ption increased in rats treated with ethanol-containing liquid diets f or 4 to 6 wk, both on withdrawal of alcohol (30%, p < 0.01), and after readministration of ethanol (50%, p < 0.01). Single-dose ethanol admi nistration increased portal tributary blood flow without affecting hep atic arterial blood flow in both controls and rats withdrawn from long -term ethanol treatment. Long-term ethanol administration per se had n o effect on portal tributary blood flow; however, hepatic arterial blo od flow was increased by 38% (p < 0.01). Treatment with propylthiourac il for 5 days resulted in complete suppression of the increase in live r oxygen consumption induced by long-term ethanol administration. Prop ylthiouracil treatment also attenuated the increase in portal tributar y blood flow after the administration of a single dose of ethanol. The se determinations were made 24 hr after the last dose of propylthioura cil. In conclusion, use of a new in vivo model with unrestrained and u nanesthetized rats has confirmed that long-term administration of etha nol increases liver oxygen consumption. For the first time, it has bee n shown in vivo that propylthiouracil abolishes the ethanol-induced in crease in liver oxygen consumption that follows long-term ethanol admi nistration.