Interference of ethanol and sorbitol with hepatic ketone body metabolism in normal, hyper- and hypothyroid rats.

Abstract

Rats pretreated with triiodothyronine or propylthiouracil were compared with normal rats with respect to the changes induced by ethanol or sorbitol in the levels of ketone bodies and acetyl coenzyme A and in the mitochondrial redox state of the NAD couple in the intact liver after overnight fasting. A single dose of ethanol (2.5 g/kg) increased the ketone body level and the acetyl‐CoA content after 75 min in both normal and hyperthyroid rats but not in hypothyroid rats. Infusion of sorbitol (0.5 g/kg) resulted in decreases in both ketone formation and levels of acetyl‐CoA after 15 min in all types of rats. The β‐hydroxybutyrate/acetoacetate ratio, which represents the redox state of the NAD couple in the mitochondria, was increased more than three‐fold by treatment with ethanol in normal rats, but only by 50% in hyperthyroid rats. A ten‐fold increase in the redox state of the mitochoondia was caused by ethanol in hypothyroid rats, as the result of a strongly diminished acetoacetate level. Sorbitol infusion resulted in slight increase of the β‐hydroxybutyrate/acetoacetate ratio in normal and hypothyroid rats but decreased the ratio in hyperthyroid rats. The different ketone body levels observed in these situations were not found to be related to changes in the mitochondrial redox state, but a highly significant correlation (P < 0.001) was observed between the changes in the content of acetyl‐CoA and the ketone bodies.