Comparison of the effect of phenobarbital on the D-glucuronic acid pathway in euthyroid and hypothyroid rats.

Abstract

Abstract: Hypothyroidism was produced in male rats by thiouracil (50 mg/kg daily, i. g., for 1 month), in order to study the thyroid control of the D‐glucuronic acid pathway in the liver. The activities of UDPglucose dehydrogenase, UDPglucuronosyltransferase, UDPglucuronic acid pyrophosphatase, D‐glucuronolactone dehydrogenase and 3‐hydroxyacid dehydrogenase were significantly enhanced by hypothyroidism. In contrast, β‐glucuronidase activity was decreased while that of L‐gulonolactone dehydrogenase was not affected. The excretion of L‐ascorbic acid in the urine was unchanged and that of D‐glucaric acid was decreased. Phenobarbital administration (80 mg/kg daily, intraperitoneally, for 3 days) induced UDPglucuronosyltransferase and D‐glucuronolactone dehydrogenase activities both in euthyroid and hypothyroid animals. The excretion of L‐ascorbic acid in the urine failed to rise after phenobarbital treatment in the hypothyroid state, although it increased in animals with normal thyroid function. D‐Glucaric acid excretion in the urine was increased by phenobarbital to the same extent in hypothyroid and euthyroid animals. The results suggest that hypothyroidism accelerates the flow through the D‐glucuronic acid pathway and perhaps that further metabolism of free D‐glucuronic acid takes place mainly via the L‐xylulose route, due to the highly increased activity of 3‐hydroxyacid dehydrogenase. Phenobarbital administration mainly brings about the same effects on both euthyroid and hypothyroid animals. The exception is the lack of increase in the urinary excretion of L‐ascorbic acid during hypothyroidism.