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PubMed1985

Inhibitory effect of propylthiouracil on the development of metabolic tolerance to ethanol.

Chronic ethanol administration (4-5 weeks) to female spontaneously hypertensive (SH) rats led to a marked increase in the rate of ethanol metabolism. This was accompanied by an increase in hepatic alcohol dehydrogenase (ADH) and by an increase in the rate of oxygen consumption in perfused livers of these animals. Treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU) during the last 9 days (40 mg/kg/day) of the chronic administration of ethanol reduced hepatic oxygen consumption, resulting in a net diminution of the metabolic tolerance to ethanol, despite a further elevation in ADH activity. In these animals, microsomal ethanol-oxidizing system (MEOS) activity was not affected by chronic ethanol administration or by treatment with PTU. Data strongly suggest that in the female SH rat all the metabolic tolerance to ethanol proceeds via the ADH pathway, and that the increase in hepatic oxygen consumption is more important in the development of metabolic tolerance to ethanol than the increased ADH levels.

Alcohol Dehydrogenase↗
PubMed1980

Correlation of plasma propylthiouracil levels with inhibition of thyroid hormone synthesis in the rat.

The inhibition of thyroid hormone synthesis was studied in relation to plasma levels of 6-n-propyl-2-thiouracil (PTU). Na 125I (5 muCi) was injected i.p. into adult male Sprague-Dawley rats. After 30 min, graded doses of PTU (0.2 mg/kg. 0.1 mg/kg, and 0.05 mg/kg) were similarly injected. Thyroid hormone synthesis was followed by the accumulation of radioactivity into thyroid glands, which were removed at specified time intervals. PTU levels were measured spectrophotometrically at the time of sacrifice. A-ditionally, PTU (35S) was used to confirm blood levels of PTU and also to follow intrathyroidal PTU levels. Plasma PTU levels in excess of 0.18 microgram/ml completely inhibited thyroid hormone synthesis. Levels between 0.14 and 0.09 microgram/ml had a partial effect, and PTU levels less than 0.09 microgram/ml had no effect on thyroid hormone synthesis.

Animals↗