Effects of propylthiouracil on D-Galactosamine hepatotoxicity in the rat evidence for a non-thyroidal effect

The cytoprotective effects of propylthiouracil (PTU) were studied in rats treated with the hepatotoxin D-galactosamine (D-GNH₂). Five days of PTU pretreatment prior to D-GNH₂ caused hypothyroidism and a significant reduction in liver injury as assessed by serum transaminase levels. When PTU was administered as a single dose with d-gnh₂, significant decreases in transaminase also occurred at times when thyroid function was unchanged. Furthermore, aminopyrine oxidation showed significant impairment after D-GNH₂ and was normalized by one dose of PTU. Further studies were carried out in thyroidectomized rats. PTU caused significant reductions in transaminase levels when given for 5 days pretreatment or as a single dose. Animals receiving pretreatment with PTU plus thyroxine (T₄) also had significant decreases in serum transaminase. The antithyroid drug methimazole also had a hepatoprotective effect, while two other potent antithyroid compounds (2-thiouracil and 2-thiobarbituric acid) did not. These data suggest that PTU can protect against liver injury induced by D-GNH₂, that the effect is independent of thyroid function, and that this effect is not common to all thiolcontaining antithyroid drugs.