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 thiol-containing antithyroid drugs.
D000631:Aminopyridines / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005688:Galactosamine / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D010084:Oxidation-Reduction; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013961:Thyroid Gland / Q000187:drug effects*; D013965:Thyroidectomy
D000631:Aminopyridines; D011441:Propylthiouracil; D005688:Galactosamine; D004247:DNA; D001219:Aspartate Aminotransferases