Changes in thyroidal function and liver UDPglucuronosyltransferase activity in rats following administration of a novel imidazole (SC-37211)

Toxicol Appl Pharmacol. 1985 Sep 30;80(3):427-36. doi: 10.1016/0041-008x(85)90387-4.

Abstract

SC-37211, an imidazole with antianaerobic activity, was administered po to male rats for 2 weeks at dosages of 20, 60, and 200 mg/kg/day. Histological changes in the thyroid included irregularly shaped follicles and slightly enlarged follicular cells. Serum triiodothyronine (T3) and/or thyroxine (T4) were significantly decreased in treated animals at all dosages; these decreases were not observed following a 2-week recovery period. The half-life of serum [125I]thyroxine was also significantly decreased in rats treated with SC-37211. Morphological changes in the thyroid are likely the result of thyroid-stimulating hormone (TSH) stimulation, a response to decreased serum T3 and T4 concentrations. The decreases in T3 and T4 were not due to decreases in iodide uptake or organification. There were dose-dependent increases in liver weights, liver-to-body weight ratios, and UDPglucuronosyltransferase activity toward p-nitrophenol and T4. Therefore, the decreases in serum T3 and T4 were probably due to an increase in hepatic metabolism rather than to a direct effect of SC-37211 on the thyroid.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Dose-Response Relationship, Drug
  • Glucuronosyltransferase / metabolism*
  • Half-Life
  • Imidazoles / pharmacology*
  • Iodides / metabolism
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Microscopy, Electron
  • Nitrophenols / metabolism
  • Organ Size / drug effects
  • Rats
  • Rats, Inbred Strains
  • Thyroid Gland / drug effects*
  • Thyroid Gland / physiology
  • Thyrotropin / pharmacology
  • Thyroxine / blood
  • Triiodothyronine / blood

Substances

  • Imidazoles
  • Iodides
  • Nitrophenols
  • Triiodothyronine
  • Thyrotropin
  • SC 37211
  • Glucuronosyltransferase
  • Thyroxine
  • 4-nitrophenol