Thyroid and liver trophic changes in rats secondary to liver microsomal enzyme induction caused by an experimental leukotriene antagonist (L-649,923)

摘要: Abstract Thyroid hyperplasia and/or hepatomegaly were observed in a 14-week oral toxicity study with L-649,923, leukotriene antagonist, at doses of 50 and 150 mg/kg/day. In 16-day study, L-649,923 caused an increase plasma TSH hepatic enzyme induction, but did not affect T 3 4 levels. Light microscopy ultrastructural examination the liver thyroid showed changes indicative induction increased stimulation by TSH. Because other inducers cause increasing turnover it was hypothesized that L-649,923-induced might be occurring same mechanism. To examine this theory, rats treated po 300 mg/kg/day for 17 days. On Day 15, all dosed iv [ 125 I]thyroxine (33 μCi/rat). At various times after dosing, blood collected levels I determined. The clearance elimination rate constant significantly larger animals than control group ( p ). This work demonstrates increases thyroxine which is associated hyperplasia.