Effects of pretreatment with SKF-525A, N-Methyl-2-thioimidazole, sodium phenobarbital, or methyl cholanthrene on ethylenethiourea-induced teratogenicity in rats.

Abstract

SKF-525A (SKF), a well known inhibitor of P450 function, and N-methyl-2 thioimidazole (MMI), an antithyroid drug resembling ethylenethiourea, were tested at the respective dosages of 40 Mg/kg ip and 200 mg/kg po, for their individual or combined effect on the teratogenicity on an oral dose of 60 mg/kg ethylenethiourea (ETU). All chemicals were dissolved in distilled water and administered to rats on the 13th day of pregnancy. MMI and ETU were dosed simultaneously, one hour after dosing with SKF. Control groups were given equivalent doses of ETU (positive control), SKF, MMI, or SKF+MMI. Term fetuses were evaluated for anomalies according to the established procedures. No teratogenic activity was attributed to treatments with SKF, or MMI, of their combination. However, in the remaining test groups, MMI+SKF+ETU+, or SKF+ETU, the type, incidence, and intensity of anomalies, compared to the group given only ETU, were markedly increased and were similar to those previously reported to occur at 120 mg/kg or higher doses of ETU. Pretreatment with either 40, 60, or 80 mg/kg of sodium phenobarbital injected once or twice a day on days 9-12 of pregnancy, or 20 mg/kg/day of methylcholanthrene on days 11-13 of pregnancy, failed to alter significantly the teratogenicity of a subsequent dose of 60 mg/kg of ETU given orally on the 13th day of pregnancy.