Effects of chemical agents on the hepatotoxicity and hepatic accumulation of luteoskyrin

Pretreatment of male mice with 3-methylcholanthrene and promethazine prevented the hepatic accumulation and the hepatotoxicity of luteoskyrin, while piperonyl butoxide and cobaltous chloride had no effect on either. Pretreatment with SKF-525 A elevated SGPT activity in male and female mice. Pretreatment with cycloheximide increased hepatic luteoskyrin accumulation in male mice. Dibenamine prevented hepatic luteoskyrin accumulation and hepatotoxicity only when it was injected in two doses, one the day before and the other concurrently with luteoskyrin. The data suggest that biliary excretion of luteoskyrin may be stimulated by an enzyme other than the microsomal drug metabolizing enzymes. 3-Methylcholanthrene, promethazine and dibenamine may accelerate this excretion thus protecting against luteoskyrin-induced hepatotoxicity. Cycloheximide may prevent this excretory process. The microsomal drug metabolizing enzymes may participate in the detoxification processes of the active form of luteoskyrin.