Abstract
The effects of p-tert-butylphenyl trans-4-guanidinomethyl cyclohexane carboxylate hydrochloride (NCO-650) on drug-metabolizing enzymes and fine structure in rat liver were investigated. Aminopyrine demethylase, cytochrome b5 and cytochrome P-450 contents increased by a single administration of NCO-650 (10, 100 and 1000 mg/kg, p. o.). NCO-650 caused the morphological changes of liver fine structure such as disarrangement of rough endoplasmic reticulum (rER), detachment of ribosome from the rER and increase in smooth endoplasmic reticulum. The increases in drug-metabolizing enzyme activities and morphological changes in rat liver by NCO-650 were not dose-dependently. Trimethadione metabolism was not accelerated by the administration of NCO-650. In those results, the morphological changes in liver by a single administration of NCO-650 seem to be a direct action on the membrane of hepatocytes and its organelle. The induction of drug-metabolizing enzyme contents by NCO-650 was suggested a transitory response with the morphological changes in the liver.
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