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Effects of p-tert-butylphenyl trans-4-guanidinomethylcyclohexane carboxylate hydrochloride (NCO-650) and its metabolite, p-tert-butylphenol(BP) on drug-metabolizing enzymes and fine structure in rat liver.

The effects of p-tert-butylphenyl trans-4-guanidinomethylcyclohexane carboxylate hydrochloride (NCO-650) and its metabolite, p-tert-butylphenol(BP), on the drug-metabolizing enzymes and fine structure in the rat liver were examined. Aminopyrine demethylase activity was inhibited by the administration of NCO-650 and BP at a dose of 2 and 10 mg/kg, p.o. The increases of microsomal cytochrome b5 and cytochrome P-450 contents were noticed at 1, 12 and 24 hr after NCO-650 and BP administration. Ascorbate-dependent lipid peroxidation of mitochondria and microsome increased by the administration of NCO-650 and BP, but NADPH-dependent lipid peroxidation decreased by these drugs. In the morphological observations of fine structure in the liver, NCO-650 and BP caused the swelling and decrease of rough endoplasmic reticulum and the increase of smooth endoplasmic reticulum. The morphological changes of liver fine structure were related to the changes of drug-metabolizing enzymes in the liver by the administration of NCO-650 and BP, which may be suggest the transitory and functional responses of these drugs in the liver. The effect of BP on the drug-metabolizing enzymes and fine structure in the liver was similar to that of NCO-650.