Inducibility of the hepatic microsomal monooxygenase system experimentally reduced to a minimum amount/activity: Effect of hypophysectomy, partial hepatectomy and phenobarbital/toluene treatment on the hepatic polysubstrate monooxygenase system in rats

Abstract

Sham-operated, hypophysectomized, partially hepatectomized and hypophysectomized + partially hepatectomized groups of CFY rats were treated with phenobarbital (40 mg/kg/day) per os or physiological saline once a day, or toluene-vapour (inhalation: 4,000 mg/m3, 8 h/day), for 3 days. The polysubstrate monooxygenase (PSMO) system of the liver was induced by phenobarbital after all kinds of surgical interventions. Inducibility of the enzyme system was the highest in the group with combined hypophysectomy + partial hepatectomy and decreased in order in the groups with partial hepatectomy, hypophysectomy and sham-operation. The relative cytochrome P-450 content (quantity of cytochrome P-450/100 g b.w.) was the lowest after combined operation, higher in partially hepatectomized and hypophysectomized animals and it was the highest in the sham-operated group. Hypophysectomy after partial hepatectomy seems to inhibit hepatic regeneration and to increase the inducibility of the enzyme by phenobarbital, at the same time. Phenobarbital treatment brought about SER proliferation in a part of liver cells, in each group. In case of repeated liver damage due to the consequences of hypophysectomy, partial hepatectomy, phenobarbital administration, a group of the liver cells responds to the first, another to the second, but even after the third injury a group of the liver cells maintained its regular structure. The hypothetical hepatotoxic effect of toluene, a widely used industrial solvent, has been tested. Hepatotoxicity has been excluded. The minimum non-specific hepatotoxic effect of the solvent was not augmented by either partial hepatectomy or hypophysectomy, or by the combination of the two. In all the experimental groups toluene increased the hepatic cytochrome P-450 level and induced a moderate increase in SER. Inducibility of the enzyme system after toluene inhalation was similar to that of the enzyme system after phenobarbital treatment in each group.