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J. Biochem, 1974, Vol. 76, No. 4 735-744
© 1974 Japanese Biochemical Society

research-article

Induction by Phenobarbital of Hepatic Microsomal Drug-metabolizing Enzyme System in Partially Hepatectomized Rats

Yukinobu HINO, Yoshio IMAI and Ryo SATO

Institute for Protein Research, Osaka University Suita, Osaka 565

The induction by phenobarbital (PB) of microsomal drug-metabolizing enzymes in the residual portion of rat liver after partial hepatectomy was studied. Administration of PB 1 hr after surgery caused only a slight increase in the microsomal content of cytochrome P-450 during subsequent 48 hr, although the cytochrome was normally induced by PB given 1 hr after sham operation. This greatly reduced responsiveness to PB immediately after partial hepatectomy was, however, restored gradually as liver regeneration proceeded, and the liver regained the full capacity of PB-induced accumulation of cytochrome P-450 by the 4th day after the operation. Microsomal NADPH-cytochrome c reductase was not inducible by PB immediately after the surgical operation in both sham operated and partially hepatectomized rats; however, it became thereafter inducible gradually, though only to slight extents. Cytochrome b5 was not inducible throughout the regenerative process. The change in the ethyl isocyanide difference spectrum of reduced cytochrome P-450 following PB injection 4 days after partial hepatectomy was essentially similar to that in PB-treated sham operated rats. But in the induction immediately after partial hepatectomy no change was observed in the difference spectrum. The specific activity of aminopyrine N-demethylase of all the microsomal preparations examined in this study was virtually proportional to the specific content of cytochrome P-450.


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