Factors affecting the properties of mixed-function oxidases in the liver and small intestine of neonatal rabbits.

In neonatal rabbits, quantitative increases in various mixed-function oxidase components accompanied the age-dependent increases in xenobiotic metabolism during the postnatal period. In addition to these quantitative changes, alterations in the nature of the type I and type II spectral interactions of substrates with hepatic cytochrome P-450 occurred during development, as did changes in the sensitivity of the hepatic mixed-function oxidase system to the inhibitory effects of carbon monoxide and SKF 525-A. The activity of the neonatal hepatic mixed-function oxidase system was reduced by feeding rabbits a semipurified diet, but not by withholding solid food, whereas the same dietary manipulations produced the converse effects in intestinal tissue. In contrast, recognized inducing agents (e.g., phenobarbital and 3-methylcholanthrene) markedly affected hepatic but not intestinal mixed-function oxidase activities in neonatal animals, whereas dexamethasone, a potent synthetic glucocorticoid, was equally effective in increasing both hepatic and intestinal activities. Consequently, there appears to be some common and some tissue-specific mechanisms controlling the qualitative and quantitative changes which characterize the development of mixed-function oxidases in the neonate.