Zonation of the drug-metabolizing enzyme cytochrome P450 3A in infant mice begins in pre-weaning period

Abstract

The drug-metabolizing enzyme CYP3A is a heterogeneous enzyme found in the liver that displays local characteristics referred to as “zonation.” Zonation contributes to improved energy efficiency in metabolism. The objective of this study was to determine a scientific basis for the safety of fetuses and nursing infants in cases in which the use of pharmaceuticals by pregnant and nursing mothers is unavoidable. In addition, we analyzed CYP3A zonation in the liver using mice from the fetus stage to the nursing stage. The livers of mice ranging from day 13.5 of the fetal stage to day 7 of the nursing stage were resected and immunostained using rabbit anti-rat CYP3A2 Ab, which can detect CYP3A11, CYP3A13, CYP3A16, CYP3A25, CYP3A41 and CYP3A44. The results indicated that zonation did not begin in the fetus stage up to day 3 of the nursing stage, and began on day 7 of infancy. This study revealed that changes in the metabolic activity of CYP3A in the liver between the fetal and nursing stages are partly related to zonation. Further studies are needed to establish standards for the proper use of pharmaceuticals by pregnant and nursing mothers.