Ontogeny of mammalian metabolizing enzymes in humans and animals used in toxicological studies

摘要

It is well recognized that expression of enzymes varies during development and growth. However, an in-depth review of this acquired knowledge is needed to translate the understanding of enzyme expression and activity into the prediction of change in effects (e.g. kinetics and toxicity) of xenobiotics with age. Age-related changes in metabolic capacity are critical for understanding and predicting the potential differences resulting from exposure. Such information may be especially useful in the evaluation of the risk of exposure to very low (μg/kg/day or ng/kg/day) levels of environmental chemicals. This review is to better understand the ontogeny of metabolizing enzymes in converting chemicals to either less-toxic metabolite(s) or more toxic products (e.g. reactive intermediate[s]) during stages before birth and during early development (neonate/infant/child). In this review, we evaluated the ontogeny of major "phase I" and "phase II" metabolizing enzymes in humans and commonly used experimental animals (e.g. mouse, rat, and others) in order to fill the information gap.