Peer Review #1 of "Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats (v0.2)"

Abstract

Cytochrome P450s (CYPs) are phase-I metabolic enzymes playing important roles in drug metabolism, dietary chemicals and endogenous molecules. Age is a key factor influencing P450s expression. Thus, age-related changes of CYP 1-4 families and bile acid homeostasis-related CYPs, the corresponding nuclear receptors and a few phase-II genes were examined. Livers from male Sprague-Dawley rats at fetus (-2 d), neonates (1, 7, and 14 d), weanling (21 d), puberty (28 and 35 d), adulthood (60 and 180 d), and aging (540 and 800 d) were collected and subjected to qPCR analysis. Liver proteins from 14, 28, 60, 180, 540 and 800 days of age were also extracted for selected protein analysis by Western-blot. In general, there were three patterns of their expression: Some of the drugmetabolizing enzymes and related nuclear receptors were low in fetal and neonatal stage, increased with liver maturation and decreased quickly at aging (AhR,