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Effects of intrauterine undernutrition on the expression of CYP3A23/3A1, PXR, CAR and HNF4α in neonate rats
Author(s) -
Ni Shaoqing,
Wang Xiumin,
Wang Jue,
Lu Sijie,
Zeng Su,
Zhao Zhengyan,
Yu Lushan,
Chen Shuqing
Publication year - 2008
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.635
Subject(s) - pregnane x receptor , malnutrition , expression (computer science) , medicine , endocrinology , pharmacology , biology , genetics , computer science , gene , transcription factor , nuclear receptor , programming language
Cytochrome P‐450 3A (CYP3A) together with its nuclear receptors plays a critical role in drug metabolism. The present study investigated the effects of undernutrition in utero on hepatic mRNA and protein expression of the enzyme CYP3A23/3A1 and nuclear receptors including pregnane X receptor (PXR; NR1I2 ), constitutive androstane receptor (CAR; NR1I3 ) and nuclear factor‐4alpha (HNF4α; HNF4A ) in neonatal rats. At gestational day 2, pregnant rats were randomly divided into two groups: nourished (fed ad libitum ) and undernourished (50% of nourished group). The pups delivered by nourished rats were designated as the normal‐birth‐weight group (NBW, n =15) and those delivered by undernourished rats were designated as the low‐birth‐weight group (LBW, n =15). Hepatic mRNA expression was detected by quantitative real‐time PCR and the corresponding protein expression was examined by immunohistochemistry (IHC). Compared with NBW pups, LBW pups tended to have lower mRNA expression levels of CYP3A23/3A1, PXR and CAR but higher levels of HNF4α. Only the CAR mRNA expression differences were significant ( p <0.05). mRNA expression of CYP3A23/3A1 correlated with that of HNF4α in both the LBW( r= 0.808, p= 0.007) and NBW ( r= 0.452, p= 0.012) groups. CYP3A23/3A1 and CAR protein expression differed between the two groups (CYP3A23/3A1, χ 2 = 7.87, p= 0.005; CAR, χ 2 = 12.069, p= 0.001). In conclusion, these findings suggest that undernutrition may influence the mRNA expression of CAR and protein expression of both CYP3A23/3A1 and CAR in neonatal rats. Since CYP3A23/3A1 and CAR are critically involved in drug metabolism, these results may have clinical implications for optimal medication in LBW children. Copyright © 2008 John Wiley & Sons, Ltd.