Hepatic CYP3A expression and activity in low birth weight developing female rats

Zhi-Wei Zhu, Shao-Qing Ni, Xiu-Min Wang, Jue Wang, Su Zeng, Zheng-Yan Zhao

Hangzhou, China

Author Affiliations: Department of Children's Health and Care (Zhu ZW, Zhao ZY), Department of Clinical Pharmacology, the National Clinical Trial Institute (Ni SQ, Wang J), Department of Endocrinology (Wang XM), Children's Hospital of Zhejiang University School of Medicine and Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Diseases, Hangzhou 310003, China; Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China (Zeng S)

Corresponding Author: Su Zeng, Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, No. 388 Yu Hang Tang Road, Hangzhou 310058, China (Tel: +86 571 88208407; Email: nsqshc@163.com)

doi: 10.1007/s12519-013-0429-x

Background: We aimed to investigate the effects of low birth weight (LBW) on the hepatic expression of cytochrome P-450 3A (CYP3A) in developing female rats.

Methods: Pregnant rats were divided into two groups, a nourished group and an under-nourished group. The offspring of the nourished rats were defined as a normal weight, normal diet group (NN group). The offspring of the under-nourished rats were designated as a LBW, normal diet group (LN group). CYP3A mRNA expression, protein expression, protein localization and activity were determined.

Results: The CYP3A1 mRNA expression levels of the LN group on days 3, 21, and 56 were significantly higher than those of the same age in the NN group (P≤0.01). The mRNA expression of CYP3A2 in the LN group on day 21 was higher than in rats of the same age in the NN group (P<0.01). The staining intensity and frequency of CYP3A1-positive hepatocytes were significantly lower on days 7 and 21 in the LN group than those of rats of the same age in the NN group (P<0.05). The staining intensity and frequency of CYP3A2-positive hepatocytes on days 14 and 21 were higher in the LN group than those on the same days in the NN group  (P<0.05). The mean CYP3A activity of the LN group on day 3 was significantly higher than that of the NN group (P<0.001).

Conclusions: We found the effect of LBW on CYP3A activity was most prominent during the early days of life in rats. Investigators and clinicians should consider the effect of LBW on CYP3A in both pharmacokinetic study design and data interpretation, when prescribing drugs to LBW infants.

Key words: cytochrome P-450 3A; development; expression; low birth weight

World J Pediatr 2013;9(3):266-272