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Effect of Neonatal Exposure of 17β-Estradiol Tamoxifen on Hepatic CYP3A Activity at Developmental Periods in Rats

Drug Metabolism and Pharmacokinetics, ISSN: 1347-4367, Vol: 19, Issue: 2, Page: 96-102
2004
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Article Description

We evaluated hepatic CYP3A activity during development in male and female rats and the effect of neonatal exposure of 17 β -estradiol and tamoxifen. In untreated and olive oil-treated (control) rats, hepatic CYP3A activities evaluated by erythromycin metabolism in vitro increased several-fold from age 2 to 9 weeks in males. In contrast, activity in females remained at a low and constant level from 2 to 15 weeks. Exposure of 17 β -estradiol to neonates at a dose of 10 μ mol Wkg daily for 3 days on day 1 ~ 3 or 4 ~ 6 after birth significantly increased hepatic CYP3A activity during the developmental period in both males and females, and a greater influence was observed in females exposed during days 4 ~ 6. Pubertal exposure of 17 β -estradiol (7-weeks old, 10 μ mol Wkg daily for 3 days) also increased hepatic CYP3A activity, but only in females. Neonatal exposure to tamoxifen (10 μ mol Wkg daily for 3 days) showed no appreciable effect in either males or females. In conclusion, a marked sex-difference was observed in hepatic CYP3A activity, and exposure of 17 β -estradiol to neonates increased hepatic CYP3A activity during the developmental period, especially in female rats.

Bibliographic Details

Murakami, Teruo; Sato, Akiko; Inatani, Michiyasu; Sakurai, Hanao; Yumoto, Ryoko; Nagai, Junya; Takano, Mikihisa

Japanese Society for the Study of Xenobiotics

Pharmacology, Toxicology and Pharmaceutics; Medicine

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