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Establishment of Metabolism and Transport Pathways in the Rodent and Human Fetal Liver
Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Rd., Piscataway, NJ 08854, USA
Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Rd., Piscataway, NJ 08854, USA
* Author to whom correspondence should be addressed.
Received: 5 November 2013; in revised form: 25 November 2013 / Accepted: 26 November 2013 / Published: 6 December 2013
Abstract: The ultimate fate of drugs and chemicals in the body is largely regulated by hepatic uptake, metabolism, and excretion. The liver acquires the functional ability to metabolize and transport chemicals during the perinatal period of development. Research using livers from fetal and juvenile rodents and humans has begun to reveal the timing, key enzymes and transporters, and regulatory factors that are responsible for the establishment of hepatic phase I and II metabolism as well as transport. The majority of this research has been limited to relative mRNA and protein quantification. However, the recent utilization of novel technology, such as RNA-Sequencing, and the improved availability and refinement of functional activity assays, has begun to provide more definitive information regarding the extent of hepatic drug disposition in the developing fetus. The goals of this review are to provide an overview of the early regulation of the major phase I and II enzymes and transporters in rodent and human livers and to highlight potential mechanisms that control the ontogeny of chemical metabolism and excretion pathways.
Keywords: fetal; metabolism; transport; regulation; prenatal; phase I; phase II; Abc; Slc; ontogeny
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Moscovitz, J.E.; Aleksunes, L.M. Establishment of Metabolism and Transport Pathways in the Rodent and Human Fetal Liver. Int. J. Mol. Sci. 2013, 14, 23801-23827.
Moscovitz JE, Aleksunes LM. Establishment of Metabolism and Transport Pathways in the Rodent and Human Fetal Liver. International Journal of Molecular Sciences. 2013; 14(12):23801-23827.
Moscovitz, Jamie E.; Aleksunes, Lauren M. 2013. "Establishment of Metabolism and Transport Pathways in the Rodent and Human Fetal Liver." Int. J. Mol. Sci. 14, no. 12: 23801-23827.