Development and differentiation of bile ducts in the mammalian liver

Shiojiri, Nobuyoshi

doi:10.1002/(sici)1097-0029(19971115)39:4<328::aid-jemt3>3.0.co;2-d

Cited by 132 publications

(109 citation statements)

References 51 publications

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“…Expression of CYP2C protein and activity in foetal liver appears to be negligible (Ratanasavanh et al 1991;Hakkola et al 1994;Treluyer et al 1996Treluyer et al & 1997. CYP2C mRNA and protein expression are significantly elevated as early as the first postnatal day (Ratanasavanh et al 1991, Treluyer et al 1996& 1997, protein expression increases during the first week and CYP2C activity (tolbutamide hydroxylation) surges after the first week and remains at about 40% of the adult level during the first year (Treluyer et al 1997).…”

Section: Cytochrome P450 In the Neonatal Human Livermentioning

confidence: 99%

“…Sinusoidal fenestrations increase in density in the early postnatal period, coincident with the establishment of zonation of hepatocellular metabolic activity within the acinus (Barbera-Guillem et al 1986). Bile canalicular and intrahepatic bile duct structure and function are immature in the liver of the newborn mammal, and differentiation and development of the intrahepatic bile ducts continue for 1-2 weeks after birth in the mouse and rat liver (Shiojiri 1997).…”

Section: Hepatic Physiologymentioning

confidence: 99%

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Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

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After the transition from in utero to newborn life, the neonate becomes solely reliant upon its own drug clearance processes to metabolise xenobiotics. Whilst most studies of neonatal hepatic drug elimination have focussed upon in vitro expression and activities of drug-metabolising enzymes, the rapid physiological changes in the early neonatal period of life also need to be considered. There are dramatic changes in neonatal liver blood flow and hepatic oxygenation due to the loss of the umbilical blood supply, the increasing portal vein blood flow, and the gradual closure of the ductus venosus shunt during the first week of life. These changes which may well affect the capacity of neonatal hepatic drug metabolism. The hepatic expression of cytochromes P450 1A2, 2C, 2D6, 2E1 and 3A4 develop at different rates in the postnatal period, whilst 3A7 expression diminishes. Hepatic glucuronidation in the human neonate is relatively immature at birth, which contrasts with the considerably more mature neonatal hepatic sulfation activity. Limited in vivo studies show that the human neonate can significantly metabolise xenobiotics but clearance is considerably less compared with the older infant and adult. The neonatal population included in pharmacological studies is highly heterogeneous with respect to age, body weight, ductus venosus closure and disease processes, making it difficult to interpret data arising from human neonatal studies. Studies in the perfused foetal and neonatal sheep liver have demonstrated how the oxidative and conjugative hepatic elimination of drugs by the intact organ is significantly increased during the first week of life, highlighting that future studies will need to consider the profound physiological changes that may influence neonatal hepatic drug elimination shortly after birth.The development of clinical pharmacology has resulted in a more rational approach to drug therapy, as well as a deeper understanding of the factors capable of influencing drug disposition, and hence drug effects. Of these factors, age is of great importance. However, substantial differences in drug disposition not only exist between neonates and adults, but also among premature neonates, term neonates, infants and children.During the last two decades drug disposition in the neonatal period has been studied extensively. A major impetus for these studies seems to have been a series of incidents involving illness or death following the administration of drugs at ratios of dose/body weight innocuous in an adult (Craft et al. 1974;Gershanik et al. 1982). These studies have shown that the transition from neonate to childhood is characterised by the ontogeny of all of the processes of drug absorption, distribution, hepatic metabolism and renal excretion, with the development of hepatic drug metabolism being particularly important.The extent to which the neonatal drug-metabolising en-

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Section: Cytochrome P450 In the Neonatal Human Livermentioning

confidence: 99%

Section: Hepatic Physiologymentioning

confidence: 99%

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

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“…The result of liver morphogenesis is the formation of hepatic plates, sinusoids and eventually the complex vascular and biliary network that is so crucial for normal liver function (Enzan et al, 1997;Shiojiri, 1997). The molecular events governing liver morphogenesis remain largely ill-defined.…”

Section: Duncanmentioning

confidence: 99%

Transcriptional regulation of liver development

Duncan¹

2000

Dev. Dyn.

102

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“…The liver forms from an endodermal outgrowth of primitive foregut around the third to fourth week gestation (1). Hepatoblasts, the pluripotent cells of the outgrowth, give rise to both hepatic and biliary cells.…”

Section: Introductionmentioning

confidence: 99%

“…The ductal plate cells migrate into surrounding mesenchyme to form intrahepatic bile ducts. Those cells not in contact with the portal mesenchyme differentiate into hepatocytes (1). During the fifth week of human gestation hematopoiesis moves from the yolk sac and/or adreno-gonadal-mesonephric (AGM) to the liver.…”

Section: Introductionmentioning

confidence: 99%