Cytochrome P-450-Dependent Monooxygenase Activities in Prenatal and Postnatal Human Livers: Comparison of Human Liver 7-Alkoxycoumarin O-Dealkylases with Rat Liver Enzymes

Matsubara, Takashi; Yamada, Noriko; Mitomi, Toshio; Yokoyama, Sho; Fukiishi, Yonetaka; Hasegawa, Yasuhiko; Nishimura, Hideo

doi:10.1254/jjp.40.389

Cited by 12 publications

(6 citation statements)

References 36 publications

(20 reference statements)

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“…Our observations showing high levels of both protein and mRNAs corresponding to P-450 IIIA agrees with these previous findings (35). In contrast, other P-45Mependent enzymes such as certain 7-alkoxycoumarin 0-dealkylase and aryl hydrocarbon hydroxylase (35,41) are very low, if present at all. According to Cresteil et al (34), the lack of aryl hydrocarbon hydroxylase is mainly caused by the lack of P-450 IA and P-450 IIC.…”

Section: Discussionsupporting

confidence: 92%

“…Unlike the fetal rodent liver, the fetal human liver exhibits some P-450-dependent monoxygenase reactions, particularly those supported by P-450 IIIA enzymes (34). Our observations showing high levels of both protein and mRNAs corresponding to P-450 IIIA agrees with these previous findings (35). In contrast, other P-45Mependent enzymes such as certain 7-alkoxycoumarin 0-dealkylase and aryl hydrocarbon hydroxylase (35,41) are very low, if present at all.…”

Section: Discussionsupporting

confidence: 89%

“…A number of studies have demonstrated species differences in the appearance of drug-metabolizing enzyme activities in the developing liver (34,35) and the heterogeneous intralobular distribution of these enzymes in the liver of adult laboratory animals (2,(36)(37)(38)(39)(40). The results of this study on quantitation and distribution of several P-450 enzymes, epoxide hydrolase and NADPH-P-450 reductase in the human liver show striking development-related differences and a heterogeneous intralobular distribution after birth that results in higher amounts of enzyme in the centrilobular zone.…”

Section: Discussionmentioning

confidence: 99%

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Intralobular distribution and quantitation of cytochrome P-450 enzymes in human liver as a function of age

et al. 1991

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We have used immunohistochemical, immunoblotting and messenger RNA blotting approaches to study the distribution and quantitation of three cytochrome P-450 enzymes, namely P-450 IA2, P-450 IIC and P-450 IIIA and, for comparison, epoxide hydrolase and NADPH-cytochrome P-450 reductase in human liver. Age-related changes in both the amounts and the intralobular distributions of these enzymes were demonstrated, and the enzymes differ in these regards: In fetal liver, P-450 IA2 and P-450 IIC were very low, when present at all, whereas P-450 IIIA, epoxide hydrolase and the reductase were already abundant and found in all the hepatocytes. During the postnatal period, P-450 IIC dramatically increased and was observed in all hepatocytes, the centrilobular ones being more intensely stained. P-450 IIIA was restricted to centrilobular and midzonal hepatocytes in normal adult liver. P-450 IA2 showed this same intralobular distribution; however, its presence was detected only several weeks or months after birth as judged both by immunohistochemical and immunoblotting techniques. Epoxide hydrolase and NADPH-cytochrome P-450 reductase were easily visualized in all hepatocytes regardless of the age of the donor; in child and adult livers, centrilobular hepatocytes were more intensely stained. Immunoreactive protein contents and corresponding messenger RNA levels correlated well with immunohistochemical observations. No major modification was seen in fibrotic liver, whereas both positive and negative cells were observed in cirrhotic liver nodules for all enzymes studied.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Intralobular distribution and quantitation of cytochrome P-450 enzymes in human liver as a function of age

et al. 1991

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“…Total enzyme activity in Sprague-Dawley rats on postnatal day 3 has been shown to be about one fifth of the activity attained in later development. 28 This also explains the lack of increased effect of codeine when using higher doses, up to 30 mg/kg at this age, because metabolic capacity may not be changed by an increase in substrate availability. As in adults, Dark Agouti infant rats might have been expected to have a poor response to codeine; paradoxically, a relative increase in efficacy was observed at 10 and 21 days.…”

Section: Discussionmentioning

confidence: 86%

Developmental Regulation of Codeine Analgesia in the Rat

Williams¹,

Dickenson²,

Fitzgerald

et al. 2004

Anesthesiology

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“…La concentración de ligandina o péptido y puede influir en la metabolización de fármacos en el hígado fetal. Esta proteína básica es la responsable de la captación de sustratos por las células metabolizadoras, la ligandina se une a la bilirrubina y otros compuestos (incluidos los fármacos) 13 .…”

Section: Metabolismo (Biotransformación)unclassified

Farmacocinética de medicamentos de uso pediátrico, visión actual

B³

et al. 2008

Rev. chil. pediatr.

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Pediatric drugs pharmacokinetics Pharmacokinetics corresponds to the branch of pharmacology that studies the absorption, distribution, biotransformation and excretion of drugs in the body, in order to proportionate a reference line for interpretation of drug concentration in biological fluids, fundamental for clinical therapy. While adult pharmacology has increase greatly, advances in pediatric pharmacology have been poor. Therefore, drug prescription in children is essentially empirical on the basis of an inmature organism. An effective, secure and rational pediatric pharmacology requires exhaustive knowledgement of the developmental changes in relation to absorption, distribution, metabolism and excretion affecting pharmacokinetics parameters; therefore, the effective dose. This review describes fundamental differences between adult and pediatric pharmacokinetics. These differences must be considered when therapeutic strategies develop for newborns and children.

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Cytochrome P-450-Dependent Monooxygenase Activities in Prenatal and Postnatal Human Livers: Comparison of Human Liver 7-Alkoxycoumarin O-Dealkylases with Rat Liver Enzymes

Cited by 12 publications

References 36 publications

Intralobular distribution and quantitation of cytochrome P-450 enzymes in human liver as a function of age

Intralobular distribution and quantitation of cytochrome P-450 enzymes in human liver as a function of age

Developmental Regulation of Codeine Analgesia in the Rat

Farmacocinética de medicamentos de uso pediátrico, visión actual

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