Development of Phenobarbital-Sensitive Control Mechanisms for Uridine Diphosphate Glucuronyltransferase Activity in Chick Embryo Liver

Burchell, Brian; Dutton, Geoffrey J.; Nemeth, Andrew M.

doi:10.1083/jcb.55.2.448

Cited by 35 publications

(39 citation statements)

References 13 publications

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“…Maximal induction in the S16 preparation decreased after 12 DI to 4.76 nmol/min per mg at 17 DI and then increased to 7.71 nmol/min per mg by 20 DI. Similarly,, maximal induction in the microsomal preparations decreased after 14 DI to 8.06 nmol/min per mg at 18 DI and then increased sharply on subsequent days to a maximum of 15.13 nmol/min per mg at 1 day old, a value 9 times higher than 1-day-old controls,(also increased) and [30][31][32][33][34][35][36][37][38][39][40] (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…Ultrastructural studies have shown that the hepatocytes are morphologically fully differentiated by 8 DI and that liver growth prior to 7 DI is due to cell growth and division whereas after 7 DI liver growth is almost solely due to cell division (31,32). One of the major changes in the hepatocytes from 4 to 7 DI is the proliferation of endoplasmic reticulum, and UDP-glucuronyltransferase activity is induced by phenobarbital in raft-cultured 7 DI embryonic liver, an agent that also induces a significant increase in endoplasmic reticulum (31,33 (34) investigated the development of phenobarbital-sensitive control mechanisms in cultured chicken embryo liver. They suggested that the differences in degree and time-course of induction of UDP-glucuronyltransferase in livers from 5-DI and 11-DI chicken embryos were a result of differences in regulatory mechanisms of enzyme induction at the two ages and that these differences reflected developmental changes occurring in ovo.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of basal and induced aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in the chicken embryo in ovo.

Hamilton

Denison

Bloom

1983

Proc. Natl. Acad. Sci. U.S.A.

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The development of the hepatic microsomal mixed-function oxidase system was studied to determine the basal level of embryonic enzyme activity and the inducibility of this system throughout growth and differentiation. Chicken embryo livers were assayed for basal and inducible hepatic aryl hydrocarbon hydroxylase (AHHase; designated elsewhere as AHH) activity from the first appearance of the liver as a discrete organ at 5 days of incubation (DI) through day 10 after hatching. In addition, wholeembryo and viscera preparations were assayed at 3 and 4 DI. Basal AHHase activity was equal to or greater than adult levels from 3 DI through hatching in all preparations (approximately 0.3-0.5 nmol/min per mg). A 3-fold increase in basal activity above adult values occurred at hatching. The onset of inducibility in chicken embryo liver between 5 and 6 DI was concomitant with hepatocyte differentiation. A developmental profile of 24-hr 3,4,3',4'-tetrachlorobiphenyl-induced AHHase activity showed 15-to 30-fold induction over controls from 7 DI through day 10 after hatching, with a maxmum of 15 nmol/min per mg at 14 DI and day 1 after hatching, a specific activity >50% greater than maximal induction in the adult. Embryonic AHHase activity was also induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, 3-naphthoflavone, and sodium phenobarbital. Induction kinetics throughout embryonic development were similar to those reported for the adult chicken and other animals. These findings demonstrate development of a mixed-function oxidase system in very early embryogenesis and then in the liver as it differentiates. Liver AHHase activity is inducible throughout development and perinatally but such activity is under strict developmental regulation. The chicken embryo has adult levels of AHHase activity which would be sufficient to achieve metabolic activation of promutagens /carcinogens before and after hepatocyte differentiation.The chicken embryo is a sensitive indicator of the teratogenic (1) and mutagenic (2) capacity of xenobiotics. Since its development as the first in vivo sister chromatid exchange (SCE) assay (3), it has been used to screen more than 50 compounds for mutagenic activity, including both direct-and indirect-acting compounds (4, 5). The induction of SCEs at 3 days of incubation (DI) by compounds known to require activation to mutagenic metabolites indicates the presence of a xenobiotic-metabolizing system very early in chicken embryo development (4, 5). Furthermore, there was an increase in the frequency of SCEs at 6 DI from the same dose of an indirect-acting mutagen/carcinogen compared to the SCE frequency at 3 DI, in spite of a 17-fold increase in embryo weight, whereas the same dose of direct-acting mutagen at 6 DI as at 3 DI caused a decrease in SCEs in the older embryo (6). This differential response between 3 DI and 6 DI potentially could be explained by either an increase in basal enzyme levels or an increased inducibility of xenobiotic-metabolizing enzymes.Drummond et aL (7) report...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Development of basal and induced aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in the chicken embryo in ovo.

Hamilton

Denison

Bloom

1983

Proc. Natl. Acad. Sci. U.S.A.

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“…THe conclusion was that developmental onset of glucuronidation appears to be regulated by increased amounts of UDPGT (19,28). This idea was further reinforced by the ability of protein synthesis inhibitors to prevent the developmental onset of activity (29). However, the situation is complicated by the fact that yolk added to the tissue culture delays the development of glucuronyltransferase (19).…”

Section: Animalsmentioning

confidence: 99%

Perinatal Development of Conjugative Enzyme Systems

Lucier¹

1976

Environmental Health Perspectives

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The problems and priorities involved in studying the role of conjugagive enzymes in developmental pharmacology are discussed and evaluated. The relative rates of UDP glucuronyltransfererase and P-glucuronidase were studied during perinatal development in hepatic and extrahepatic tissues to determine the net balance of glucuronidation or deglucuronidation at different developmental stages. In general, deglucuronidation predominated over glucuronidation in fetal tissues whereas the converse was evident in adults. 2,3,7,8-Tetrachlorodibenzop-dioxin I TCDD ), an extremely toxic contaminant of some organochlorine compounds, was shown to be a potent inducer of some hepatic and extrahepatic drug-metabolizing enzymes. TCDD, administered during gestation, induced the postnatal activities of p-nitrophenol glucuronyltransferase and benzpyrene hydroxylase in rats. Foster mother experiments revealed that the postnatal induction was caused primarily by newborn exposure to TCDD in the mother's milk. Tissue distribution experiments with TCDD-'4C confirmed these findings. Although TCDD induced nonsteroid glucuronidation, no significant effects were evident on the postnatal development of steroid glucuronidation. The synthetic estrogen diethylstilbestrol IDES Iis metabolized primarily by glucuronidation. The postnatal development of DES glucuronidation, like the steroid pathway, was not affected by gestational TCDD treatment. The fetal distribution of DES and DES-glucuronide, at different stages of development, correlated well with the perinatal development of steroid glucuronyltransferase activity.

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“…It also reduces or controls seizures or convulsions, except for absence (petit mal) seizures. Generic Phenobarbital oral elixir is available containing a high amount of alcohol which can increase possible unpleasant Effects 3,4 . Literature survey further revealed that the analytical method available for determination of drug phenobarbitone by modified conductometric analysis .…”

Section: Figure 1: Structure Of Phenobarbitonementioning

confidence: 99%

Untitled

2013

IJPSR

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A sensitive, selective, precise and stability indicating high performance thin layer chromatographic method of analysis of Phenobarbitone both as a bulk drug and in formulations was developed and validated in pharmaceutical dosage form. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of dichloromethane: ethyl acetate: glacial acetic acid (9.5:0.5:0.1 v/v/v/v). This system was found to give compact spots for Phenobarbitone (Rf value of 0.70). Phenobarbitone was subjected to acid and alkali hydrolysis, oxidation, photodegradation and dry heat treatment also the degraded products were well separated from the pure drug. Densitometric analysis of Phenobarbitone was carried out in the absorbance mode at 244 nm. The linear regression data for the calibration plots showed good linear relationship with r 2 =/0.998/ in the concentration range of 200-/600 ng/band. The method was validated for precision, accuracy, ruggedness and recovery. The limits of detection and quantitation were 5.82 and 14.60 ng per spot, respectively. The drug undergoes degradation under acidic, alkaline conditions, oxidation and dry heat treatment. Peaks of degraded product were resolved from the standard drug with significantly different Rf values. This indicates that the drug is susceptible to acid hydrolysis/alkaline hydrolysis, oxidation, dry heat degradation. Statistical analysis proves that the method is reproducible and selective for the estimation of the said drug. As the method could effectively separate the drug from its degradation products, it can be employed as a stability indicating one.

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Development of Phenobarbital-Sensitive Control Mechanisms for Uridine Diphosphate Glucuronyltransferase Activity in Chick Embryo Liver

Cited by 35 publications

References 13 publications

Development of basal and induced aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in the chicken embryo in ovo.

Development of basal and induced aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in the chicken embryo in ovo.

Perinatal Development of Conjugative Enzyme Systems

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