scholarly journals Drug-induced accumulation of uroporphyrin in chicken hepatocyte cultures. Structural requirements for the effect and role of exogenous iron

1984 ◽  
Vol 224 (3) ◽  
pp. 769-777 ◽  
Author(s):  
A Ferioli ◽  
C Harvey ◽  
F De Matteis

The ability of drugs to cause uroporphyria in hepatocytes from 17-day-old chick embryos has been investigated and the response of the cells in culture compared with that of the intact liver of the embryos in ovo. In this chick-embryo system, drugs that cause accumulation of uroporphyrin within 19-24 h can only do so in culture; in contrast, 2-allyl-2-isopropylacetamide and 3,5-diethoxycarbonyl-1,4-dihydrocollidine, which stimulate production of protoporphyrin, are effective both in culture and in ovo. A role of exogenous iron in worsening drug-induced uroporphyria was demonstrated in cultures of hepatocytes; iron also caused preferential accumulation of uroporphyrin from added 5-aminolaevulinate in the absence of a porphyrogenic chemical. Uroporphyria was induced in cultures of hepatocytes by drugs of widely different structures, suggesting that the primary molecular target with which they interact may be relatively aspecific in its binding characteristics. These results are briefly discussed, and two alternative hypotheses for the drug-induced effect in uroporphyrinogen metabolism are considered.

1981 ◽  
Vol 198 (2) ◽  
pp. 321-329 ◽  
Author(s):  
U Giger ◽  
U A Meyer

The role of haem synthesis during induction of hepatic cytochrome P-450 haemoproteins was studied in chick embryo in ovo and in chick embryos hepatocytes cultured under chemically defined conditions. 1. Phenobarbitone caused a prompt increase in the activity of 5-aminolaevulinate synthase, the rate-limiting enzyme of haem biosynthesis, and in the concentration of cytochrome P-450. This induction response occurred without measurable initial destruction of the haem moiety of cytochrome P-450. 2. When intracellular haem availability was enhanced by exogenous haem or 5-aminolaevulinate, phenobarbitone-medicated induction of cytochrome P-450 was not affected in spite of the well known repression of 5-aminolaevulinate synthase by haem. These data are consistent with the concept that haem does not regulate the synthesis of cytochrome P-450 haemoproteins. 3. Acetate inhibited haem biosynthesis at the level of 5-aminolaevulinate formation. When intracellular haem availability was diminished by treatment with acetate, phenobarbitone-medicated induction was decreased. 4. This inhibitory effect of acetate on cytochrome P-450 induction was reversed by exogenous haem or its precursor 5-aminolaevulinate. These data suggest that inhibition of haem biosynthesis does not decrease synthesis of apo-cytochrome P-450. Moreover, they indicate that exogenous haem can be incorporated into newly formed aop-cytochrome P-450.


Development ◽  
1969 ◽  
Vol 22 (3) ◽  
pp. 349-371
Author(s):  
P. D. F. Murray ◽  
Daniel B. Drachman

Skeletal muscle contractions are necessary during embryonic life for the normal development of joints. The general features of joint development in immobile limbs were first studied with the techniques of grafting and organ culture. (Murray, 1926; Murray & Selby, 1930; Fell, 1925; Fell & Canti, 1934; Hamburger & Waugh, 1940; Lelkes, 1958). However, these methods of necessity entail a drastic alteration in the environment of the developing articulations, which may result in gross distortions of the skeletal structures themselves. More recently, neuromuscular blocking agents have been used to produce paralysis of chick embryos in ovo. When administered intravenously, these pharmacological substances produce profound paralysis, which may be continued for prolonged periods during embryonic development (Drachman & Coulombre, 1962a, b). Drachman & Sokoloff (1966) have analyzed the primary development of the knee, ankle and toe joints of the chick embryo by the use of these methods.


2013 ◽  
Vol 304 (6) ◽  
pp. H895-H902 ◽  
Author(s):  
Radka Kockova ◽  
Jarmila Svatunkova ◽  
Jiri Novotny ◽  
Lucie Hejnova ◽  
Bohuslav Ostadal ◽  
...  

A significant increase in cardiovascular medication use during pregnancy occurred in recent years. Only limited evidence on safety profiles is available, and little is known about the mechanisms of adverse effect on the fetus. We hypothesized that drug-induced bradycardia is the leading mechanism of developmental toxicity. Embryotoxicity was tested in ovo after administration of various doses of metoprolol, carvedilol, or ivabradine. Embryonic day (ED) 4 and 8 chick embryos were studied by video microscopy and ultrasound biomicroscopy ex ovo after intraamniotic injection of the drug for a period of 30 min. Stroke volume was calculated by the Simpson method and prolate ellipsoid formula. Significant dose-dependent mortality was achieved in embryos injected with carvedilol and ivabradine. In ED4 embryos, metoprolol, carvedilol, and ivabradine reduced the heart rate by 33%, 27%, and 55%, respectively, compared with controls (6%). In ED8 embryos this effect was more pronounced with a heart rate reduction by 71%, 54%, and 53%, respectively (controls, 36%). Cardiac output decreased in all tested groups but only proved significant in the metoprolol group in ED8 embryos. The number of β-adrenergic receptors showed a downward tendency during embryonic development. A negative chronotropic effect of metoprolol, carvedilol, and ivabradine was increasingly pronounced with embryonic maturity despite a downward trend in the number of β-adrenergic receptors. This effect was associated with reduced cardiac output in chick embryos, probably leading to premature death. Although standard doses of these drugs appear relatively safe, high doses have a potentially adverse effect on the fetus through reduced heart rate.


1973 ◽  
Vol 51 (9) ◽  
pp. 700-704 ◽  
Author(s):  
Hillel Taub ◽  
G. S. Marks

Propanidid, an ultra short-acting non-barbiturate anesthetic containing an ester group, induces δ-aminolevulinic acid (ALA)-synthetase and porphyrin accumulation in 17-day-old chick embryo liver. The potency and duration of action of propanidid in inducing ALA-synthetase activity and porphyrin accumulation was markedly increased when administered to chick embryos which had been pretreated with bis-[p-nitrophenyl] phosphate, an inhibitor of liver carboxylesterase.


Development ◽  
1980 ◽  
Vol 57 (1) ◽  
pp. 37-49
Author(s):  
Robert Minkoff

Variation in rates of cell proliferation along the long axis of the maxillary process, within the lateral nasal process and in the zone of attachment between these structures was analyzed employing DNA labeling indices. Chick embryos were labeled with [3H]thymidine for 1 h and processed for histology and autoradiography. The percentage of labeled mesenchymal cellswas determined in delineated areas. Analysis of labeling indices indicated that rates of cell proliferation varied withineach of the facial processes. Regions where rates of proliferation were maintained at elevated levels were the boundary areas of the facial processes (e.g. the anterior tip of the maxillary process) and the zones of attachment between the facial processes (e.g. between the maxillary process and the lateral nasal process). Despite the presence of elevated rates of proliferation in selected regions within the facial processes, however, the percentage of labeled cells in all areas declined with advancing developmental age. These findings support the hypothesis, proposed by Streeter and Patten, that the ‘merging’ of adjacent facial primordia, such as the maxillary and lateral nasal processes, is accomplished by elevated rates of cell proliferation within the zones of attachment compared to the rates of proliferation in adjacent regions.


2015 ◽  
Vol 26 (5) ◽  
pp. 978-992 ◽  
Author(s):  
Guang Wang ◽  
Yan Li ◽  
Xiao-Yu Wang ◽  
Manli Chuai ◽  
John Yeuk-Hon Chan ◽  
...  

This is the first study of the role of BRE in embryonic development using early chick embryos. BRE is expressed in the developing neural tube, neural crest cells, and somites. BRE thus plays an important role in regulating neurogenesis and indirectly somitogenesis during early chick embryo development.


Author(s):  
Margaret H. Sanderson ◽  
S. Phyllis Steamer

The chick embryo exposed to lethal doses of ionizing radiations develops a fatal circulatory failure within a few hours. This report describes the blood vessels of the area pellucida (a part of the extra-embryonic membranes of the chick embryo) and the effect of 250 kVp x-radiation upon them.Three-day chick embryos, x-irradiated in ovo with 1000-1200 R, were fixed 1-2 hours after exposure. The area pellucida is a multi-layered membrane consisting of ectoderm, somatic and splanchnic mesoderm, and endoderm (Fig. 1). The vascular system arises from the splanchnic mesoderm. The walls of small and medium-sized vessels are composed of endothelial cells, an occasional pericyte and processes of adjacent mesenchyme cells. Types of vessels cannot be distinguished at this stage of development; a basement membrane is seen only in isolated areas. The wall appears double or triple-layered, but the endothelium is frequently less than 0.1 micron thick (Fig. 2). Endothelial cells contain a large complement of polyribosomes, mitochondria, rough and smooth endoplasmic reticulum, a Golgi complex, pinocytotic vesicles and several kinds of inclusion bodies. The nucleus has a well-defined nucleolus.


Development ◽  
1981 ◽  
Vol 61 (1) ◽  
pp. 175-190
Author(s):  
K. Palén ◽  
L. Thörneby

Chick embryos were treated in ovo and in vitro with L-phenylalanine from the intermediate streak stage (Hamburger & Hamilton stage 3, 12–13 h of incubation) to the 7-somite stage (H & H stage 9, 29–33 h of incubation). Treatment in ovo resulted in a large number of embryos developing somite blocks, i.e. imperfectly segmented somites. In embryos treated at an early developmental stage (12–21 h of incubation), the blocks of unsegmented somite mesoderm occurred mostly in the somite pairs 1–5, whereas treatment that began at a later stage (24–30 h of incubation) caused blocks in the somite pairs 5–10, i.e. the appearance of blocks of unsegmented somite mesoderm is correlated in time with the onset of the treatment. No difference regarding mitotic indices could be distinguished between normally segmented somites and blocks of unsegmented somite mesoderm. Autoradiography based on tritiated L-phenylalanine showed no regional differences in labelling of the chick embryo body. Electronmicroscopical observations indicate a slightly suppressed formation of microvilli in the cells of the unsegmented mesoderm blocks compared with cells in normally segmented somites. The observed disturbances are probably caused by a suppressed yolk granule decomposition in the developing somite cells. The experiments in vitro support the findings in the in ovo material; at the same time, they reveal an unexpectedly slow diffusion of L-phenylalanine through the vitelline membrane.


1956 ◽  
Vol 103 (6) ◽  
pp. 777-797 ◽  
Author(s):  
Oscar C. Liu ◽  
Kurt Paucker ◽  
Werner Henle

Certain aspects of the formation of non-infectious hemagglutinins (NIHA) in the chick embryo infected with influenza virus have been analyzed. It was shown by the use of combined in ovo-deembryonation technics that little or no NIHA is released following infection with small doses of standard virus during the most active and constant growth periods of the virus extending to about the 36th hour of incubation in spite of the fact that multiple infection of cells must have taken place in the latter half of that period. A slight decrease in the ID50/HA ratios of the yields obtained after the 36th hour, coinciding with the falling off of virus production and release may possibly be explained in terms of inactivation of completed virus or leakage of as yet incompleted virus from damaged cells. Exposure of the entodermal cells of the allantois of eggs deembryonated shortiy after injection of saturation or near saturation inocula of standard seed to large quantities of infectious virus added to the media at various times after infection and not extending over more than 2 hours resulted in a decrease of the ID50/HA ratios of the progenies only during the first 2 or possibly 4 hours after the primary inoculation. Later addition did not influence the yields. As discussed, such sudden and heavy exposures of cells are not expected to occur during the infectious process induced by small inocula of standard seed. The possible role of destruction of cell receptors in NIHA production has been analyzed in several ways. The addition of receptor-destroying enzyme (RDE) to the media of deembryonated eggs after near saturation inocula of standard seeds, if anything, increased the ID50/HA ratios of the progenies, and that only when added during the first few hours following infection, presumably by reducing the changes for high multiplicity of infection of cells. In contrast, ultraviolet-inactivated virus, which retains its enzymatic activity, lowered, if anything, the ID50/HA ratios of the progenies, when present in the media of deembryonated eggs from the 2nd to 4th or possibly 6th hour after infection. Excessive amounts of irradiated virus may still cause some degree of interference under these conditions. Later addition of irradiated viruses were without effect with respect to NIHA production or interference. In attempts to alter the cell receptors prior to infection by potassium periodate (KIO4), it was noted that the addition of glycerol led to the appearance and partial retention for at least 24 hours of substances in the allantoic fluids which were capable of inactivating considerable proportions of standard virus. These data indicate that destruction of external cell receptors plays little if any role in NIHA production. The implications of these findings are discussed.


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