scholarly journals Precocious development of glucuronidating and hydroxylating enzymes in chick embryos treated with pituitary grafts

1975 ◽  
Vol 152 (2) ◽  
pp. 325-331 ◽  
Author(s):  
Graham J. Wishart ◽  
Geoffrey J. Dutton
Keyword(s):  
Chorioallantoic Membrane ◽  
Pars Distalis ◽  
Liver And Kidney ◽  
Embryo Liver ◽  
First Time ◽  
Cytochrome P 450 ◽  
Isolated Liver ◽  
Precocious Development ◽  
Nadph Cytochrome C Reductase

1. Initiation of precocious development of UDP-glucuronyltransferase by an endogenous factor is reported for the first time. 2. This development occurs in chick embryo liver and kidney after grafting of the cephalic lobe of chicken pars-distalis pituitary tissue on to the chorioallantoic membrane, and in liver results in a rise in the enzyme activity from virtually zero to ‘adult’ values. Aniline hydroxylase also precociously develops in the liver of grafted embryos, its activity rising from one-third to the full adult value. Specific activities of glucose 6-phosphatase, cytochrome P-450 and NADPH–cytochrome c reductase did not significantly change. 3. The response of the transferase does not require the presence of host pituitary gland nor, apart from 1 day's necessary initiation, the presence of the graft itself. 4. The host becomes competent to respond on the 14th day of incubation; response continues for at least 3 days after removal of the graft, and for 2 days in the isolated liver. Grafting of embryonic pars distalis younger than 17 days does not evoke a response in the host liver. 5. Secretion of the pituitary factor increases suddenly some 24–48h before the naturally developing surge in liver UDP-glucuronyltransferase activity and may be responsible for initiating this rise in vivo. 6. The factor is probably not a growth or luteinizing hormone; its nature and the likelihood of a secondary hormone acting directly on the liver are discussed.

scholarly journals Phenylhydrazine-mediated induction of haem oxygenase activity in rat liver and kidney and development of hyperbilirubinaemia. Inhibition by zinc-protoporphyrin

1984 ◽  
Vol 217 (2) ◽  
pp. 409-417 ◽  
Author(s):  
M D Maines ◽  
J C Veltman
Keyword(s):  
Rat Liver ◽  
Zinc Protoporphyrin ◽  
Serum Total Bilirubin ◽  
Potent Inducer ◽  
Oxygenase Activity ◽  
Liver And Kidney ◽  
Haem Oxygenase ◽  
Cytochrome P 450

Phenylhydrazine was found to be a potent inducer of microsomal haem oxygenase activity in rat liver and kidney, but not in spleen. The phenylhydrazine-mediated increase in haem oxygenase activity was time-dependent. Maximum activity was attained 12h after treatment in the liver, and 24h after treatment in the kidney. The increases in the activity of haem oxygenase in the liver and the kidney could be inhibited by cycloheximide. Furthermore, the increases could not be elicited by the treatment of microsomal preparations in vitro with phenylhydrazine. In consonance with the increased haem oxygenase activity, a marked increase (16-fold) was observed in the serum total bilirubin concentration in phenylhydrazine-treated rats. The mechanism of haem degradation promoted by phenylhydrazine in vivo appears to differ from that in vitro; only in the former case is bilirubin formed as the end-product of haem degradation. When rats were given zinc-protoporphyrin (40 mumol/kg) 12h before and after phenylhydrazine treatment, the phenylhydrazine-mediated increases in haem oxygenase activity in the liver and the kidney were effectively blocked. Treatment of rats in vivo with the metalloporphyrin also inhibited the activity of splenic haem oxygenase, and promoted a major decrease in the serum bilirubin levels. In phenylhydrazine-treated animals, the microsomal content of cytochrome P-450 was significantly decreased in the absence of a decrease in the microsomal haem concentration. The decrease in cytochrome P-450 content was accompanied by an increased absorption in the 420nm region of the reduced CO-difference spectrum, suggesting the conversion of the cytochrome to an inactive form. The marked depletion of cellular glutathione levels suggests that this conversion may be related to the action of active intermediates and free radicals formed in the course of the interaction of phenylhydrazine with the haem moiety of cytochrome P-450.

scholarly journals Precocious development of uridine diphosphate glucuronosyltransferase activity during organ culture of foetal rat liver in the presence of glucocorticoids

1977 ◽  
Vol 166 (2) ◽  
pp. 249-253 ◽  
Author(s):  
G J Wishart ◽  
M A Goheer ◽  
J E A Leakey ◽  
G J Dutton
Keyword(s):  
Rat Liver ◽  
Defined Medium ◽  
Transferase Activity ◽  
Uridine Diphosphate ◽  
Chemically Defined Medium ◽  
Foetal Rat ◽  
First Time ◽  
Precocious Development ◽  
Stimulation Of

1. Precocious development of mammalian UDP-glucuronosyltransferase (EC 2.4.1.1.7) induced by endogenous compounds of known chemical composition is reported for the first time. 2. This development occurs in cultured explants of foetal rat liver when exposed to corticosteroids possessing a pregn-4′-ene structure and a hydroxy or an oxo group at C-11. 3. Explants from 14-day foetuses cultured for 3 days in a chemically defined medium containing dexamethasone exhibited transferase activities towards o-aminophenol within adult male values. Those liver transferase activities attained in utero by 17 days were still negligible. 4. Evidence from several approaches indicated that the explants required glucocorticoids for expression of the transferase, not for maintenance of viability. 5. Glucocorticoid-dependent stimulation of transferase activity required incorporation of L-[14C]leucine into protein, as judged from the pulsing of cultures with cycloheximide. 6. The relevance of these culture experiments to the situation in vivo is discussed.

scholarly journals Visualizing Drug Efficacy In Vivo

2005 ◽  
Vol 4 (2) ◽  
pp. 153535002005051 ◽  
Author(s):  
Weisheng Zhang ◽  
Min Chen ◽  
David B. West ◽  
Anthony F. Purchio
Keyword(s):  
Enzyme Activity ◽  
Drug Metabolism ◽  
Drug Effects ◽  
Study Drug ◽  
Drug Efficacy ◽  
Biochemical Assays ◽  
Metabolism Enzymes ◽  
First Time ◽  
Cytochrome P 450

Many enzymes are therapeutic targets for drug discovery, whereas other enzymes are important for understanding drug metabolism and pharmacokinetics during compound testing in animals. Testing of drug efficacy and metabolism in an animal model requires the measurement of disease endpoints as well as assays of enzyme activity in specific tissues at selected time points during treatment. This requires the removal of tissue and biochemical assays. Techniques to noninvasively assess drug effects on enzyme activity using imaging technology would facilitate understanding of drug efficacy, pharmacokinetics, and drug metabolism. Using a commercially available cytochrome P−450 3A substrate whose oxidized product is a luciferase substrate, we show for the first time that cytochrome P−450 enzyme activity can be measured in vivo in real time by bioluminescent imaging. This imaging approach could be applicable to study drug effects on therapeutic target enzymes, as well as drug metabolism enzymes.

Integrating genetics and genomics to identify new leads for the control ofEimeriaspp.

Parasitology ◽  
2004 ◽  
Vol 128 (S1) ◽  
pp. S33-S42 ◽  
Author(s):  
M. W. SHIRLEY ◽  
D. BLAKE ◽  
S. E. WHITE ◽  
R. SHERIFF ◽  
A. L. SMITH
Keyword(s):  
Protective Immunity ◽  
Wide Spectrum ◽  
Chorioallantoic Membrane ◽  
In Ovo ◽  
Selection Procedures ◽  
Immune Mediated ◽  
The Face ◽  
The Many ◽  
Precocious Development

Eimerian parasites display a biologically interesting range of phenotypic variation. In addition to a wide spectrum of drug-resistance phenotypes that are expressed similarly by many other parasites, theEimeriaspp. present some unique phenotypes. For example, unique lines ofEimeriaspp. include those selected for growth in the chorioallantoic membrane of the embryonating hens egg or for faster growth (precocious development) in the mature host. The many laboratory-derived egg-adapted or precocious lines also share a phenotype of a marked attenuation of virulence, the basis of which is different as a consequence of thein ovoorin vivoselection procedures used. Of current interest is the fact that some wild-type populations ofEimeria maximaare characterized by an ability to induce protective immunity that is strain-specific. The molecular basis of phenotypes that defineEimeriaspp. is now increasingly amenable to investigation, both through technical improvements in genetic linkage studies and the availability of a comprehensive genome sequence for the caecal parasiteE. tenella. The most exciting phenotype in the context of vaccination and the development of new vaccines is the trait of strain-specific immunity associated withE. maxima. Recent work in this laboratory has shown that infection of two inbred lines of White Leghorn chickens with the W strain ofE. maximaleads to complete protection to challenge with the homologous parasite, but to complete escape of the heterologous H strain, i.e. the W strain induces an exquisitely strain-specific protective immune response with respect to the H strain. This dichotomy of survival in the face of immune-mediated killing has been examined further and, notably, mating between a drug-resistant W strain and a drug-sensitive H strain leads to recombination between the genetic loci responsible for the specificity of protective immunity and resistance to the anticoccidial drug robenidine. Such a finding opens the way forward for genetic mapping of the loci responsible for the induction of protective immunity and integration with the genome sequencing efforts.

scholarly journals Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miguel Angel Merlos Rodrigo ◽  
Hana Michalkova ◽  
Vladislav Strmiska ◽  
Berta Casar ◽  
Piero Crespo ◽  
...  
Keyword(s):  
Cisplatin Resistance ◽  
Neuroblastoma Cells ◽  
Chorioallantoic Membrane ◽  
In Vivo Model ◽  
Chick Chorioallantoic Membrane ◽  
High Level ◽  
Cisplatin Chemoresistance ◽  
The Impact ◽  
First Time

AbstractMetallothionein-3 has poorly characterized functions in neuroblastoma. Cisplatin-based chemotherapy is a major regimen to treat neuroblastoma, but its clinical efficacy is limited by chemoresistance. We investigated the impact of human metallothionein-3 (hMT3) up-regulation in neuroblastoma cells and the mechanisms underlying the cisplatin-resistance. We confirmed the cisplatin-metallothionein complex formation using mass spectrometry. Overexpression of hMT3 decreased the sensitivity of neuroblastoma UKF-NB-4 cells to cisplatin. We report, for the first time, cisplatin-sensitive human UKF-NB-4 cells remodelled into cisplatin-resistant cells via high and constitutive hMT3 expression in an in vivo model using chick chorioallantoic membrane assay. Comparative proteomic analysis demonstrated that several biological pathways related to apoptosis, transport, proteasome, and cellular stress were involved in cisplatin-resistance in hMT3 overexpressing UKF-NB-4 cells. Overall, our data confirmed that up-regulation of hMT3 positively correlated with increased cisplatin-chemoresistance in neuroblastoma, and a high level of hMT3 could be one of the causes of frequent tumour relapses.

scholarly journals Ameliorative Effects of Cholestyramine and Oxihumate on Aflatoxicosis in Broiler Chickens

2021 ◽  
Vol 41 (01) ◽  
pp. 51-56
Author(s):  
Abdel Moneim A Ali
Keyword(s):  
Dose Rate ◽  
Broiler Chickens ◽  
Basal Diet ◽  
Beneficial Effects ◽  
Ameliorative Effect ◽  
Liver And Kidney ◽  
Group A ◽  
Group B ◽  
First Time

Aflatoxin B1 (AFB1) is widely available mycotoxin that is secreted by certain types of Aspergilli. In this research the ameliorative efficacy of two mycotoxin binders in broilers was evaluated; cholestyramine which was used for the first time in the poultry and oxihumate. A total of 64 one-day-old chicks were divided into four equal groups: birds of group A, B & C were fed on AFB1 contaminated diet at a rate of 2 ppm for 36 days either alone, with cholestyramine at a dose rate of 340µg/kg ration or with oxihumate at a dose rate of 3.5g/kg ration. Group D was kept as control with basal diet of neither toxin nor drug treatment. Morality was highest and the lesions of AFB1 intoxication were pronounced among birds of group A with marked degenerative and necrotic changes in different examined organs. Variable degrees of ameliorative effects of AFB-induced toxic lesions were observed in both treated groups (group B & C) with beneficial effects for cholestyramine. Mild expression of the apoptosis-related marker (p53) was encountered in group B and C relative to AFB1 intoxicated group. Aflatoxin residues were significantly reduced in the bird liver and kidney tissues in the instance of the two antimycotoxin binders. It could be concluded that both cholestyramine and oxihumate have an ameliorative effect for controlling aflatoxicosis with the superiority of cholestyramine in its protective effect. This the first in vivo trail to use cholestyramine as anti-AFB1 agent in poultry

Growth hormone depresses ethylmorphine demethylase activity: correlation with decreased levels of fast-turnover cytochrome P-450 in hypophysectomized female rats

1988 ◽  
Vol 66 (7) ◽  
pp. 868-872
Author(s):  
Birgit M. Vockentanz ◽  
Bruce B. Virgo
Keyword(s):  
Growth Hormone ◽  
Cytochrome C ◽  
Female Rats ◽  
Monooxygenase System ◽  
Demethylase Activity ◽  
Hepatic Monooxygenase ◽  
Cytochrome P 450 ◽  
Slow Turnover ◽  
Nadph Cytochrome C Reductase

The hepatic monooxygenase system was studied in hypophysectomized female rats infused for 5 days with ovine growth hormone (GH). At 7.5 μg∙h−1 GH decreased the total cytochrome P-450 by 16%; at 10 μg∙h−1 it reduced both cytochrome P-450 (31%) and the activity of ethylmorphine demethylase (31%). GH did not alter the activities of NADPH cytochrome c reductase or aniline hydroxylase. The lower GH dose decreased the amount of fast- and slow-turnover P-450 by 11 and 38%, respectively, while the higher dose decreased both by 49%. The loss of demethylase activity therefore correlates with the loss of fast-tumover P-450. This component is relatively more abundant in the female (fast: slow turnover of 4.3) than the male (fast: slow turnover of 2.5). GH did not affect the half-lives of the P-450 components, suggesting that it decreases their synthesis. The P-450 concentration in microsomes from GH-treated animals did not increase after incubation with hemin, suggesting that in vivo the hormone does not lower P-450 synthesis via depression of heme. Puromycin mimicked the effect of GH and when given with the hormone their effects on the P-450 levels were multiplicative (p < 0.05), suggesting different modes of action and that GH does not decrease P-450 by acting at translation.

scholarly journals Metal ion interactions in the control of haem oxygenase induction in liver and kidney

1980 ◽  
Vol 192 (2) ◽  
pp. 637-648 ◽  
Author(s):  
G S Drummond ◽  
A Kappas
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Simultaneous Administration ◽  
Ion Interactions ◽  
Liver And Kidney ◽  
Demethylase Activity ◽  
Haem Oxygenase ◽  
Metal Ion Interactions ◽  
Cytochrome P 450

Mn2+ and Zn2+ exhibit a striking ability to block the induction by Sn2+ and Ni2+ of haem oxygenase (EC 1.14.99.3) in kidney. The blocking effects of Mn2+ and Zn2+ were found to be greatest on simultaneous administration, time-dependent when administered up to 8 h before the inducing metal ions, and ineffective when administered as little as 10 min after the inducing metal ions. The decreases in cytochrome P-450 and haem contents and the sequential changes in delta-aminolaevulinate synthase (EC 2.3.1.37) activity that occur concomitant with haem oxygenase induction were largely eliminated with simultaneous or prior treatment with Mn2+ or Zn2+, but not when Mn2+ or Zn2+ was administered after Sn2+ or Ni2+. Mn2+ and Zn2+ did not increase the catabolism of the enzyme in vivo. Zn2+ on simultaneous administration was also able substantially to block the induction of haem oxygenase by Co2+, Cd2+ and Ni2+ in liver. The Zn2+ blockade of Cd2+ induction was examined in detail, and prior or simultaneous administration of Zn2+ was found to be effective in blocking the induction of haem oxygenase and the concomitant decreases in cytochrome P-450 and haem contents, ethylmorphine demethylase activity and the sequential changes in delta-aminolaevulinate synthase activity. Zn2+ administration 10 min or more after Cd2+ was ineffective in preventing the occurrence of these perturbations in haem metabolism. These findings describe a new and striking biological property of Mn2+ and Zn2+, and indicate the existence of significant metal ion interactions in the control of haem metabolism.

Progesterone C21 hydroxylation and steroid carboxylic acid biosynthesis in the rabbit. In vitro studies with endocrine, metabolic, and potential target tissues

1983 ◽  
Vol 61 (7) ◽  
pp. 722-730 ◽  
Author(s):  
I. R. Senciall ◽  
G. Bullock ◽  
S. Rahal
Keyword(s):  
Cytochrome C ◽  
Liver Microsomes ◽  
Acid Synthesis ◽  
Rabbit Kidney ◽  
Liver And Kidney ◽  
Kidney Microsomes ◽  
Intraspecies Variability ◽  
First Time ◽  
Cytochrome P 450

Progesterone C21-hydroxylase activity has been demonstrated with rabbit kidney microsomes for the first time and the formation of 21-hydroxy-4-pregnen-3,20-dione (DOC) by rabbit liver and kidney microsomes has been quantitated. Considerable intraspecies variability in enzyme activity occurred with both tissues. The liver enzyme (Vmax = 1.28–38.0 nmol/mg protein per 30 min of incubation) was significantly more active than the kidney enzyme (Vmax = 0.028–0.28 nmol/mg protein per 30 min of incubation). Apparent KM values were 1.39 and 0.8 μM, respectively. Cytochrome c (10−5 M), potassium ferricyanide (10−3 M), and 2-methyl-1,2-di-3-pyridyl-1-propanone (metyrapone; 10−3 M) were strongly inhibitory with both tissues, whereas the liver microsomal system was less sensitive than the kidney to CO–air (90:10 v/v) inhibition. Metabolism of [14C]DOC to 4-pregnen-3,20-dione-21-oic (pregnenoic) and 4-androsten-3-one-17β-carboxylic (etienic) acids by liver microsomes and adrenal and ovary homogenates was differentially affected by several factors. CO–air (90:10 v/v), cytochrome c (10−5 M), and metyrapone (10−3 M) inhibited pregnenoic acid synthesis to a greater extent than etienic acid. Sodium cyanide had a stimulatory effect on the synthesis of pregnenoic acid by the liver but less consistent effects with other tissues. These results suggest that one or more cytochrome P-450 systems may be involved in the oxidation of progesterone through to pregnenoic acid by rabbit tissues.

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