scholarly journals Formation of cytochrome P-450 containing haem or cobalt-protoporphyrin in liver homogenates of rats treated with phenobarbital and allylisopropylacetamide

1984 ◽  
Vol 222 (2) ◽  
pp. 453-462 ◽  
Author(s):  
H L Bonkovsky ◽  
J F Sinclair ◽  
J F Healey ◽  
P R Sinclair ◽  
E L Smith
Keyword(s):  
Polyacrylamide Gel Electrophoresis ◽  
Similar Extent ◽  
Factors Affecting ◽  
Cobalt Protoporphyrin ◽  
Liver Homogenates ◽  
Cytochrome P 450 ◽  
Protein Moiety ◽  
Related Compounds ◽  
Insight Into ◽  
Hepatic Cytochrome

The potent porphyrogen allylisopropylacetamide and related compounds decrease hepatic concentrations of cytochrome P-450. This decrease occurs particularly in phenobarbital-induced cytochrome P-450 and is caused by suicidal breakdown of the haem of cytochrome P-450. Quantitative rocket immunoelectrophoresis showed that the protein moiety of the major phenobarbital-inducible form of hepatic cytochrome P-450 was not diminished up to 1 h, but was markedly decreased (to 43% of that of the phenobarbital-treated control) at 20 h after allylisopropylacetamide treatment. In contrast, the concentration of total cytochrome P-450, measured spectrophotometrically, decreased to 30-40% of the control at both 1 and 20 h after allylisopropylacetamide. Cytochrome P-450-dependent demethylations of ethylmorphine and benzphetamine decreased to a similar extent. When liver homogenates from rats treated with allylisopropylacetamide 1 h before being killed were incubated with haem, functional holocytochrome P-450 could be reconstituted from the apoprotein. Incubation with haem increased spectrophotometrically measurable cytochrome P-450 to 69%, ethylmorphine demethylase to 64% and benzphetamine demethylase to 93% of the activities in rats treated with phenobarbital alone. At 20 h after allylisopropylacetamide treatment, however, little or no reconstitution of cytochrome P-450 occurred after incubation with haem. When liver homogenates were incubated with cobalt and protoporphyrin, and microsomal proteins were then subjected to polyacrylamide-gel electrophoresis, cobalt-protoporphyrin was found specifically associated with proteins of Mr 50 000-53 000. When homogenates from rats given allylisopropylacetamide for 1 h or 20 h were compared, it was found that the extent of this association was higher in livers from the rats containing more apocytochrome P-450, suggesting that cobalt-protoporphyrin had associated with the apocytochrome. The data provide insight into the association of haem with the protein moiety of cytochrome P-450 and factors affecting breakdown of this protein.

scholarly journals Decrease in hepatic cytochrome P-450 by cobalt. Evidence for a role of cobalt protoporphyrin

1982 ◽  
Vol 204 (1) ◽  
pp. 103-109 ◽  
Author(s):  
J F Sinclair ◽  
P R Sinclair ◽  
J F Healey ◽  
E L Smith ◽  
H L Bonkowsky
Keyword(s):  
Chick Embryo ◽  
Gel Electrophoresis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Polyacrylamide Gel ◽  
Cobalt Protoporphyrin ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome

Exposure of cultured chick-embryo hepatocytes to increasing concentrations of CoCl2 in the presence of allylisopropylacetamide results in formation of cobalt protoporphyrin, with a reciprocal decrease in haem and cytochrome P-450. Treatment of rats with CoCl2 (84 mumol/kg) and 5-aminolaevulinate (0.2 mmol/kg) also results in formation of cobalt protoporphyrin and a decrease in cytochrome P-450 in the liver. Hepatic microsomal fractions from rats treated with phenobarbital, CoCl2 and 5-aminolaevulinate were analysed by polyacrylamide gel electrophoresis. Cobalt protoporphyrin was associated mainly with proteins of 50000-53000 mol.wt. The results suggest that the formation of cobalt protoporphyrin occurred at the expense of the synthesis of haem, leading to a decrease in cytochrome P-450. Furthermore, the cobalt protoporphyrin that was formed may itself have been incorporated into apocytochrome P-450.

Hepatic cytochrome P-450 in rats submitted to chronic hypobaric hypoxia

1990 ◽  
Vol 259 (4) ◽  
pp. C654-C659 ◽  
Author(s):  
L. E. Costa
Keyword(s):  
Hypobaric Hypoxia ◽  
Female Rats ◽  
Adaptation To Hypoxia ◽  
Simulated Altitude ◽  
Male And Female Rats ◽  
Group 3 ◽  
Liver Homogenates ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome ◽  
Group 1

Hepatic cytochrome P-450 content in adaptation to hypobaric hypoxia was studied in three groups of rats and in their respective controls at sea level atmospheric pressure. The experimental groups were as follows: 1) young male and female rats submitted to 4,400 m (simulated altitude) for 6-8 mo, 2) the same animal model of group 1 submitted to 5,500 m (simulated altitude) for a subsequent period of 2-3 mo, and 3) adult males exposed to 5,500 m for 35 days. Hypoxia caused a marked polycythemia in all three groups, body weight loss in males of the three groups and at 5,500 m also in females, whereas liver weight was normal in groups 1 and 2 and slightly decreased in group 3. Cytochrome P-450 content measured in microsomal suspensions of groups 1 and 2 was unchanged. In liver homogenates, cytochrome P-450 content was normal at 4,400 m (group 1) and decreased at 5,500 m (groups 2 and 3). Therefore, endoplasmic reticulum mass, calculated as the ratio of cytochrome P-450 in the homogenates and in the isolated microsomes, was unchanged in group 1 (4,400 m) and decreased in group 2 (5,500 m). The content of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, measured in liver homogenates of group 3, were markedly decreased (by 40, 30, and 35%, respectively). Results do not support the hypothesis that an increase in cytochrome P-450 content plays a role in adaptation to hypoxia.

FACTORS AFFECTING THE ACTIVITY OF ALLOXAN IN VITRO

1955 ◽  
Vol 33 (5) ◽  
pp. 780-791 ◽  
Author(s):  
S. J. Klebanoff
Keyword(s):  
Oxygen Uptake ◽  
Succinic Dehydrogenase ◽  
Selective Toxicity ◽  
Factors Affecting ◽  
Stable Factor ◽  
Heat Stable ◽  
Number Of Factors ◽  
Liver Homogenates ◽  
Insight Into

The effect of alloxan on the oxygen uptake and the succinic dehydrogenase activity of rat liver homogenates has been studied in an attempt to gain some insight into the activity of alloxan within the cell. The increased oxygen uptake on the addition of alloxan to liver homogenates was found to be non-enzymatic in nature and to depend on some heat stable factor or factors in the preparation. The ability of reduced glutathione to substitute for the homogenate suggests that this substance may be concerned. It is thought that alloxan is reduced to dialuric acid by a number of factors in the homogenate, and that the increased oxygen uptake results from the spontaneous reoxidation of this latter substance. Experiments with dialuric acid tend to confirm this hypothesis. The inactivation of succinic dehydrogenase by alloxan is greatly influenced by the pH of the solution in which the alloxan is dissolved, as well as by the pH of the enzyme preparation, with acidity increasing and alkalinity decreasing the effect. The progressive nature of the inactivation with time is shown to depend upon the lowering of the pH which is brought about by the addition of alloxan to an unbuffered enzyme mixture. The experimental results are discussed in relation to the possible importance of pH in the selective toxicity of alloxan.

FACTORS AFFECTING THE ACTIVITY OF ALLOXAN IN VITRO

1955 ◽  
Vol 33 (1) ◽  
pp. 780-791
Author(s):  
S. J. Klebanoff
Keyword(s):  
Oxygen Uptake ◽  
Succinic Dehydrogenase ◽  
Selective Toxicity ◽  
Factors Affecting ◽  
Stable Factor ◽  
Heat Stable ◽  
Number Of Factors ◽  
Liver Homogenates ◽  
Insight Into

The effect of alloxan on the oxygen uptake and the succinic dehydrogenase activity of rat liver homogenates has been studied in an attempt to gain some insight into the activity of alloxan within the cell. The increased oxygen uptake on the addition of alloxan to liver homogenates was found to be non-enzymatic in nature and to depend on some heat stable factor or factors in the preparation. The ability of reduced glutathione to substitute for the homogenate suggests that this substance may be concerned. It is thought that alloxan is reduced to dialuric acid by a number of factors in the homogenate, and that the increased oxygen uptake results from the spontaneous reoxidation of this latter substance. Experiments with dialuric acid tend to confirm this hypothesis. The inactivation of succinic dehydrogenase by alloxan is greatly influenced by the pH of the solution in which the alloxan is dissolved, as well as by the pH of the enzyme preparation, with acidity increasing and alkalinity decreasing the effect. The progressive nature of the inactivation with time is shown to depend upon the lowering of the pH which is brought about by the addition of alloxan to an unbuffered enzyme mixture. The experimental results are discussed in relation to the possible importance of pH in the selective toxicity of alloxan.

Possible Interaction of Ranitidine with Phenytoin

1988 ◽  
Vol 22 (12) ◽  
pp. 979-980 ◽  
Author(s):  
Diane Bramhall ◽  
Marc Levine
Keyword(s):  
Steady State ◽  
Animal Studies ◽  
Inhibitory Action ◽  
Clinical Investigation ◽  
State Level ◽  
Steady State Level ◽  
Factors Affecting ◽  
Steady State Serum ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome

Clinical and animal studies have shown that cimetidine and ranitidine can inhibit hepatic cytochrome P-450-mediated metabolism of a variety of other drugs. This occurs to a lesser extent with ranitidine than with cimetidine at doses commonly used to treat gastric acid-related disorders. We recently observed a 66-year-old man whose steady-state serum phenytoin concentration increased 40 percent during one month after the addition to his regimen of ranitidine 150 mg bid. Because the ranitidine had been prescribed postsurgically for prophylaxis, it was discontinued and the patient's serum phenytoin concentration declined to the previous steady-state level with no change in dose or other drug therapy. This case indicates that the serum phenytoin concentration should be monitored for the first month after the addition of ranitidine to the regimens of patients on chronic phenytoin therapy. As well, further clinical investigation of factors affecting the interindividual inhibitory action of ranitidine is warranted.

scholarly journals Transcriptomic and chemical analyses to identify candidate genes involved in color variation of sainfoin flowers

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Qiao ◽  
Qiming Cheng ◽  
Yutong Zhang ◽  
Wei Yan ◽  
Fengyan Yi ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Flower Color ◽  
Color Variation ◽  
Anthocyanin Synthesis ◽  
Flower Formation ◽  
Factors Affecting ◽  
Phenylpropanoid Biosynthesis ◽  
Molecular Information ◽  
Illumina Hiseq4000 ◽  
Insight Into

Abstract Background Sainfoin (Onobrychis viciifolia Scop) is not only a high-quality legume forage, but also a nectar-producing plant. Therefore, the flower color of sainfoin is an important agronomic trait, but the factors affecting its flower phenotype are still unclear. To gain insights into the regulatory networks associated with metabolic pathways of coloration compounds (flavonoids or anthocyanins) and identify the key genes, we conducted a comprehensive analysis of the phenotype, metabolome and transcriptome of WF and AF of sainfoin. Results Delphinidin, petunidin and malvidin derivatives were the main anthocyanin compounds in the AF of sainfoin. These substances were not detected in the WF of sainfoin. The transcriptomes of WF and AF in sainfoin at the S1 and S3 stages were obtained using the Illumina HiSeq4000 platform. Overall, 10,166 (4273 upregulated and 5893 downregulated) and 15,334 (8174 upregulated and 7160 downregulated) DEGs were identified in flowers at S1 and S3 stages, respectively (WF-VS-AF). KEGG pathway annotations showed that 6396 unigenes were annotated to 120 pathways and contained 866 DEGs at S1 stages, and 6396 unigenes were annotated to 131 pathways and included 1546 DEGs at the S3 stage. Nine DEGs belonging to the “flavonoid biosynthesis”and “phenylpropanoid biosynthesis” pathways involved in flower color formation were identified and verified by RT-qPCR analyses. Among these DEGs, 4CL3, FLS, ANS, CHS, DFR and CHI2 exhibited downregulated expression, and F3H exhibited upregulated expression in the WF compared to the AF, resulting in a decrease in anthocyanin synthesis and the formation of WF in sainfoin. Conclusions This study is the first to use transcriptome technology to study the mechanism of white flower formation in sainfoin. Our transcriptome data will be a great enrichment of the genetic information for sainfoin. In addition, the data presented herein will provide valuable molecular information for genetic breeding and provide insight into the future study of flower color polymorphisms in sainfoin.

scholarly journals Factors affecting presence and relative abundance of the Endangered volcano rabbit Romerolagus diazi, a habitat specialist

Oryx ◽  
2021 ◽  
pp. 1-10
Author(s):  
Felipe Osuna ◽  
Roger Guevara ◽  
Enrique Martínez-Meyer ◽  
Raúl Alcalá ◽  
Alejandro Espinosa de los Monteros
Keyword(s):  
Sierra Nevada ◽  
Relative Abundance ◽  
Linear Models ◽  
Cattle Grazing ◽  
Patch Occupancy ◽  
Factors Affecting ◽  
Rock Cover ◽  
Volcanic Fields ◽  
Mountain Grasslands ◽  
Insight Into

Abstract Habitat specialists are particularly vulnerable to extinction when habitat conditions are altered. Information on the habitat use of such species is thus important because it provides insight into factors that influence distribution and abundance, which is crucial for conservation. Here, we aimed to identify factors that influence the patterns of presence and abundance of the Endangered volcano rabbit Romerolagus diazi, a rare leporid with a patchy distribution. Through exhaustive sampling of its range in the Sierra Chichinautzin and Sierra Nevada volcanic fields, Mexico, and using generalized linear models, we found that the probability of patch occupancy was higher where bunchgrass cover exceeded 75%, rock cover exceeded 5%, no cattle grazing was observed and human settlements were at least 7 km away. Patches with greater relative abundance were those with similar characteristics, but located at elevations > 3,600 m, and with rock cover < 15%. Cattle grazing was identified as a major threat to local populations of the volcano rabbit, particularly in the Sierra Chichinautzin. Because of the significance of bunchgrasses for this species, the protection of the mountain grasslands is required in both volcanic fields.

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