Effects of the new nitrosourea derivative, fotemustine, on the glutathione reductase activity in rat tissues in vivo and in isolated rat hepatocytes

The selenium (Se) enrichment of yeasts and lactic acid bacteria (LAB) has recently emerged as a novel concept; the individual health effects of these beneficial microorganisms are combined by supplying the essential micronutrient Se in a more bioavailable and less toxic form. This study investigated the bioavailability of Se in the strains Enterococcus faecium CCDM 922A (EF) and Streptococcus thermophilus CCDM 144 (ST) and their respective Se-enriched forms, SeEF and SeST, in a CD (SD-Sprague Dawley) IGS rat model. Se-enriched LAB administration resulted in higher Se concentrations in the liver and kidneys of rats, where selenocystine was the prevalent Se species. The administration of both Se-enriched strains improved the antioxidant status of the animals. The effect of the diet was more pronounced in the heart tissue, where a lower glutathione reductase content was observed, irrespective of the Se fortification in LAB. Interestingly, rats fed diets with EF and SeEF had higher glutathione reductase activity. Reduced concentrations of serum malondialdehyde were noted following Se supplementation. Diets containing Se-enriched strains showed no macroscopic effects on the liver, kidneys, heart, and brain and had no apparent influence on the basic parameters of the lipid metabolism. Both the strains tested herein showed potential for further applications as promising sources of organically bound Se and Se nanoparticles.

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Comparative metabolism of the antiviral dimer 3'-azido-3'-deoxythymidine-P-2',3'-dideoxyinosine and the monomers zidovudine and didanosine by rat, monkey, and human hepatocytes.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.11.2502 ◽

1997 ◽

Vol 41 (11) ◽

pp. 2502-2510 ◽

Cited By ~ 4

Author(s):

X R Pan-Zhou ◽

E Cretton-Scott ◽

X J Zhou ◽

M Y Xie ◽

R Rahmani ◽

...

Keyword(s):

High Performance ◽

Rat Hepatocytes ◽

Human Hepatocytes ◽

Metabolic Fate ◽

Extracellular Medium ◽

Isolated Rat Hepatocytes ◽

Cell Extracts ◽

Comparative Metabolism ◽

Isolated Rat

AZT-P-ddI is an antiviral heterodimer composed of one molecule of 3'-azido-3'-deoxythymidine (AZT) and one molecule of 2',3'-dideoxyinosine (ddI) linked through their 5' positions by a phosphate bond. The metabolic fate of the dimer was studied with isolated rat, monkey, and human hepatocytes and was compared with that of its component monomers AZT and ddI. Upon incubation of double-labeled [14C]AZT-P-[3H]ddI in freshly isolated rat hepatocytes in suspension at a final concentration of 10 microM, the dimer was taken up intact by cells and then rapidly cleaved to AZT, AZT monophosphate, ddI, and ddI monophosphate. AZT and ddI so formed were then subject to their respective catabolisms. High-performance liquid chromatography analyses of the extracellular medium and cell extracts revealed the presence of unchanged dimer, AZT, 3'-azido-3'-deoxy-5'-beta-D-glucopyranosylthymidine (GAZT), 3'-amino-3'-deoxythymidine (AMT), ddI, and a previously unrecognized derivative of the dideoxyribose moiety of ddI, designated ddI-M. Trace extracellular but substantial intracellular levels of the glucuronide derivative of AMT (3'-amino-3'-deoxy-5'-beta-D-glucopyranosylthymidine [GAMT]) were also detected. Moreover, the extent of the formation of AMT, GAZT, and ddI-M from the dimer was markedly lower than that with AZT and ddI alone by the hepatocytes. With hepatocytes in primary culture obtained from rat, monkey, and human, large interspecies variations in the metabolism of AZT-P-ddI were observed. While GAZT and ddI-M, metabolites of AZT and ddI, respectively, as well as AZT 5'-monophosphate (MP) and ddI-MP were detected in the extracellular media of all species, AMT and GAMT were produced only by rat and monkey hepatocytes. No such metabolites were formed by human hepatocytes. The metabolic fate of the dimer by human hepatocytes was consistent with in vivo data recently obtained from human immunodeficiency virus-infected patients.

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Deuterium isotope effects on toxicity of chloroform and bromobenzene in vivo and to isolated rat hepatocytes

Toxicology Letters ◽

10.1016/0378-4274(83)90305-3 ◽

1983 ◽

Vol 18 ◽

pp. 11

Author(s):

P. Hanzlik Robert ◽

W. Gottschall David

Keyword(s):

Isotope Effects ◽

Rat Hepatocytes ◽

Isolated Rat Hepatocytes ◽

Deuterium Isotope Effects ◽

Isolated Rat

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Correlation of glutathione reductase activity distribution in the blood serum and tissues of white unborn rats

BIO Web of Conferences ◽

10.1051/bioconf/20201700195 ◽

2020 ◽

Vol 17 ◽

pp. 00195

Author(s):

Pavel Boriskin ◽

Olga Gulenko ◽

Anatoly Devyatkin ◽

Rufia Karimova ◽

Victor Leonov ◽

...

Keyword(s):

Blood Serum ◽

Glutathione Reductase ◽

Reductase Activity ◽

Active Oxygen Species ◽

Free Radical Oxidation ◽

Rat Tissues ◽

Activity Distribution ◽

Glutathione Reductase Activity ◽

Nonparametric Correlation ◽

The Relationship

It is known that the majority of pathological processes take place against the background of formation of active oxygen species and intensification of free radical oxidation of bio-substrates. In response to this, the antioxidant system of the cell is activated, and the glutathione system is an important link in this system. The latter can take part in the maintenance of the optimal state of biomembranes, in the processes of detoxification, antioxidant protection, etc. The biological role of glutathione reductase is to maintain high intracellular concentration of reduced glutathione. The aim of our study was to study the relationship between the distribution of glutathione reductase activity in blood serum and rat tissues. In order to achieve the goal of the study the following tasks were solved: the activity of glutathione reductase in blood serum and tissues of liver, brain, heart, as well as in skeletal muscle tissues of rats was determined; the interrelation of the activity distribution of glutathione reductase in blood serum and tissues of rats was revealed. The article presents the results of nonparametric correlation analysis to assess the relationship between the distribution of glutathione reductase activity in blood serum and tissues of small experimental animals.

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Biosynthesis of Methylguanidine in Isolated Rat Hepatocytes and in vivo

Nephron ◽

10.1159/000183523 ◽

1985 ◽

Vol 40 (4) ◽

pp. 470-475 ◽

Cited By ~ 26

Author(s):

Sohji Nagase ◽

Kazumasa Aoyagi ◽

Mitsuharu Narita ◽

Shizuo Tojo

Keyword(s):

Rat Hepatocytes ◽

Isolated Rat Hepatocytes ◽

Isolated Rat

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Influence of mouse age and erythrocyte age on glutathione metabolism

Biochemical Journal ◽

10.1042/bj1740819 ◽

1978 ◽

Vol 174 (3) ◽

pp. 819-825 ◽

Cited By ~ 83

Author(s):

E C Abraham ◽

J F Taylor ◽

C A Lang

Keyword(s):

Glutathione Reductase ◽

Reduced Glutathione ◽

Reductase Activity ◽

Specific Radioactivity ◽

Phthalate Ester ◽

Pulse Labelling ◽

Very Old ◽

Free Thiol ◽

Glutathione Reductase Activity

In order to determine whether the biological age of a mouse influences erythrocyte metabolism and erythrocyte aging in vivo, blood samples were collected from male C57/BL6J mice of different biological ages ranging from mature (10 months) to “very old” (37 months). In the very old mouse, compared with the mature mouse, the erythrocyte survival time was decreased, erythrocyte densities were increased, the concentrations of total free thiol and reduced glutathione, and glutathione reductase activity were decreased. Erythrocytes were separated into different density (age) groups by phthalate ester two-phase centrifugation or by albumin density-gradient centrifugation. The density-age relationship of erythrocytes was established by pulse-labelling with 59Fe in vivo and by subsequent determinations of specific radioactivity of erythrocyte fractions of different densities prepared during a chase period of 60 days. The age of erythrocytes in mice of all ages was directly related to density. Also, in older erythrocytes compared with younger erythrocytes, decreased concentrations of total free thiol and reduced glutathione, and decreased glutathione reductase activity were observed. These were the lowest in the old erythrocytes of very old mice. These results in aging erythrocytes from aging mice suggest that the glutathione status the erythrocyte may be an index of aging, not only of the cell but also of the organism.

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Purine catabolism in isolated rat hepatocytes. Influence of coformycin

Biochemical Journal ◽

10.1042/bj1880913 ◽

1980 ◽

Vol 188 (3) ◽

pp. 913-920 ◽

Cited By ~ 67

Author(s):

Georges Van Den Berghe ◽

Françoise Bontemps ◽

Henri-Géry Hers

Keyword(s):

High Speed ◽

Adenine Nucleotide ◽

Adenine Nucleotides ◽

Rat Hepatocytes ◽

Amp Deaminase ◽

Purine Nucleotides ◽

Isolated Rat Hepatocytes ◽

Adenine Nucleotide Pool ◽

Isolated Rat

1. The catabolism of purine nucleotides was investigated by both chemical and radiochemical methods in isolated rat hepatocytes, previously incubated with [14C]adenine. The production of allantoin reached 32±5nmol/min per g of cells (mean±s.e.m.) and as much as 30% of the radioactivity incorporated in the adenine nucleotides was lost after 1h. This rate of degradation is severalfold in excess over values previously reported to occur in the liver in vivo. An explanation for this enhancement of catabolism may be the decrease in the concentration of GTP. 2. In a high-speed supernatant of rat liver, adenosine deaminase was maximally inhibited by 0.1μm-coformycin. The activity of AMP deaminase, measured in the presence of its stimulator ATP in the same preparation, as well as the activity of the partially purified enzyme, measured after addition of its physiological inhibitors GTP and Pi, required 50μm-coformycin for maximal inhibition. 3. The production of allantoin by isolated hepatocytes was not influenced by the addition of 0.1μm-coformycin, but was decreased by concentrations of coformycin that were inhibitory for AMP deaminase. With 50μm-coformycin the production of allantoin was decreased by 85% and the formation of radioactive allantoin from [14C]adenine nucleotides was completely suppressed. 4. In the presence of 0.1μm-coformycin or in its absence, the addition of fructose (1mg/ml) to the incubation medium caused a rapid degradation of ATP, without equivalent increase in ADP and AMP, followed by transient increases in IMP and in the rate of production of allantoin; adenosine was not detectable. In the presence of 50μm-coformycin, the fructose-induced breakdown of ATP was not modified, but the depletion of the adenine nucleotide pool proceeded much more slowly and the rate of production of allantoin increased only slightly. No rise in IMP concentration could be detected, but AMP increased manyfold and reached values at which a participation of soluble 5′-nucleotidase in the catabolism of adenine nucleotides is most likely. 5. These results are in agreement with the hypothesis that the formation of allantoin is controlled by AMP deaminase. They constitute further evidence that 5′-nucleotidase is inactive on AMP, unless the concentration of this nucleotide rises to unphysiological values.

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