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PubMed1981

Changes in the levels and the rate of synthesis of transfer RNA in tissues of mice of different ages.

Levels of transfer RNA (tRNA) were determined in liver, kidney, skeletal muscle, heart, and brain of young (35-day), adult (12-month) and old (24-month) female C57BL/6J mice. Kidney and liver showed little change in tRNA levels between young and adult mice, but the levels decreased in old mice. Skeletal muscle tRNA decreased steadily from young to old mice. Heart tRNA increased during maturation to adult organisms and then decreased in old individuals. Brain levels of tRNA increased steadily. No age-related change in the rate of transport of orotic acid into cells was observed. However, all tissues exhibited a decrease in uridine pools between adult and old mice. Most importantly, all tissues of aging mice showed a decrease in the rate of tRNA synthesis.

Aging↗

PubMed1975

Effects of nutritional factors on the development of ethanol-induced fatty liver in KK and KK-Ay mice.

KK and KK-Ay mice developed a steady and reproducible fatty liver when they were given free access to an ethanol solution as a drinking fluid for 10 to 20 days. The present studies were undertaken to elucidate effects of nutritional factors on liver fat contents of the mice given water or ethanol solution. In contrast to cornstarch, sucrose tended to increase the liver fat of control mice. A higher concentration of dietary casein lowered the liver fat of control mice, whereas the dietary concentration of cottonseed oil did not significantly affect the liver rat levels either in control or ethanol groups. Thus the standard basal diets favorable for the development of the alcoholic fatty liver have been established, for example, 10% cottonseed oil, 25 and 30% casein, 58.4 and 53.4% cornstarch for KK (12-15 weeds old) and KK-Ay (5-10 weeks old), respectively. Neither choline, myoinositol, nor any lipotropic agent tested prevented the development of the alcoholic fatty liver. Unlike in rats, orotic acid did not induce a fatty liver but rather alleviated the ethanol-induced fatty liver in these mice.

Age Factors↗

PubMed1972

Partial ornithine carbamyl transferase deficiency: an inborn error of the urea cycle presenting as orotic aciduria in a male infant.

Recurrent vomiting without apparent cause should alert the physician to the possibility of a disorder of ammonia metabolism. Crystalluria in a three-month-old male infant with a history of intermittent vomiting since birth and incipient coma led to the discovery of orotic aciduria. A diagnosis of ornithine carbamyl transferase (OCT) deficiency was derived from study of the liver after the infant had died; residual activity was about 5% of normal. Ammonia intoxication was the presumed cause of death. Overproduction of orotic acid and other pyrimidines reflects the deficiency of OCT. The possibility of genetic heterogeneity for the hereditary trait under observation must be considered because it may influence prognosis and counselling.

Ammonia↗

PubMed1983

Ultrastructural changes of hepatocyte organelles induced by chemicals and their relation to fat accumulation in the liver.

Fatty liver was induced in the rats shortly after administration of cycloheximide, ethionine, orotic acid, monensin or colchicine. It was strongly suggested that derangements in one or more of the hepatic lipoprotein metabolic steps, which occur at the levels of endoplasmic reticulum, Golgi apparatus and secretory vacuoles lead to an accumulation of triglyceride within hepatocytes.

Animals↗

PubMed1976

Structural and metabolic characterization of RNAs from rats with experimental Guerin tumor - II. metabolic peculiarities of RNAs from the liver and tumor tissues of rats.

Metabolic peculiarities of RNAs in the liver of the tumor bearing and in the tumor tissue were found. The synthesis of nuclear RNA in liver of tumor bearing rats is distinctly disordered in comparison to that of control rats. The level of 14C-orotic acid incorporation into RNA of cancer tissue is manifold lower than that into the liver RNA. The studies on turnover rate showed the metabolic heterogeneity of the nuclear RNAs. The part of them showed a short turnover, the other RNAs were degraded much slower.

Animals↗

PubMed1981

Biosynthesis of cytidine nucleotides in rat liver after administration of D-galactosamine.

Following the administration of D-galactosamine the utilization of [2-14C] orotic acid for the synthesis of the cytidine components of the acid-soluble extract and liver RNA cytosine is markedly decreased. The depression of the specific activity of the cytidine components takes place after application of low doses of the drug which do not interfere with the specific activity of the uridine components of the acid-soluble extract or of liver RNA uracil. Simultaneously the administration of [U-14C]cytidine paralleled by its enhanced liver uptake. The total amount of uridine as well as cytidine components of the acid-soluble extract following the administration of D-galactosamine increases; however, the molar ratio of both pyrimidines does not change. The alterations of the cytidine metabolism after the administration of the drug are accompanied by the increased level of microsomal cytochrome P-450.

Animals↗

PubMed1965

Turnover of ribosomal RNA in rat liver.

After a single injection of radioactive orotic acid and a "chase" of nonradioactive precursor, the specific activity of ribosomal RNA in rat liver decreases logarithmically at a rate corresponding to a half-life of about S days. The possible significance of this result is discussed with regard to control of protein synthesis.

Animals↗

PubMed1975

Influence of phospholipids on liver damage. II. Changes in lipid content and synthesis after liver damage with carbontetrachloride and other agents.

Content and synthesis of lipids were studied in rats after carbontetrachloride poisoning and different treatments with phospholipids (EPL), as well as in some other conditions under which an increase in lipids occurs. The increase in neutral lipids during CCl4 poisoning is significantly reduced by pretreatment and--somewhat less--by posttreatment with EPL. Incorporation of acetate into triglycerides, phospholipids and cholesterol increases in CCl4 poisoning and this was not affected by EPL. Moreover, treatment with EPL had but little effect on the lipid accumulation induced by orotic acid feeding and partial hepatectomy. EPL promoted, however, slightly DNA synthesis after partial hepatectomy and protected DNA in thymus after whole body X-irradiation.

Acetates↗

PubMedDate not supplied

[Peculiarities of RNA synthesis in sections of rat liver tissues and cells of chicken embryos under conditions of protein synthesis inhibition].

Kinetics of radioactive predecessors incorporation into RNA and proteins of the rat liver and chicken embryos cells was studied as affected by different doses of cycloheximide. In both cases a definite dependence is established for changes in the specific radioactivity of nuclei and cytoplasm RNA on the antibiotic concentration: the doses of cycloheximide which cause an insignificant inhibition of protein biosynthesis do not evoke an increase in the intensity of RNA biosynthesis. Intermediate doses of cyclohemide in certain periods of incubation stimulate incorporation of 2-14C-orotic acid into RNA both in experiments with the tissue sections and with cell culture. A dependence is supposed to be between the intracellular bond of the changes in RNA biosynthesis on a degree of protein biosynthesis inhibition.

Animals↗

PubMed1987

Rats fed prolonged high protein diets show an increase in nitrogen metabolism and liver megamitochondria.

Rats were fed diets containing 20, 50 and 80% protein for 14 months. The urea excreted by the rats fed diets containing 50 and 80% protein when compared to rats fed diets containing 20% protein increased ca. 2- and 3-fold, respectively, in ca. 2 days; this increase was maintained essentially unchanged through the experimental period. The serum levels of urea increased 2.5- and 4-fold, respectively, in the first days and were also maintained during the experiment. Glutamate dehydrogenase activity of liver remained unchanged. The five urea cycle enzymes increased with respect to the control values. Orotic acid excretion increased as well as orotidylate decarboxylase and orotate phosphoribosyltransferase, but aspartate transcarbamylase did not. The key amino acids involved in the urea and pyrimidine pathways in liver were also measured; aspartic and glutamic acids and citrulline were increased, and ornithine and arginine did not change with the higher protein intake. In general, no differences were observed between animals fed 50 and 80% protein in their diets. Protein synthesis did not increase with the increase of protein content of the diet. Stereological analysis of ultrathin sections showed that the high protein diet induced a significant increment in the volumetric density, numerical density and size of hepatocyte mitochondria. Moreover, the presence of giant mitochondria, a hundred times larger than normal, was also observed in some periportal hepatocytes of rats fed the 80% protein diet.

Amino Acids↗

PubMedDate not supplied

[Endoprosthesis of the frontonasal anastomosis after extranasal radical operations using biocompatible tubular polymeric materials].

The authors present pilot experience of extranasal radical operations on the frontal sinuses with the use of polymeric tube endoprostheses made of biocompatible polymeric materials EFOS 1, 2, 3 containing antimicrobial drugs (dioxidin, chinoxidin) and active substances promoting regeneration and epithelization (orotic acid derivatives). The above technique was employed in operations on frontal sinuses in 12 patients. Polymeric endoprostheses EFOS provide adequate lumen of the formed frontonasal anastomosis, reduce the occurrence of postoperative complications and recurrences as well as hospital stay.

Anastomosis, Surgical↗

PubMed1977

Dependence of the composition of the protein moiety of nuclear ribonucleoprotein particles on the extent of particle purification as studied by electrophoresis including a two-dimensional procedure.

Extraction with 0.1 M NaCl in 0.01 M Tris-HCl buffer, pH 8.0 releases from liver nuclei 30-40-S ribonucleoprotein particles containing newly synthesized RNA. Separation of the protein moiety of these particles by acid-urea gel electrophoresis depends on the concentration of beta-mercaptoethanol in the buffer used for the solubilization of the particles. At low concentration or with short time of solubilization, only a polypeptide chain with apparent molecular weight 38 000 penetrates into the gel and can be detected by electrophoresis. By introduction of two-dimensional polyacrylamine gel electrophoresis, we succeeded to separate the protein moiety of these particles into a core group of 4 major and 6 minor polypeptides with molecular weights ranging from 38 000 to 50 000 and a second group of 19 polypeptides ranging in molecular weight from 50 000 to 120 000. The composition of the protein moiety of these particles is dependent on the extent of purification. Polypeptides with molecular weight below 50 000 represent 55% of the total protein of particles purified only by centrifugation through a 15-30% sucrose gradient. If the particles were first purified by gel filtration through Bio-Gel A-50m followed by centrifugation in sucrose gradient, the low molecular weight proteins represent 80% of all the proteins of the particles. The purification removed selectively the minor high molecular weight polypeptides without resulting in any extensive release of the four major polypeptides with molecular weight below 50 000 which form a stable core particle. By repeated purification it is possible to strip the particles of the high molecular weight polypeptides even further. An increase in the NaCl concentration of the extraction buffer to 0.35 M will extract additional 30-40-S particles associated with a newly synthesized RNA from the cell nucleus. These particles contain the same polypeptides as particles extracted at lower salt concentration. Extraction with 0.1 M and 0.35 M NaCl at pH 8.0 removed from the nucleus approximately 55% of all RNA labeled in 30 min after intraperitoneal injection of [3H] orotic acid to the rats.

Animals↗

PubMed1981

Enzyme induction in rat liver: the effects of Be2+ in vivo.

Rats given an LD50 dose of Be2+ showed reduced activities of ornithine decarboxylase and tyrosine aminotransferase in liver in response to dexamethasone induction. Control fed animals showed 'superinduction'. Be2+ also inhibited the uptake of [3H]orotic acid into rapidly labelled RNA of ribonucleoprotein particles extracted from liver nuclei in isomolar solutions at pH 8.0. Consistent with inhibition of cytoplasmic protein kinase reported previously (Kaser et al., 1980), the uptake of [32P]Pi into proteins in the ribonucleoprotein particles was also diminished.

Animals↗

PubMed1976

Metabolism and metabolic effects of 8-azainosine and 8-azaadenosine.

8-Azainosine (8-aza-HR) is of interest because of its activity against experimental tumors. Metabolic studies in cell cultures were performed with 8-aza-HR and with the structurally related nucleoside, 8-azaadenosine (9-beta-D-ribofuranosyl-8-azaadenine) (8-aza-AR), which has a lower degree of antitumor activity than does 8-aza-HR. In H. Ep. 2 cells and in Ca755 cells, both 14C-labeled nucleosides were metabolized to nucleotides of 8-azaadenine (8-aza-A) and 8-azaguanine (8-aza-G) and incorporated into polynucleotides as 8-aza-A and 8-aza-G. 8-Aza HR was incorporated primarily as 8-aza-G, whereas 8-aza-AR was incorporated about equally as 8-aza-A and 8-aza-G. In H. Ep. 2 cells, the extent of incorporation of 8-aza-HR as 8-aza-G was about one-half that found when [14C]-8-aza-G was the precursor. In the H. Ep. 2/FA/FAR cell line, 8-aza-AR and 8-aza-HR were metabolized similarly, in that both were incorporated into polynucleotides principally as 8-aza-G; apparently, in this cell line which is deficient in adenosine kinase and adenine phosphoribosyltransferase, 8-aza-AR is metabolized by conversion to 8-aza-HR. A cell line (H. Ep 2/8-aza HR), which was resistant to 8-aza-HR but sensitive to 8-aza-AR and which retained hypoxanthine (guanine)-phosphoribosyltransferase activity, metabolized 8-aza-HR to only a small extent. However, in this cell-line, 8-aza-AR was more extensively metabolized and was incorporated primarily as 8-aza-A. The failure of these cells to convert 8-aza-AR or 8-aza-HR to 8-aza-G indicates that the basis for resistance may be a change in the substrate specificities of the enzymes of guanosine monophosphate synthesis such that these cells no longer effectively convert 8-azainosine monophosphate to 8-azaguanosine monophosphate. 8-Aza-AR was a potent inhibitor of purine synthesis de novo, but 8-aza-HR, at concentrations much higher than the inhibitory concentration of 8-aza-AR, did not inhibit this process. In H. Ep. 2 cells, 8-aza-HR blocked the conversion of orotic acid to uridine nucleotides and caused an accumulation of orotidine. This inhibition of pyrimidine biosynthesis apparently does not contribute significantly to the cytotoxicity of 8-aza-HR because uridine provided no degree of reversal of its inhibition of the growth of cell cultures.

Adenosine↗

PubMed1976

Effect of tryptophan on polyriboadenylic acid and polyadenylic acid-messenger ribonucleic acid in rat liver.

The administration of tryptophan to fasted rats 1 hour before killing resulted in marked increases in the amounts of hepatic polyriboadenylic acid (poly(A)) and poly(a)-containing-mRNA in the cytoplasm and a shift in hepatic polyribosomes toward heavier aggregates. When animals were treated with cordycepin, or actinomycin D, to both, there was disaggregation of hepatic polyribosomes and inhibition of poly(A) synthesis. Administration of tryptophan to fasted animals pretreated with cordycepin, or actinomycin D, or both induced a shift in hepatic polyribosomes toward heavier aggregates and an increase in in vitro protein synthesis. Fasted rats that received [U-14C] adenosine to prelabel hepatic poly (A) and then were treated with cordycepin, or actinomycin D, or both before tubefeeding tryptophan revealed increased hepatic levels of labeled polyribosomal poly (A) in comparison with controls. Fasted rats that received 14C-orotic acid to prelabel poly (A)-mRNA and then were treated with actinomycin D after 1 hour and with tryptophan along with cycloheximide after 1 1/2 hours revealed marked increases in labeling of hepatic poly (A)-mRNA associated with polyribosomes in comparison with controls. These findings suggest that tryptophan may act to stimulate the transport of poly (A)-containing-mRNA into the cytoplasm of the liver.

Adenosine↗

PubMedDate not supplied

[Metabolism of uridine triphosphate in rat liver].

Thiamin - a predecessor of transketolase coenzyme is shown to cause an increase in the intensity of labelled 14C orotic acid incorporation into UDP and UTP of the rat liver though the time of UTP exchange remains unchanged. Taking into account the data obtained, an assumption is advanced that the biosynthesis of pentoses in the pentosophosphate way of carbohydrates transformation in the rat liver proceeds in its non-oxidative branch with transketolase and transaldolase participating in the process.

Animals↗

PubMedDate not supplied

[Anxiolytic effect of potassium orotate].

Chronic administration of potassium orotate to rats per os in a dose of 100 mg/kg produces anxiolytic action that is manifested in antiaggressive, antiphobic and anti-conflict effects similar to the characteristic effects of diazepam. Besides, it provokes the changes in the spectral characteristics of the cat brain electrograms, common to tranquilizers. Based on the data obtained and analysis of the reported evidence the authors advance the hypothesis according to which endogenous pyrimidines, particularly orotic acid, possessing structural fragments necessary for the interaction with the sites of specific binding of 1,4-benzodiazepines may realize adaptive anxiolytic function both within the system of metabolic adaptation and when involved into the system of endogenous regulators and modulators of neuropsychic processes.

Aggression↗

PubMed1980

Inhibition by ethionine and beta-diethylaminoethyl diphenylpropylacetate of RNA and protein synthesis in the rat liver, and its reversal by pregnenolone-16 alpha-carbonitrile.

The effect of pregnenolone-16 alpha-carbonitrile (PCN) on female Sprague-Dawley rats was studied in conjunction with ethionine and beta-diethylaminoethyl diphenylpropylacetate (DADP). The cyanosteroid virtually abolished in inhibitory action of ethionine on orotic acid and leucine uptake by liver microsomes. When PCN was given conjointly with DADP, it completely overshadowed the latter's effect on leucine uptake. DADP was found to act as an inhibitor of the translational mechanism 5 h after its administration, while it exerted a stimulatory influence on the transcriptional mechanism after the same time period.

Animals↗