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Results for “OROTIC ACID”

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At least 19 recordsLinked to original sources
PubMed1976

[The effect of orotic acid and orotic acid derivatives on the in vitro differentiation of hippocampus neurons-morphometric and electron microscopic studies of ribosomes].

1. By means of electron microscopic and quantitative methods at the explantate cultures of the fetal hippocampus in vitro the influence of the orotic acid, sodium orotate and methylglucamine orotate on the neurogenesis was investigated. 2. After three days of the in vitro cultivation the neuroblasts influenced by these drugs show a smaller respectively not different degree of differentiation compared to the controls. 3. Under the influence of the orotic acid and of its derivatives the neurogenesis is significantly stimulated. The drugs produce a significant increase of the membrane-bound ribosomes and polysomes. The total number of ribosomes increases following the application of orotic acid by 20%, of sodium-orotate by 48% and of methylglucamine-orotate by 23% compared to the controls (alpha = 0,1%). 4. Sodium-orotate shows with reference to the neuronal development the clearest stimulatory effect. After 20 days in vitro the total number of ribosomes is by 60% higher at the treated cultures than in the controls. 5. The results might suggest, that an enlarged supply of the pyrimidine nucleotide via a raising of the RNA- and the protein synthesis might stimulate the development of the neuroblasts even under the in vitro conditions.

Animals↗
PubMed1984

[Metabolic effects of orotic acid].

Orotic acid is an important representative of the pyrimidines, the pathophysiological importance of which is less well-known in comparison to the purines. Increases of the excretion of orotic acid in the urine are found e.g. in enzyme defects of the urea cycle, of the orotate phosphoribosyl transferase or the orotidin-5'-monophosphate decarboxylase. Numerous enzymatic systems of the liver are influenced by supply of orotic acid. Toxic influences on the liver may be reduced by orotic acid. In rats orotic acid induces a fatty degeneration of the liver by disturbances of the secretion of lipoproteids. The oxidation of fatty acid by hepatic mitochondria is also reduced by orotic acid. In the blood a decrease of the serum lipid concentrations develops. The effect of the orotic acid in combination with clofibrinic acid was controlled in the double-blind test in patients with hyperlipoproteinaemias. In patients with hyperlipoproteinaemia type V a drastic decrease of the serum lipid concentrations developed and the chylomicrons disappeared from the fasting serum.

Animals↗
PubMed1988

Inhibition of DNA synthesis in primary cultures of hepatocytes by orotic acid.

Orotic acid has been shown to promote carcinogenesis in the liver and the intestine of the rat. In an attempt to determine whether orotic acid promotes liver carcinogenesis by creating differential mitoinhibition, experiments were designed to study the effect of orotic acid on the labeling index of isolated hepatocytes in response to epidermal growth factor. The results indicated that orotic acid added in vitro inhibited epidermal-growth-factor-induced labeling index of isolated hepatocytes. In addition, isolated hepatocytes from rats exposed to orotic acid under promoting conditions also exhibited a decreased response to epidermal growth factor. These data suggest that orotic acid may exert its promoting effect by differentially inhibiting the response of normal hepatocytes to one or more endogenous growth stimuli while permitting the initiated hepatocytes to respond to such stimuli and grow to form hepatic nodules.

Animals↗
PubMed1981

Metabolism of orotic acid: lack of orotate phosphoribosyltransferase in rat intestinal mucosa.

The main enzymes involved in orotic acid metabolism, orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase, are associated as a multienzyme complex (complex U) which is present in the liver of most vertebrate species. Orotic-acid-enriched diets produce increased pyrimidine synthesis which competes with purine synthesis for 5-phosphoribosyl diphosphate, resulting in decreased adenylate levels in liver cells. Inhibition of secretion of very low density lipoproteins and hepatic steatosis is then observed. In contrast, lipoproteins secretion by the intestine is not impaired and fat does not accumulate in enterocytes. The aim of this work was to investigate whether orotate is differently metabolized in gut and in liver thus explaining the lack of effect on the intestinal lipoproteins secretion. Complex U was found in appreciable amounts in rat, mouse and rabbit livers; the intestinal mucosa of the two last species contains a much lower level of multienzyme complex whereas in rat intestine its activity cannot be detected. Indeed, radioactive aspartate and orotate were not incorporated into intestinal cells RNA. The absence of orotate metabolisation by lack of orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase activity in rat intestine would explain why this organ, in contrast to the liver, is protected against disturbances of nucleotide metabolism and lipoproteins secretion induced by orotic-acid-supplemented diets.

Animals↗
PubMed1998

Metabolic supplementation with orotic acid and magnesium orotate.

Orotic acid (OA), a naturally occurring substance, is a key intermediate in the biosynthetic pathway of pyrimidines. Previous investigations in the heart suggest that orotate can protect recently infarcted hearts against a further ischemic stress and may be beneficial in certain types of experimental cardiomyopathy. At the Hamburg symposium on magnesium orotate, a number of studies of this form of metabolic supplementation were presented that indicate orotic acid and its magnesium salt have a modest beneficial effect on the myocardium under conditions of stress ranging from myocardial infarction to severe physical exercise. The following conclusions can be drawn: (1) Orotic acid can improve the energy status of the recently infarcted myocardium (rat hearts). (2) Orotic acid may improve myocardial purine and pyrimidine levels by stimulating hepatic release of uridine into the bloodstream, which in turn augments depleted myocardial pyrimidines and purines (rat heart). (3) Orotic acid improves the tolerance of the recently infarcted heart to global ischemia (rats). (4) Magnesium orotate may reduce the severity of chronic myocardial dysfunction and structural damage in cardiomyopathy (cardiomyopathic hamsters). (5) Magnesium orotate may improve exercise tolerance in patients with coronary artery disease and in trained athletes (humans). (6) Magnesium orotate has only a weak inotropic effect, if any, on normal hearts (rats). (7) Further clinical testing is indicated to determine if the effects described could be of significant clinical benefit in the treatment of heart disease.

Animals↗
PubMed1980

[The effect of orotic acid and sodium orotate on organ cultures of the hippocampus of embryonic rats].

Organ cultures of hippocampus from fetal rats were cultivated in Maximow chambers with semisynthetic media up to 12 days in vitro and fixed after 1, 5 and 12 days in culture, cuted 15 micrometer and coloured with the method of Klüver-Barrera. The effect of 5 x 10(-6) M sodiumorotate and 6 x 10(-6) M orotic acid was tested. 1. The density of cells is related to the zone of cells, the drug and time of incubation. 2. The density of cells increased in the zone of matrix after application of sodiumorotate and orotic acid. The density of cells significantly decreased in the migration zone. The density of neurons significantly increased in the region CA 3. 3. Orotic acid and sodiumorotate influenced the migration of cells in vitro. Sodiumorotate stimulated migration and differentiation. Longtime cultured hippocampi degenerated in vitro after influence of orotic acid. 4. The area of nuclei from neurons increased up to 12 days in vitro, when the cultures were tested with sodiumorotate. Only within the first 24 hours orotic acid effected an increase of the area of nuclei from matrix cells. It is discussed, sodiumorotate influenced in vitro metabolic processes in suitable systems.

Animals↗
PubMed1982

[Electron microscopic and morphometric studies on the in vitro differentiation of mitochondria in neurons of hippocampus explant cultures as affected by orotic acid and sodium orotate].

The influence of orotic acid and sodium orotate on the differentiation of mitochondria of the neurons within explantate cultures of the hippocampus of 18 day old rat embryos was investigated by means of morphometrical and stereological methods. The ultrastructure of the mitochondria in controls and pharmacologically influenced cultures was analysed on electronmicrographs after 3, 13 and 20 days in vitro. According to their morphological appearance and state of preservation the mitochondria were classified in 3 types: juvenile mitochondria (stage I), active mitochondria (stage II) and destroyed mitochondria (stage III). After 3 days of cultivation the neurons in cultures treated with orotic acid and sodium orotate showed significantly higher rates in the numerical density of mitochondria (ratio of the number of all mitochondria per unit volume of cytoplasm) in comparison with controls. Moreover, sodium orotate treatment lead to a significant increase especially in the numerical density of the mitochondria of stage II (active mitochondria) on the third day in vitro. However, the mitochondrial volume per unit volume of cytoplasma of the neurons in drug influenced cultures is lower than in controls for each of these dates--3., 13., and 20. day in vitro. The volume of the mitochondria increased under treatment with sodium orotate from the 3. up to the 20. day of cultivation but never reached the values of the uninfluenced controls. The plastic changes of the mitochondria due to pharmacological treatment with RNA--precursors demonstrate the possibility of a stimulating effect of the drug on the differentiation of neuronal mitochondria in vitro.

Animals↗
PubMed1995

Morphological aspects of the effects of orotic acid and magnesium orotate on hypercholesterolaemia in rabbits.

Heart and blood vessel diseases are one of the leading causes of death, so their prevention and therapy are very important. In the present study the effects of magnesium chloride, magnesium orotate and orotic acid were tested. New Zealand rabbits were fed with enriched (2%) cholesterol diet during 112 days; starting with day 56 all rabbits were treated with MgCl2, Mg-orotate or orotic acid (orally). Aortas, coronaries, renal and femoral arteries were removed and evaluated by morphological and morphometric methods. Atherosclerotic alterations in each vessel could be influenced moderately by Mg-chloride, quite well by orotic acid and excellently by Mg-orotate. From these results one can conclude that orotic acid and Mg-orotate have a beneficial effect in the prevention and therapy of heart and vessels diseases.

Animals↗