Pantothenol protects rats against some deleterious effects of gamma radiation.

Rats were exposed to gamma radiation from a 60Co source, receiving 0.25 Gy at weekly intervals. During 2 d before each irradiation, the animals received daily intragastric doses of 26 mg pantothenol or 15 mg beta-carotene per kg body weight. One hour after the third irradiation session, the animals were killed and their livers were analyzed. In animals not supplied with pantothenol, the irradiation resulted in a significant decrease of total liver lipids and a 50% decrease in phospholipids. Liver cholesterol was decreased by about 20%. Irradiation produced lipid peroxidation as expressed by doubling of the amounts of conjugated dienes and ketone dienes and of thiobarbituric acid reactive compounds. The amount of CoA in liver was decreased by 24% and that of reduced glutathione by 40%. The NAD+/NADH ratio was increased by 60% and the activity of NADP-dependent malate dehydrogenase (decarboxylating) was decreased by 26%. The amount of pantothenic acid and its derivatives (expressed as pantolactone-generating compounds) in blood decreased by about 80%. In rats to which pantothenol was administered, the content of pantothenic acid in blood was tripled compared to nonirradiated (control) rats, and all the biochemical parameters measured in liver were the same as in nonirradiated animals.

Thiamine metabolism in the liver of mice with Ehrlich ascites carcinoma.

Thiamine pyrophosphate (TPP) content, activities of thiamine pyrophosphokinase (TPKase), thiamine pyrophosphatase, transketolase (TK), pyruvate (PDG) and oxoglutarate dehydrogenases (OGDG) were measured in the liver and cells of Ehrlich ascites carcinoma (EAC) on the 5th, 10th and 15th day after transplantation of the tumor to mice fed a thiamine-deficient diet. The TPP level gradually decreased in the liver of tumor-bearing mice but remained constant in tumor cells (1.06 +/- 0.02 microgram/g tissue). Deprivation of dietary thiamine lowered the liver TPP level even to a greater extent, and subsequent daily 10 micrograms thiamine/mouse injections did not restore it. The TPKase activity in the liver of mice with EAC decreased by 24% and in thiamine deficiency, by 44%. The liver PDG, OGDG and TK activities were reduced but slightly in mice with EAC, whereas thiamine deprivation resulted in a decrease of the enzyme activities: PDG by 60%, OGDG by 25% and TK by 45%. TK activity in tumor cells was 90 mumol S-7-P/g tissue/h, and the TPP effect amounted to 24%. Thiamine deprivation decreased the TK activity by 45% and raised the TPP effect up to 180%. Thiamine injections restored the TK activity in tumor cells and reduced the TPP effect.

[Effect of thiamine and its antimetabolite oxythiamine on the proliferative activity of carcinosarcoma Walker 256 cells]. / Vliianie tiamina i ego antimetabolita oksitiamina na proliferatsiiu kletok kartsinosarkomy Uoker 256.

The microscopic studies of tumours from rats injected with thiamine at a dose of 20 mg/kg for 5 days have shown that sites of hemorrhages and necrosis are considerably more extensive than in tumours of control animals. Injections of the same doses of oxythiamine increase the rate of pathologic mitoses in tumour cells and decrease the tumour weight by 45%, limit the synthesis of thiamine diphosphate and inhibit the transketolase activity in tissues.

[Metabolism of vitamin B1 and its di- and triphosphate esters in experimental allergic encephalomyelitis]. / Metabolizm vitamina B1 i ego di- i trifosfornogo efirov pri éksperimental'nom allergicheskom éntsefalomielite.

Biological significance of thiamin in development of experimental allergic encephalomyelitis has been elucidated. It has been shown that at the late preclinical stage of the disease thiamine metabolism is predominantly directed towards the maintaining of cellular metabolic homeostasis, whereas at the stage of clinical symptoms the anabolic process gives way to catabolic decomposition. Among tested thiamine phosphates the triphosphate ester is the most informative parameter in demyelinizing processes. Thiamine injections to immunized animals accelerate the vitamin phosphorylation depleting the reducing and energy potentials of the cell. Such thiamine antagonist as oxythiamine inhibits phosphatase reactions.

[Thiamine diphosphate pool and its biosynthesis in the liver in galactosamine hepatitis]. / Pul tiamindifosfata i ego biosintez v pecheni pri galaktozaminovom gepatite.

The hepatitis-like changes were induced in the liver of albino female rats weighing 120-150 g and fed on the appropriate vivarium diet by single parenteral administration of hydrochloride galactosamine in a dose of 0.9 or 1.8 mmol per 1 kg of body weight. The thiamine diphosphate level in the cytosol fraction of the liver decreased 24 h after the preparation administration, the same in blood but with the higher dose used. The activity of pyruvate dehydrogenase, a thiamine diphosphate dependent enzyme, decreased similarly. The cytosol transketolase activity lowered by 38-39%. The coenzyme biosynthesis disturbance due to a fall by 49-58% in the thiamine pyrophosphatase activity is considered to be responsible for hydrochloride galactosamine-induced decrease in the thiamine diphosphate pool. Specificity of the thiamine diphosphate pool disturbance and discoordination of thiamine diphosphate dependent enzymes in the liver are observed under administration of hydrochloride galactosamine.

[Transketolase activity and the TDP effect in tissues of animals with experimental tumors]. / Aktivnost' transketolazy i TDF-effekt v tkaniakh zhivotnykh s éksperimental'nymi opukholiami.

Activity of transketolase and the TDP-effect were studied in blood and liver subcellular fractions of mice with Erlich ascites carcinoma and of rats with sarcoma 45 which were maintained on a synthetic diet containing either all the vitamins or devoid of thiamine. As compared with other mice liver subcellular fractions the microsomal fraction proved to be the most sensitive to thiamine deficiency: inhibition of transketolase activity reached 75%. Decrease in TDP-effect found in microsomes might reflect the most distinct terminal steps of B1 avitaminosis. As a result of vitamin B1 deprivation of mice with Erlich ascites carcinoma activity of transketolase was decreased by 30% and the TDP-effect increased by 34% in the liver microsomal fraction; in the tumoral cells the enzymatic activity was decreased by 23% and the TDP-effect was increased by 10%. Thiamine-free ration of rats with sarcoma 45, at the initial steps of the tumor growth was responsible for the most distinct decrease in transketolase activity and an increase in the TDP-effect in blood.

[Enzyme activity of thiamine diphosphate biosynthesis and degradation in the mouse liver in the dynamics of B1 avitaminosis development]. / Aktivnost' fermentov biosinteza i degradatsii tiamindifosfata v pecheni myshei v dinamike razvitiia B1-avitaminoza.

Activities of thiamin pyrophosphokinase (TPK EC 2.7.6.2) and thiamin pyrophosphatase (TPPase EC 3.6.1.6) were studied in liver homogenate supernatants obtained from mouse (female, body weight of 21-23 g) in dynamics of B1 avitaminosis. As compared with controls distinct deficiency of thiamin led a decrease in coenzyme thiamin diphosphate (TPP) down to 15% as well as of transketolase activity (TPP-dependent enzyme) down to 35%, especially during the terminal stage of the avitaminosis; the process was accompanied by cyclic alterations in activity of TPK and TPPase. Within 9 and 17 days of the B1 avitaminosis the activity of TPK increased by 62% and 38% and the activity of TPPase--decreased by 30% and 20%, respectively. Alterations in the enzymatic activity appear to be characteristic for adaptation in response to thiamin deficiency.

[Degradation of thiamine diphosphate in subcellular fractions of mouse liver in the dynamics of the development of alimentary B1-avitaminosis]. / Rasshcheplenie tiamindifosfata v subkletochnykh fraktsiiakh pecheni myshei v dinamike razvitiia éksperimental'nogo pishchevogo B1-avitaminoza.

Alterations in activity of specific and unspecific phosphatases, hydrolyzing thiamin diphosphate, were studied in microsomes, mitochondria and cytosol of mice liver cells in dynamics of alimentary B1-avitaminosis (4-21 days). Activity of the enzymes studied was increased as thiamin deficiency developed. Administration of thiamin into the avitaminous animals normalized the enzymatic activity, indicating the specific dependence of these alterations on the thiamin level in animal tissue.

[Thiamine and pyruvate metabolism in tumor-bearing rats]. / Tiamin i obmen piruvata u krys-opukholenositelei.

Correlation between pyruvate and lactate contents as well as between enzymes participating in turnover of the substrates (pyruvate- and lactate dehydrogenases, alanine aminotransferase, pyruvate kinase) were studied in rat liver tissue simultaneously with tumor growth and intensive thiaminotherapy. Thiamine, administered into rats carrying carcinosarcoma Woker-256 at a daily dose 12.5 mg/kg body weight, exhibited the normalizing effect on activity of enzymes studied, on quantitative content of LDH isoenzymes and on content of lactate in blood and of pyruvate in liver tissue. Possible effect of thiamine on pyruvate metabolism in tumoral impairment is discussed.

[Glucose-6-phosphate transformation in the tissues of animals which have received high doses of hydroxythiamine or thiamine]. / Prevrashcheniia gliukozo-6-fosfata v tkaniakh zhivotnykh poluchaiushchikh vysokie dozy oksitiamina ili tiamina.

Administration of hydroxythiamin or thiamin into rats at a dose 400 mg/kg body weight caused a single-directed (unspecific, nonenzymatic) effect on the activity of glucose-6-phosphate and 6-phosphogluconate dehydrogenases within short periods (3-12 hrs). Within 24 and 72 hrs the effects of vitamin and antivitamin acquired the opposite (specific) direction towards the activity of glucose-6-phosphate dehydrogenase in liver tissues. Content of glucose-6-phosphate was altered depending on time of hydroxythiamin effect. Reverse correlation between the activity of glucose-6-phosphate dehydrogenase and content of the substrate was observed in heart muscle either after administration of hydroxythiamin or thiamin; the phenomenon suggest that dehydrogenase reactions affect considerably the regulation of glucose-6-phosphate content in the tissue.

[Features of pyruvate and lactate metabolism in tumor-bearing rats following citrate administration]. / Osobennosti obmena piruvata i laktata u krys-opukholenositelei pri vvedenii im tsitrata.

Everyday administration of citrate (250 mg/kg of body mass) into healthy rats within 4 days inhibited activities of pyruvate kinase, pyruvate dehydrogenase, alanine transaminase and of reverse lactate dehydrogenase in liver tissue but not in sceletal muscles. Within the longer period of citrate administration (8 or 12 days) activities of pyruvate dehydrogenase and alanine transaminase continued to decrease in liver tissue, at the same time, content of pyruvate proceeded to increase in sceletal muscles. More distinct inhibitory effect of citrate on the pyruvate dehydrogenase activity was observed not only in liver tissue but and in sceletal muscles of tumor-bearing animals. Alanine transaminase, which was inactivated in liver tissue of healthy animals after citrate treatment, was markedly activated in tumor-bearing rats in the same conditions. The data obtained suggest that some regulatory functions of citrate were qualitatively transformed in tumor-bearing animals, mainly, in relation to turnover of glucogenic amino acids.

[Effect of oxythiamine on pyruvate and lactate metabolism in rat tissues]. / Vliianie oksitiamina na obmen piruvata i laktata v tkaniiakh krys.

The ratio of two substrates (pyruvate and lactate), activity of enzymes, responsible for their turnover in liver tissue, sceletal muscles and blood, were studied simultaneously in experiments on the effect of hydroxythiamin, which was administered at doses, causing a state of hypovitaminosis B1. Hydroxythiamin was shown to inhibit specifically the activity of thiamin-dependent enzymes (transketolase and pyruvate dehydrogenase). It affected also the metabolism of triose phosphates, pyruvate and lactate. At the same time, hydroxythiamin was responsible for changes in activities of other enzymes, participating in turnover of the substrates studied.

[Lactate level in the tissues of animals with a tumor administered oxythiamine and the properties of lactate dehydrogenase]. / Uroven' laktata v tkaniakh zhivotnykh s opukhol'iu pri vvedenii oksitiaminina i nekotorye svoistva laktatdegidrogenazy.

Content of lactate in blood, liver and kidney tissues, skeletal muscle and in tumor tissue as well as some properties of lactate dehydrogenase (LDH), isolated from liver tissue, were studied in three groups of rats - intact rats, the tumor-bearing animals with sarcoma S-45 and the tumor-bearing rats treated with hydroxythiamin within 22 days. In skeletal muscle on the side of the tumor localization content of lactate was decreased as compared with the opposite side of the body. As shown by analysis of correlation between the content of lactate and the tumor weight and the lactate concentration in the tumor-bearing rat tissues studied, the tumor appears to be responsible for consumption but not for production of lactate. Hydroxythiamin altered distinctly the ratio of lactate content in various tissues and normalized the liver tissue LDH isoenzyme spectrum in tumor-bearing rats; the vitamin decreased 9- and 15-fold the enzyme specific activity in oxidation of lactate in presence of NAD+ and NADP, respectively. After the hydroxythiamin treatment the apparent KM value of the enzyme, isolated from the tumor-bearing rat liver tissue, was increased with pyruvate and decreased with lactate as substrate.

[Transketolase activity and thiamine diphosphate content in oncological patients]. / Aktivnost' transketolazy i uroven' tiamindifosfata u onkologicheskikh bol'nykh.

In blood of patients with cancer of stomach and mammary gland total thiamin content was measured by means of fluorimetric procedure, thiamindiphosphate (TDP)--by an enzymatic method, activity of transketolase was estimated in presence or in absence of TDP. Concentration of total thiamin in blood of healthy persons was 7.65 +/- 0.40 micrograms/100 ml; thiamindiphosphate--5.06 micrograms/100 ml activity of transketolase was 11.59 +/- 0.23 mmol/l. The "TDP" -effect was altered from 4% to 12%. In blood of oncological patients the concentration of total thiamin was 4.47 +/- 0.35 micrograms/100 ml and that of thiamindiphosphate 3.09 +/- 0.27 micrograms/100 ml, i.e. they were decreased by 40%. The transketolase activity was decreased by 20% (9.40 +/- 0.37 mmol/l); the "TDP" -effect was altered from 5% to 42%.

[Biochemical changes in the rat immunocompetent organs during oxythiamine involution of the thymus]. / Biokhimicheskie izmeneniia v immunokompetentnykh organakh krys pri oksitiaminovoi involiutsii timusa.

Oxythiamine injections to rats (400 mg/kg of body mass, subcutaneously, 2 injections with 48 hrs interval) caused 70% involution of thymus within 72 hrs after the first injection. The transketolase activity was inhibited by 70%, that of glucose-6-phosphate dehydrogenase by 15%, while the aldopentose level was decreased by 56% in the thymus. Inhibition of DNA and RNA synthesis was directly dependent on the dose and duration of the oxythiamine effect on the gland. Reduction of transketolase activity was accompanied by an adaptive; increase in glucose-6-phosphate dehydrogenase activity as well as by a decrease in levels of nicotinamide coenzymes (NAD, NADP) in spleen.

[Effects of hydroxythiamine and citrate on several reactions of the pentose phosphate cycle and glycolysis]. / Osobennosti vliianiia oksitiamina i tsitrata na nekotorye reaktsii pentozofosfatnogo tsikla i glikoliza.

Hydroxythiamin was shown to inhibite distinctly phosphofructokinase and phosphohexoisomerase besides a direct antivitaminous effect on transketolase. In this case the regulatory action is likely to be carried out by erythrose-4-phosphate, accumulating in liver tissue. Citrate (administered separately and together with hydroxythiamin) is assumed to influence indirectly the transketolase activity affecting the total regulation of carbohydrate metabolism.

[Metabolism of vitamins B1 and PP and their use in oncological practice]. / Obmen vitaminov B1 i PP i ikh primenenie v onkologicheskoi praktike.

Blood of patients with gastric tumor was studied after their admission to the hospital and after the chemotherapeutic course. Formation of the tumor was accompanied by development of hypovitaminoses B1 and PP. The vitamin deficiency was more distinct after treatment of the patients with cyclophosphan: content of thiamine diphosphate (TDP) was decreased by 40%; NAD+NADP, by 30% and NADH+NADPH, by 20%. In mice with Ehrlich ascites carcinoma, activity of transketolase in erythrocytes was decreased by 48%, content of TDP, by 61% and that of NADPH, by 27%. The administration of cyclophosphan increased further thiamine deficiency in the tumor-bearing mice. Simultaneous administration of thiamine and cyclophosphan abolished the cytostatic toxic effect but did not affect their antitumoral properties. Under these conditions treatment with vitamins B1 and PP complex was undesirable due to malignization. The vitamins B1 and PP did not stimulate the tumor growth, partially restored impaired metabolism of the vitamins and may be included separately into combined multidrug oncotherapeutics.

[The effect of oxythiamine on tumor growth and certain biochemical and genetic characteristics of normal and tumor cells]. / Vliianie oksitiamina na opukholevyi rost i nekotorye biokhimicheskie i geneticheskie kharakteristikie normal'nykh i opukholevykh kletok.

The effect of oxythiamine (400 mg/kg) on chromosomal structure of Ehrlich ascites carcinoma cells (EAC, hyperdiploid strain) and bone marrow cells was studied in intact AF mice. The influence of the antivitamin on the rate of tumor growth was investigated in tumor-bearing mice. Oxythiamine decreased transketolase activity in hepatocytes and tumoral cells and markedly inhibited tumor growth. Amount of chromosomes was unaltered both in tumor cells and in bone marrow cells, which could be manifested as increased content of cells with impairment of chromosomal set calculated per a cell. However, the oxythiamine-induced impairment of chromosomal integrity was less distinct as compared with the effect of such mutagens as urethane and cyclophosphamide; hence, the antivitamin might be used in the courses of combined chemotherapy.

[Interstitial thiamine redistribution during the development of vitamin B1 deficiency in mice]. / Mezhtkanevoe pereraspredelenie tiamina pri razvitii defitsita vitamina B1 u myshei.

Investigation of diphosphothiamine content in the mouse tissues, associated with transketolase activity in the dynamic dependence on the body provision with vitamin B1, has proved the organ-specificity of deposition and elimination of diphosphothiamine under conditions of developing thiamine deficiency. The experimental data have evidenced that vitamin B1 exclusion from the food ration results in the diphosphothiamine redistribution between the tissues and in the provision with coenzymes of one tissue at the expense of the other.

[14C-riboflavin metabolism in mice with Ehrlich's ascitic tumor]. / Obmen 14C-riboflavina u myshei s astsitnoi opukhol'iu Erlikha.

The distribution of 14C-riboflavin in the tissues and elimination of radioactive metabolites with the urine during dynamic development (in 3--5--10 days) of the ascitic Ehrlich's tumour in mice after administration of 10 gamma g per mouse of tagged vitamin in 1--3--24 hr subcutaneously and intragastrically were studied. The development of the neoplastic process was accompanied by a reduced deposition of 14C-riboflavin in the tissues of the macroorganism, an increased elimination of tagged metabolites with the urine, a rising content of the tag in the ascitic fluid. The concentration of the tagged vitamin in the tumour cells remained continuously high in all periods of the test under investigation, its results bearing evidence to an impoverishment of the macroorganism in riboflavial under conditions of the malignant tumour growth.