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PubMed1982

Effects of treatment with thiamin antagonists, oxythiamin and pyrithiamin and of thiamin excess of the levels and distribution of thiamin in rat tissues.

Levels of thiamin and its derivatives in brain, heart and liver were determined in control, thiamin-deficient, pyrithiamin-treated and oxythiamin-treated rats at various times after the start of treatment. With 10 micrograms of thiamin/100 g/day subcutaneously, rats rapidly lost thiamin from the tissues until growth maintenance levels were reached. Oxythiamin had a minimal further effect on tissue thiamin while pyrithiamin caused further marked reduction. With higher levels of thiamin intake, tissue thiamin levels increased with intakes of up to 150-200 micrograms/100 g/day after which they did not show any further significant increase. Levels of pyrithiamin above 50 microgram/100 g/day for 20 days had only minimal further effect upon tissue thiamin levels over that with 50 micrograms.

Animals↗
PubMedDate not supplied

[Effects of nicotinamide and oxythiamine on the lipogenic parameters of the adipose tissue of mice with non-insulin-dependent type of experimental diabetes mellitus and hyperinsulinemia].

The influence of nicotinamide and oxythiamine on the activity of NADPH-producing dehydrogenases of glucoso-6-phosphate, 6-phosphogluconate, malate, isocitrate, as well as concentration and synthesis rate of fatty acids in fatty tissue were studied in experiments on mice with genetically conditioned non-insulin-dependent diabetes and hyperinsulinemia. It has been established that in these diseases the synthesis of fatty acids and their inclusion into lipids are activated without increasing the above enzymes activity. It is shown that nicotinamide and oxythiamine inhibit inclusion of C from glucose into free fatty acids, antivitamin intensifies lipolysis in the fatty tissue of the diseased animals.

Adipose Tissue↗
PubMedDate not supplied

[Comparative antivitamin activity of oxythiamine disulfide and its monosulfoxide].

The B1-antivitamin activity of oxythiamine disulphide monosulphoxide has been determined in experiments on albino mice. It is shown that this derivative is less toxic and exerts a more profound and prolonged inhibitory action on the pyruvate dehydrogenase and transketolase activity in the animal body in comparison with initial oxythiamine disulphide.

Animals↗
PubMedDate not supplied

[Specific activity of thiamine and oxythiamine immobilized on modified cellulose].

The effect of thiamine and oxythiamine preparations on the activities of vitamin B1-dependent enzymes in the body of white mice was studied. It was found that the cellulose oxythiamine derivative was similar to the initial compound in the character and intensity of its antivitamin action. It was also shown that the cellulose thiamine derivative had a prolonged effect in the body, which was manifested in a slower increase in the activities of transketolase, pyruvate dehydrogenase and in the amount of thiamine diphosphate in tissues of vitamin B1-deficient animals, as compared to the effect of thiamine.

Animals↗
PubMedDate not supplied

[Biochemical changes in the rat immunocompetent organs during oxythiamine involution of the thymus].

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.

Animals↗
PubMed1984

[Lactate and pyruvate metabolism in the tissues of rats with Walker carcinosarcoma injected with oxythiamine].

The levels of L-lactate and pyruvate as well as the enzymes of their conversion (lactate dehydrogenase in direct and reverse reactions, pyruvate dehydrogenase, pyruvate kinase, alanine transaminase) have been studied simultaneously in the liver and skeletal muscle of rats bearing carcinosarcoma Walker 256, control animals and after additional oxythiamine administration. Properties of oxythiamine independent of its anticoenzymic activity manifest themselves in the body of tumour-bearing animals to a greater extent. After the antivitamin administration there occur strong inhibition of pyruvate kinase, activation of alanine transaminase, normalization of the L-lactate level in the tissues.

Alanine Transaminase↗
PubMedDate not supplied

[Carbohydrate metabolic index change in the liver on the administration of thiamine or oxythiamine to rats with a varying hormonal level].

The effects of thiamine and oxythiamine on glucoso-6-phosphate, fructoso-6-phosphate, ATP, aldopentoses, glucose and glycogen levels were studied in the liver of rats with different hormonal levels. Thiamine and insulin were shown to produce a similar effect on the liver levels of hexosomonophosphates, aldopentoses and glucose. Oxythiamine effects as compared to those elicited by thiamine and insulin are always contrasting. It is suggested that the insulin-like action of thiamine is consequent on the primary effect the vitamin exerts on the functional activity of the insular apparatus of the pancreas.

Adrenalectomy↗
PubMed1990

Dominant resistance to oxythiamin in Saccharomyces cerevisiae and its mapping.

A dominant mutation, responsible for the resistance to oxythiamin in Saccharomyces cerevisiae was mapped on the right arm of chromosome IV, 4.6 cM centromere-distally to trp1. The corresponding gene is not involved in the control of intracellular content of total thiamin during growth on a minimal medium without thiamin.

Chromosome Mapping↗
PubMed1999

Oxythiamine and dehydroepiandrosterone induce a G1 phase cycle arrest in Ehrlich's tumor cells through inhibition of the pentose cycle.

Transketolase (TK) reactions play a crucial role in tumor cell nucleic acid ribose synthesis utilizing glucose carbons, yet, current cancer treatments do not target this central pathway. Experimentally, a dramatic decrease in tumor cell proliferation after the administration of the TK inhibitor oxythiamine (OT) was observed in several in vitro and in vivo tumor models. Here, we demonstrate that pentose cycle (PC) inhibitors, OT and dehydroepiandrosterone (DHEA), efficiently regulate the cell cycle and tumor proliferation processes. Increasing doses of OT or DHEA were administered by daily intraperitoneal injections to Ehrlich's ascites tumor hosting mice for 4 days. The tumor cell number and their cycle phase distribution profile were determined by DNA flow histograms. Tumors showed a dose dependent increase in their G0-G1 cell populations after both OT and DHEA treatment and a simultaneous decrease in cells advancing to the S and G2-M cell cycle phases. This effect of PC inhibitors was significant, OT was more effective than DHEA, both drugs acted synergistically in combination and no signs of direct cell or host toxicity were observed. Direct inhibition of PC reactions causes a G1 cell cycle arrest similar to that of 2-deoxyglucose treatment. However, no interference with cell energy production and cell toxicity is observed. PC inhibitors, specifically ones targeting TK, introduce a new target site for the development of future cancer therapies to inhibit glucose utilizing pathways selectively for nucleic acid production.

Animals↗
PubMed1981

[Effects of repeated administration of pyrithiamine and oxythiamine on timing behavior in rats (author's transl)].

Male Wistar rats were trained to hold down a lever for reinforcement with food pellets. No external stimulus signalled the end of the required duration. The minimum duration required was gradually raised to, and fixed at, 2 seconds. This was achieved in about 1-2 months. At the end of pre-drug training, the average response duration was 2.06 +/- 0.03 seconds in a daily 10-minute session. Daily injections of pyrithiamine, a thiamine analog which causes a rapid depletion of the brain vitamin, were given after the daily experimental session. The average response duration increased significantly by the 8th day of pyrithiamine treatment (2 mg/kg/day), without altering any other parameters examined. This pyrithiamine-induced change in duration, which was gradually diminished after the 14-day drug period, could be reversed with thiamine (2 doses of 5 mg/kg). On the other hand, oxythiamine did not cause an increase in duration over the 14 days of daily injections. The results obtained suggest that pyrithiamine exerted significant effects on discrimination of duration or internal timing mechanism in rats at the doses used, perhaps because of the depletion of the brain vitamin.

Animals↗
PubMed1981

[Effect of oxythiamine and pyrithiamine on thiamine levels in the blood, liver and urine of rats (author's transl)].

Thiamine (T) deficient state and various functional and morphological changes in rat liver were induced, after several days, with T antagonists, oxythiamine (OT) or pyrithiamine (PT), and a thiamine deficient diet (TDD). The relationship between the extent of liver damage and T levels in blood, liver and urine were studied in OT treated rats fed a TDD (OTD group). PT treated rats fed a TDD (PTD group), OT treated rats (OT group), PT treated rats (PT group) and rats fed a TDD (TDD group). The T levels in blood and liver of OT group, PT group, OTD group, PTD group and TDD group were 89% and 91%, 76% and 88%, 25% and 14%, 33% and 16%, 24% and 15% compared with the data in the control group, respectively. Effects of OT or PT on T levels were not remarkable in some cases, and such may be due to the duration time of T antagonists, which was considered to be 3-15 hours in PT treated rats, and 0-18 hours in PT treated rats, as assessed by urinary T measurements. Treatment of T antagonist twice daily is recommended to obtain a definite T deficient state. Our results suggest that the extent of liver damage is related to the T levels in tissue.

Animals↗
PubMedDate not supplied

[Hypolipidemic effect of the antivitamin B1 oxythiamine in diabetic mice (db/db)].

A rate of lipogenesis from 1-14C-acetate and 2-14C-pyruvate as well as total cholesterol, diene conjugates, malonic dialdehyde were increased in liver tissue of mice db/db strain with genetically determined diabetes, whereas content of free fatty acids was not distinctly altered despite of the marked elevation of corticosterone in blood plasma. Ratio of atherogenic lipoproteins VLDL and LDL was increased in blood plasma of these mice with diabetes. As oxythiamine, administered into the mice, exhibited hypolipidemic and antioxidant effects, TDP-dependent reactions appear to be among the factors responsible for deterioration of lipid metabolism in the diabetes.

Animals↗
PubMed1987

[Effect of thiamine and its antimetabolite oxythiamine on the proliferative activity of carcinosarcoma Walker 256 cells].

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.

Animals↗
PubMedDate not supplied

[Thiamine pyrophosphate-dependent enzymes in the regenerating liver of albino rats under different regimens of oxythiamine administration].

Activities of the thiamine pyrophosphate-dependent enzymes (pyruvate dehydrogenase, oxoglutarate dehydrogenase, transketolase) were increased in regenerating rat liver tissue as compared with their activities in the intact tissue. After administration of oxythiamine (20 mg/kg, within 10 days, subcutaneously) into the animals the enzymatic activity studied was decreased.

Animals↗
PubMed1979

[Effects of oxythiamine and pyrithiamine on rat liver. --Biochemical and morphological changes in the thiamine deficient rat (author's transl)].

We studied biochemical changes in the rat liver in a thiamine (T) deficient state as induced by oxythiamine (OT), pyrithiamine (PT) and thiamine deficient diet (TDD) and simultaneously observed morphological changes under light and electron microscope. Severe loss of weight was observed in the OT treated rats fed on TDD (OTD) and such was frequently accompanied by a complete loss of righting reflex. Biochemical changes commonly found in T deficient groups were decrease in serum total protein, alkaline phosphatase activity and liver lipids, and increase in serum total cholesterol and transaminase activity. Microscopically, most of the liver cells were atrophied and necrosis was observed in the OTD group. Electron microscopically, ultrastructural changes revealed active Kupffer cells, microvilli and Golgi apparatus, and decrease in rough endoplasmic reticulum (rER) associated with increasing detached ribosomes and smooth ER. Abnormal nucleus and mitochondria were found in the OTD group. These results suggest that a T deficiency occurs readily and easily within a short time when a T antagonist, particularly OT, is used together with the TDD, while a much longer time is required to produce a T deficiency with only the TDD.

Animals↗
PubMed1981

[Morphogenesis of thymus involution during oxythiamine B1-hypovitaminosis].

Atrophy of the thymus cortex was found in rats after administration of oxythiamine. In acute experiments, atrophy was a consequence of a short-term inhibition of proliferation followed by enhancement of disintegration of small thymocytes by caryorhexis. Disintegration assumes an exceptional significance for thymus involution. Breakdown of cells correlated with a sharp decrease in thymocyte resistance to hydrocortisone. Possible metabolic reasons for the decreased resistance are discussed.

Animals↗
PubMed1982

[Effect of oxythiamine on rat peripheral nerve. --Morphological changes in sciatic nerve and plantar nerve of thiamine deficiency-- (author's transl)].

Morphological changes in rat sciatic nerve (SN) and plantar nerve (PN) induced by a thiamine deficient diet (TDD) and administration of oxythiamine (OT: 4 mg/100 g X 6 days) were observed, and thiamine (T) levels in rat nerve were simultaneously determined. Body weight gain ratio in rats which received OT fed a TDD (OTD group) was much reduced, and anorexia and ataxia were recognized in this group. Rats fed a regular diet, whose weights were restricted to be the same as those in the OTD group (EWC group), showed the symptoms of starvation. T levels of the SN and PN in the OT group, OTD group, and rats fed a TDD (TDD group) were reduced, but in the EWC group, T levels were the same as those in the control group (C group). There were myelin folds and myelin oboids in the EWC group, and these were recognized before axonal degeneration. In the TDD group, an increase in the number of mitochondria (Mit) was seen in the myelinated axon (MAx). In the TDD group, an increase in the number of mitochondria (Mit) was seen in the myelinated axon (MAx). In the OT and OTD groups, axonal degeneration (increase in the number of Mit, appearance of degenerated Mit, axonal shrinkage, and disappearance of neurofilament and neurotubule) was observed in the MAx. Degeneration of the MAx caused by TDD and OT was more severe in the PN than in the SN. Since these changes progressed from the peripheral nerve to the centripetal one, these changes in OTD group might be dying-back polyneuropathy.

Animals↗
PubMed1982

[Corticosteroid mechanism as a leading element of the thymotropic effect of oxythiamine in the rat].

Oxythiamine B1-hypovitaminosis in adrenalectomized male rats is not accompanied by acute thymus involution. This is not so much related to hypocorticoidism per se, as to a decrease in metabolic potencies of the antivitamin, particularly to a negligible depression of thymocyte tolerance to hydrocortisone. Sex differences in morphological parameters of thymus lymphopoiesis have been found after adrenalectomy.

Adrenalectomy↗