Effects Of Thiamine Tetrahydrofurfuryl Disulfide Research Articles

Vitamin B1 Supplementation Ameliorates Obesogenic Effects of a High Fat Diet in Male Mice

Dietary deficiencies in vitamins such as thiamine (Vitamin B1) are common even in developed countries and can have a range of deleterious health effects. This trend in Vitamin B1 deficiency coincides with increased fat consumption in the American diet, particularly of soybean oil, the most widely consumed cooking oil in the U.S. which is also present in many processed foods. Here, we hypothesized that the concurrent malnutrition caused by a soybean oil-based high fat diet (SO-HFD) and a physiological deficiency in thiamine can exacerbate conditions such as obesity, diabetes, and fatty liver that are associated with consumption of HFDs. To test this, C57BL/6N male mice (N=8-10 per group) were fed either a low-fat chow or an SO-HFD, with or without supplementation with 640 mg/kg of the thiamine analog thiamine tetrahydrofurfuryl disulfide (TTFD), for 18 weeks. Our results showed that the SO-HFD supplemented with TTFD leads to significantly decreased weight gain and delayed the onset of glucose intolerance compared to SO-HFD without added TTFD (p<0.05). In contrast, TTFD supplementation did not have any effect on body weight or glucose intolerance in the context of a low-fat diet. Metabolomic analysis revealed that the SO-HFD decreased absolute thiamine levels both in the blood and liver tissue compared to the low fat control diet (p<0.05); this decrease was reversed by TTFD supplementation suggesting that some of the negative effects of the SO-HFD may be due to its impact on the Vitamin B1 pathway. Untargeted metabolomic analysis identified several other metabolites — such as amino acids, organic acids, methylamine osmolytes and those involved in nucleotide metabolism — that were also affected by TTFD supplementation, but in a beneficial fashion. Transcriptomic analysis of the liver and intestines revealed alterations in thiamine absorption and metabolic pathways by the SO-HFD; effects of TTFD on hepatic gene expression and fatty liver will be presented. TTFD supplementation given after the onset of SO-HFD-induced obesity was not able to reverse the phenotype, suggesting that the deleterious effects of the SO-HFD-induced Vitamin B1 deficiency may be permanent. In conclusion, our findings indicate that consumption of an SO-enriched diet, similar in fat content to what is consumed by most Americans, can result in a Vitamin B1 deficiency. Although TTFD supplementation may mitigate some of the adverse metabolic effects of this diet, this intervention must be done at an early stage. Funding: The Thiamine Advocacy Foundation Research Grant (FMS, PHD, PD); NIH R01DK127082 (FMS)Acknowledgements: UCR Genomics Core Facility, UCR Metabolomics Core Facility, UCR High Performance Computing Center (HPCC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Effects of Thiamine Tetrahydrofurfuryl Disulfide on Physiological Adaption and Exercise Performance Improvement.

Thiamine, named as vitamin B1, is an important cofactor for the critical enzymes regarding to glucose metabolism, like transketolase, pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase. The thiamine tetrahydrofurfuryl disulfide (TTFD) is a derivative of thiamine with higher bioavailability and solubility than thiamine and has been widely applied to health maintenance and disease therapy. Higher physical activities are associated with higher thiamine supplements for efficient energy metabolism. Furthermore, the effective dose of TTFD, beneficial to exercise physiological adaption and performance, still be further validated and the safety evaluation were also an important issue to be considered for potential application. ICR (Institute of Cancer Research) strain mice were allocated as 0, 50, 100, and 500 mg/kg dose groups and administrated by oral gavage consecutively for 6 weeks. Physical activities including grip strength and aerobic endurance were measured. Various fatigue-associated biochemical variables such as lactate, glucose, blood urine nitrogen (BUN) or creatine kinase (CK), were also assessed. The levels of liver and muscle glycogen were measured as an indicator of energy storage at the end of the experiment. Toxicity assessments for long-term supplementation were also further evaluated for safety consideration. TTFD supplementation significantly increased the endurance and grip strength and demonstrated beneficial effects on lactate production and clearance rate after an acute exercise challenge. The TTFD supplementation significantly mitigated the BUN and CK indexes after extended exercise and elevated the glycogen content in the liver and muscle tissues. According to body composition, biochemical and histopathological data, daily administration of TTFD for over 6 weeks (subacute toxicity) also demonstrated reasonable safety results for long-term and adequate supplementation. The toxicity of TTFD were also considered as safety for long-term supplementation with indicated doses. Furthermore, the TTDF could be applied to not only the health promotion but also improvement of exercise physiological adaption and the TTFD could be further considered as potential ergogenic aids combined with different nutrient strategy.

Inhibition of the delayed rectifier K current in guinea-pig cardiomyocytes by thiamine tetrahydrofurfuryl disulfide.

We examined effect of thiamine tetrahydrofurfuryl disulfide on electrophysiological characteristics of single atrial myocytes, obtained by digestion of guinea-pig heart, using collagenase. Membrane potential and ion channel current in the atrial myocytes were recorded by the patch clamp method. Thiamine tetrahydrofurfuryl disulfide prolonged action potentials at cycle lengths from 250 to 10,000 ms. The degree of thiamine tetrahydrofurfuryl disulfide-induced prolongation was similar among these cycle lengths. Thiamine tetrahydrofurfuryl disulfide inhibited the delayed rectifier K+ current, without affecting Ca2+ current and inward-rectifier K+ current. Thiamine tetrahydrofurfuryl disulfide blocked the delayed rectifier K+ current in voltage- and time-independent manner, indicating that thiamine tetrahydrofurfuryl disulfide blocked both subtypes of the delayed rectifier K+ current (rapid and slow components). Thiamine, the parent molecule of thiamine tetrahydrofurfuryl disulfide, blocked the delayed rectifier K+ current only when thiamine was applied intracellularly. Thiamine tetrahydrofurfuryl disulfide may be converted to thiamine in the cytoplasm, and then may block the the delayed rectifier K+ channel from the intracellular side. Although thiamine tetrahydrofurfuryl disulfide (or thiamine) has some of the properties of class III antiarrhythmics agents, thiamine tetrahydrofurfuryl disulfide did not exhibit reverse use-dependent prolongation of action potential.

P-847 - Inhibitory effects of thiamine tetrahydrofurfuryl diSulfide(TTFD) on voltage-gated potassium channels of neurons from rat cerebral cortex.

P-847 - Inhibitory effects of thiamine tetrahydrofurfuryl diSulfide(TTFD) on voltage-gated potassium channels of neurons from rat cerebral cortex.

Inhibition by Thiamine Tetrahydrofurfuryl Disulfide (TTFD) of the Arachidonic Acid Cascade-Line Activation as Evidenced in the Heart-Lung Preparation of the Dog

The effects of thiamine tetrahydrofurfuryl disulfide (TTFD) on the gradual increase in the coronary blood flow (CBF) inherent in the canine heart-lung preparation were studied. TTFD is a disulfide-type derivative of thiamine reported to have an antiinflammatory effect in experimental animals. Since it was found that the substance could reverse the gradual increase in CBF, the possibility that the reversal was brought about through an inhibition of activation of the arachidonic acid cascade-line was tested, examining the effects of this substance on the CBF increase produced by arachidonic acid (AA) and prostacyclin (PGI2). The vasodilator response to AA, which was barely detectable at the start of the experiment at which CBF was at a physiological low level, became potentiated as the gradual increase in CBF occurred, returning to the initial magnitude after TTFD, while the vasodilator response to PGI2 remained essentially unchanged during the entire course of the experiment. It was concluded that TTFD reversed the gradual increase in CBF in the HLP through the inhibition of the arachidonic acid cascade-line activation.

Cardiac action of thiamine derivatives in guinea pig atria.

Pharmacological studies were performed on allithiamine (TAD), thiamine propyl disulfide (TPD), and thiamine tetrahydrofurfuryl disulfide (TTFD) to investigate positive inotropic and negative chronotropic effects seen when they are applied to spontaneous beats in isolated guinea pig atria at concentrations higher than 10-5 g/ml. 1. The effects of thiamine 8-(methyl-6-acetyldihydrothioacetate) disulfide (TATD) and thiamine hydroxyethyl disulfide (TOED) at 5 x 10-4 were slight, and those of dibenzoyl thiamine (DBT) and thiamine were limited at any concentration. 2. Dimethyl propyl disulfide (DMPD) which has anti-thiamine activity, showed these effects at concentrations higher than 10-5. 3. The negative chronotropic effect of TAD, TPD, and TTFD was not influenced by the prior application of atropine, and the positive inotropic effect was not influenced by propranolol. 4. The effects of TTFD on the electrically driven left atrial muscle were remarkable when the muscle was driven at low frequency, while they were less remarkable at high frequency. 5. The decrease in tension of the electrically driven left atria induced by mersalyl at 5 x 10-4 g/ml was recovered by the subsequent addition of TTFD or TPD at 5 x 10-4 as well as dimercaprol at 5 x 10-5. From the results, it was assumed that (a) the effects of TAD, TPD and TTFD might relate to their common chemical structure of the disulfide, especially to the alkyldisulfide chain, (b) the effects are irrevelant to their common activity as an vitamin B1 and to either cholinergic or adrenergic effect, and (c) a mutual dependence is seen between the positive inotropic effect and the negative chronotropic effect.

Effects of low temperature and electrical (square wave) stimulation on spontaneous contractions in isolated guinea pig atria and influence of thiamine tetrahydrofurfuryl disulfide (TTFD) on these effects.

The spontaneous contractions of isolated guinea pig atria were arrested by a temperature change in the medium for 30 to 20 degrees C within 20 min. 2. When thiamine tetrahydrofurfuryl sulfide (TTFD) at concentration of 10-5 g/ml was added in the medium, the arrest was not seen for more than 30 min. 3. Arrhythmic contractions induced by the electrical square wave stimulation of threshold intensity were prevented by TTFD at 10-4 g/ml which was added to the medium. 4. These effects of TTFD at respective concentrations were seen even 30 min after the drug was removed from the medium, when the atria had been pre-incubated with the drug for one hour before the removal. 5. From these results, it was assumed that TTFD might show these effects against the extrinsic physical invasions through the stabilization of the tissue membrane.

Biotransformation of thiamine tetrahydrofurfuryldisulfide and its effect on potassium loss in isolated guinea-pig atria.

In our previous paper, the authors had reported that the reduction in potassium content in isolated guinea-pig atria, kept in a potassium-free medium was prevented by thiamine tetrahydrofurfuryldisulfide (TTFD), added to the medium. In the present experiment, the attempt was to clarify whether or not this drug effect was caused by a biosynthetic thiamine originating from the TTFD. The effect of TTFD was observed in atria which had been treated once with TTFD, then washed out with Locke's solution, and finally subjected to a medium containing a low concentration of potassium ions without TTFD. As this effect seemed to be due to some biosynthetic compound originating from the TTFD, the amounts of thiamine in both the free and the bound forms were chemically estimated. A direct relation, however, could scarcely be found between the effect of TTFD and the amount of biosynthetic thiamine. The effect of TTFD was therefore assumed to be produced by the biotransformation of TTFD in the atria.