Taurine Abstracts 11

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Therapeutic applications of taurine.
            (Birdsall, 1998)  Download
Taurine is a conditionally-essential amino acid which is not utilized in protein synthesis, but rather is found free or in simple peptides. Taurine has been shown to be essential in certain aspects of mammalian development, and in vitro studies in various species have demonstrated that low levels of taurine are associated with various pathological lesions, including cardiomyopathy, retinal degeneration, and growth retardation, especially if deficiency occurs during development. Metabolic actions of taurine include: bile acid conjugation, detoxification, membrane stabilization, osmoregulation, and modulation of cellular calcium levels. Clinically, taurine has been used with varying degrees of success in the treatment of a wide variety of conditions, including: cardiovascular diseases, hypercholesterolemia, epilepsy and other seizure disorders, macular degeneration, Alzheimer's disease, hepatic disorders, alcoholism, and cystic fibrosis.

Fluid and electrolyte replacement in renal failure
            (EDREN, 2020)  Download

Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation.
            (Franconi et al., 1995)  Download
Plasma and platelet taurine concentrations were assayed in 39 patients with insulin-dependent diabetes mellitus (IDDM) and in 34 control subjects matched for age, sex, and both total and protein-derived daily energy intake. Platelet aggregation induced by arachidonic acid in vitro at baseline and after oral taurine supplementation (1.5 g/d) for 90 d was also studied. Plasma and platelet taurine concentrations (mean +/- SEM) were lower in diabetic patients (65.6 +/- 3.1 mumol/L, or 0.66 +/- 0.07 mol/g protein) than in control subjects (93.3 +/- 6.3 mumol/L, or 0.99 +/- 0.16 mol/g protein, P < 0.01). After oral supplementation, both plasma and platelet taurine concentrations increased significantly in the diabetic patients, reaching the mean values of healthy control subjects. The effective dose (mean +/- SEM) of arachidonic acid required for platelets to aggregate was significantly lower in diabetic patients than in control subjects (0.44 +/- 0.07 mmol compared with 0.77 +/- 0.02 mmol, P < 0.001, whereas after taurine supplementation it equaled the mean value for healthy control subjects (0.72 +/- 0.04 mmol). In in vitro experiments, taurine reduced platelet aggregation in diabetic patients in a dose-dependent manner, whereas 10 mmol taurine/L did not modify aggregation in healthy subjects.

Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus.
            (Jia et al., 2008) Download
Taurine is one of the most abundant free amino acids in the brain. In a number of studies, taurine has been reported to activate glycine receptors (Gly-Rs) at moderate concentrations (> or = 100 microM), and to be a weak agonist at GABA(A) receptors (GABA(A)-Rs), which are usually activated at high concentrations (> or = 1 mM). In this study, we show that taurine reduced the excitability of thalamocortical relay neurons and activated both extrasynaptic GABA(A)-Rs and Gly-Rs in neurons in the mouse ventrobasal (VB) thalamus. Low concentrations of taurine (10-100 microM) decreased neuronal input resistance and firing frequency, and elicited a steady outward current under voltage clamp, but had no effects on fast inhibitory synaptic currents. Currents elicited by 50 microM taurine were abolished by gabazine, insensitive to midazolam, and partially blocked by 20 microM Zn2+, consistent with the pharmacological properties of extrasynaptic GABA(A)-Rs (alpha4beta2delta subtype) involved in tonic inhibition in the thalamus. Tonic inhibition was enhanced by an inhibitor of taurine transport, suggesting that taurine can act as an endogenous activator of these receptors. Taurine-evoked currents were absent in relay neurons from GABA(A)-R alpha4 subunit knock-out mice. The amplitude of the taurine current was larger in neurons from adult mice than juvenile mice. Taurine was a more potent agonist at recombinant alpha4beta2delta GABA(A)-Rs than at alpha1beta2gamma2 GABA(A)-Rs. We conclude that physiological concentrations of taurine can inhibit VB neurons via activation of extrasynaptic GABA(A)-Rs and that taurine may function as an endogenous regulator of excitability and network activity in the thalamus.

Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats.
            (Katakawa et al., 2016) Download
Endothelial damage is repaired by endothelial progenitor cells (EPCs), which are pivotal in preventing cardiovascular diseases and prolonging lifespan. The WHO Cardiovascular Diseases and Alimentary Comparison Study demonstrated that dietary taurine and magnesium (Mg) intake suppresses cardiovascular diseases. We herein evaluate the effects of taurine and Mg supplementation on EPC function and oxidative stress in healthy men and spontaneously hypertensive rats (SHRs). Healthy men received taurine (3 g per day) or Mg (340 mg per day) for 2 weeks. SHRs and Wistar-Kyoto (WKY) rats were housed with high-salt drinking water (1% NaCl). The SHRs received 3% taurine solution and/or a high-Mg (600 mg per 100 g) diet for 4 weeks. Their peripheral blood mononuclear cells were separated to quantify EPC colony formation. Oxidative stress markers in their peripheral blood were evaluated using a free radical analytical system and a thiobarbituric acid reactive substance (TBARS) assay. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased free radical levels and TBARS scores in healthy men. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased TBARS scores and free radical levels in SHRs. Nicotinamide adenine dinucleotide phosphate oxidase component mRNA expression was significantly higher in the renal cortex of salt-loaded SHRs than in WKY rats, in which it was suppressed by taurine and Mg supplementation. Taurine and Mg supplementation increased EPC colony formation in healthy men and improved impaired EPC function in SHRs through antioxidation, indicating that the dietary intake of taurine and Mg may prolong lifespan by preventing the progression of cardiovascular diseases.

Taurine-magnesium coordination compound, a potential anti-arrhythmic complex, improves aconitine-induced arrhythmias through regulation of multiple ion channels.
            (Lou et al., 2018) Download
Taurine-magnesium coordination compound (TMCC) exhibits antiarrhythmic effects in cesium-chloride-and ouabain-induced arrhythmias; however, the mechanism underlying these effects on arrhythmia remains poorly understood. Here, we investigated the effects of TMCC on aconitine-induced arrhythmia in vivo and the electrophysiological effects of this compound in rat ventricular myocytes in vitro. Aconitine was used to induce arrhythmias in rats, and the dosages required to produce ventricular premature contraction (VPC), ventricular tachycardia (VT), ventricular fibrillation (VF), and cardiac arrest (CA) were recorded. Additionally, the sodium current (INa) and L-type calcium current (ICa,L) were analyzed in normal and aconitine-treated ventricular myocytes using whole-cell patch-clamp recording. In vivo, intravenous administration of TMCC produced marked antiarrhythmic effects, as indicated by the increased dose of aconitine required to induce VPC, VT, VF, and CA. Moreover, this effect was abolished by administration of sodium channel opener veratridine and calcium channel agonist Bay K8644. In vitro, TMCC inhibited aconitine-induced increases in INa and ICa,L. These results revealed that TMCC inhibited aconitine-induced arrhythmias through effects on INa and ICa,L.

Complementary vascular-protective actions of magnesium and taurine: a rationale for magnesium taurate.
            (McCarty, 1996) Download
By a variety of mechanisms, magnesium functions both intracellularly and extracellularly to minimize the cytoplasmic free calcium level, [Ca2+]i. This may be the chief reason why correction of magnesium deficiency, or induction of hypermagnesemia by parenteral infusion, exerts antihypertensive, anti-atherosclerotic, anti-arrhythmic and antithrombotic effects. Although the amino acid taurine can increase systolic calcium transients in cardiac cells (and thus has positive inotropic activity), it has other actions which tend to reduce [Ca2+]i. Indeed, in animal or clinical studies, taurine lowers elevated blood pressure, retards cholesterol-induced atherogenesis, prevents arrhythmias and stabilizes platelets--effects parallel to those of magnesium. The complex magnesium taurate may thus have considerable potential as a vascular-protective nutritional supplement, and might also be administered parenterally, as an alternative to magnesium sulfate, in the treatment of acute myocardial infarction as well as of pre-eclampsia. The effects of magnesium taurate in diabetes deserve particular attention, since both magnesium and taurine may improve insulin sensitivity, and also may lessen risk for the micro- and macrovascular complications of diabetes.

Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics.
            (Moloney et al., 2010)  Download
Type 1 diabetics have a well-recognised risk of accelerated cardiovascular disease. Even in the absence of clinical signs there are detectable abnormalities of conduit vessel function. Our group has previously reported reversal of endothelial dysfunction in diabetics with pravastatin. In young asymptomatic smokers, taurine supplementation has a beneficial impact on macrovascular function, assessed by FMD, and shows an up-regulation of nitric oxide from monocyte-endothelial cell interactions. We hypothesise that taurine supplementation reverses early endothelial abnormalities in young male type 1 diabetics, as assessed by applanation tonometry, brachial artery ultrasound and laser Doppler fluximetry. Asymptomatic, male diabetics (n=9) were scanned prior to treatment and then randomised in a double-blind cross-over fashion to receive either 2 weeks placebo or taurine. Control patients (n=10) underwent a baseline scan. Assessed diabetics had detectable, statistically significant abnormalities when compared with controls, in both arterial stiffness (augmentation index) and brachial artery reactivity (FMD). Both of these parameters were returned to control levels with 2 weeks taurine supplementation. In conclusion, 2 weeks taurine supplementation reverses early, detectable conduit vessel abnormalities in young male diabetics. This may have important implications in the long-term treatment of diabetic patients and their subsequent progression towards atherosclerotic disease.

Role of osmoregulation in the actions of taurine
            (Schaffer et al., 2000) Download
Taurine regulates an unusual number of biological phenomena, including heart rhythm, contractile function, blood pressure, platelet aggregation, neuronal excitability, body temperature, learning, motor behavior, food consumption, eye sight, sperm motility, cell proliferation and viability, energy metabolism and bile acid synthesis. Many of these actions are associated with alterations in either ion transport or protein phosphorylation. Although the effects on ion transport have been attributed to changes in membrane structure, they could be equally affected by a change in the activity of the affected transporters. Three common ways of altering transporter activity is enhanced expression, changes in the phosphorylation status of the protein and cytoskeletal changes. Interestingly, all three events are altered by osmotic stress. Since taurine is a key organic osmolyte in most cells, the possibility that the effects of taurine on ion transport could be related to its osmoregulatory activity was considered. This was accomplished by comparing the effects of taurine, cell swelling and cell shrinkage on the activities of key ion channels and ion transporters. The review also compares the phosphorylation cascades initiated by osmotic stress with some of the phosphorylation events triggered by taurine depletion or treatment. The data reveal that certain actions of taurine are probably caused by the activation of osmotic-linked signaling pathways. Nonetheless, some of the actions of taurine are unique and appear to be correlated with its membrane modulating and phosphorylation regulating activities.

Host defense--a role for the amino acid taurine
            (Stapleton et al., 1998)  Download
Taurine (2-aminoethane sulphonic acid), a ubiquitous beta-amino acid is conditionally essential in man. It is not utilized in protein synthesis but found free or in some simple peptides. Derived from methionine and cysteine metabolism, taurine is known to play a pivotal role in numerous physiological functions. Some of the roles with which taurine has been associated include osmoregulation, antioxidation, detoxification and stimulation of glycolysis and glycogenesis. Intracellular taurine is maintained at high concentrations in a variety of cell types and alteration of cell taurine levels is difficult. The role of taurine within the cell appears to be determined by the cell type. Recent research has determined a regulatory role for taurinechloramine, the product formed by the reaction between taurine and neutrophil derived hypochlorous acid on macrophage function. Plasma taurine levels are also high, although decreases are observed in response to surgical injury and numerous pathological conditions including cancer and sepsis. Supplementary taurine replenishes decreased plasma taurine. Although commonly used as a dietary supplement in the Far East, the potential advantages of dietary taurine supplementation have not as yet been fully recognized in the Western World; this is an area which could prove to be beneficial in the clinical arena.

Calcium paradox in newborn and adult guinea-pig hearts: changes in intracellular taurine and the effects of extracellular magnesium.
            (Suleiman and Chapman, 1993) Download
The isolated hearts of adult and neonatal guinea-pigs have been compared for changes in intracellular amino acids during calcium depletion and the loss of cellular proteins on calcium repletion. Taurine, in freshly excised ventricles of neonatal guinea-pig heart, at 10.5 +/- 0.5 mmol (kg wet weight)-1 (n = 5) is less than in the adult heart (13.0 +/- 0.6 mmol (kg wet weight)-1 (n = 5)) but still is the most abundant amino acid free in the sarcoplasm. A marked loss of tissue taurine in both neonatal and adult hearts (a fall to 3.5 +/- 0.25 mmol (kg wet weight)-1 in neonatal and 4.9 +/- 0.6 mmol (kg wet weight)-1 in adult hearts after 10 min) was induced by perfusion with Ca, Mg-free Tyrode solution. A fall in several of the alpha-amino acids was also seen during this manoeuvre. On reperfusion with normal Tyrode solution, a marked release of proteins (lactate dehydrogenase, creatine kinase and myoglobin) was observed, which showed a similar time course in both types of heart. Elevation of [Mg]o during calcium depletion reduced protein loss on calcium repletion in both neonatal and adult guinea-pig hearts. This effect was consistent with an effect of Mg2+ on the rise of [Na]i. A second effect of [Mg]o was to shift the time to peak protein loss, an effect greater in neonatal hearts and more pronounced for the proteins with larger molecular weight (lactate dehydrogenase > creatine kinase > myoglobin). This latter effect of Mg2+ would seem not to be due to an effect on capillary permeability because the presence of bovine serum albumin in the perfusate failed to produce a similar effect. Neonatal and adult guinea-pig hearts show a similar sensitivity to the calcium paradox and similar changes in tissue taurine during calcium depletion, and therefore contrast with rat and rabbit heart.

Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study.
            (Sun et al., 2016) Download
Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to lower blood pressure (BP) in hypertensive animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human hypertension or prehypertension, a key stage in the development of hypertension. In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on BP and vascular function in prehypertension. We randomly assigned 120 eligible prehypertensive individuals to receive either taurine supplementation (1.6 g per day) or a placebo for 12 weeks. Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H2S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H2S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment upregulated the expression of hydrogen sulfide-synthesizing enzymes and reduced agonist-induced vascular reactivity through the inhibition of transient receptor potential channel subtype 3-mediated calcium influx in human and mouse mesenteric arteries. In conclusion, the antihypertensive effect of chronic taurine supplementation shows promise in the treatment of prehypertension through improvement of vascular function.

Low cardiovascular risks in the middle aged males and females excreting greater 24-hour urinary taurine and magnesium in 41 WHO-CARDIAC study populations in the world.
            (Yamori et al., 2010) Download
BACKGROUND:  Since taurine (T) administration was proven to decrease blood pressure (BP) and stroke mortality in stroke-prone spontaneously hypertension rates (SHRSP) in the 1980's and our WHO-coordinated CARDIAC (Cardiovascular Diseases and Alimentary Comparison) Study demonstrated that among 5 diet-related factors, namely total cholesterol (T-Cho), body mass index (BMI), sodium (Na), magnesium (M), and T to creatinine (Cr) ratio in 24-hour urine (24U), both T/Cr and M/Cr were inversely related to coronary heart disease mortalities in males and females and T/Cr was inversely related to stroke mortalities in males and females. We further analyzed the associations of individual T/Cr and M/Cr levels to cardiovascular risks in the present study. METHOD:  From WHO-CARDIAC Study populations, 61 populations of 25 countries in the world, Japanese populations with obviously higher 24U T excretion because of their common fish eating custom and the other populations in which both data of T and M were not available were excluded and the data of 3960 individuals from 41 WHO-CARDIAC Study populations were used for the following analyses. RESULTS:  The means of 24U T/Cr and M/Cr ratios in total individual data were 639.4 and 82.8, respectively. The average of BMI, systolic and diastolic blood pressure (SBP, DBP), T-Cho and atherogenic index (AI) in the individuals with more than the means of T/Cr or M/Cr were significantly lower than those of individuals with less than the means. The CARDIAC Study participants were divided into the following 4 groups by these means: A (T/Cr and M/Cr > or = mean), B (T/Cr > or = mean, M/Cr < mean), C (T/Cr < mean, M/Cr > or = mean), D (T/Cr and M/Cr < mean). The group A showed significantly lower values compared with the group D in BMI, SBP, DBP, T-Cho, and AI. CONCLUSIONS:  Cardiovascular risks were proven to be highly significantly lower in individuals who were excreting both 24U T and M, more than the averages despite differences in ethnicity and genetic background. Since T and M are biomarkers for seafood, vegetables, soy, nuts, milk, etc., dietary custom to eat these food sources could be recommended for cardiovascular disease prevention.

Taurine Intake with Magnesium Reduces Cardiometabolic Risks.
            (Yamori et al., 2017) Download
WHO-CARDIAC (Cardiovascular Diseases and Alimentary Comparison) Study revealed the quintile analyses of 24-h urinary (24 U) taurine (T) and magnesium (Mg) excretions were inversely related with cardiometabolic risks (CMR) such as obesity, hypertension and hypercholesterolemia in 50 population samples in the world. To exclude the influence of ethnicity in the study, 24 U T and Mg excretions were analyzed for the association with CMR in one ethnicity, Japanese population.24 U T/creatinine (C) ratios were divided into 5 quintiles and the ratios of Japanese to the total of each quintile were analyzed from CARDIAC Study samples. The highest 24 U T quintile consisted of 60% Japanese, indicating high seafood consumption in Japanese.Over 600 Japanese aged 30-79 were invited to a health examination for blood pressure measurement and for fasting blood and 24 U samplings. Tertile analysis of 24 U T/C ratios in relation to CMR indicated the third tertile had significantly higher HDL cholesterol, 24 U potassium (K) and 24 U salt than the first (lowest) tertile. Tertile analysis of 24 U Mg/C ratios indicated the third tertile had significantly lower body mass index and significantly higher folic acid, 24 U isoflavones, K and salt than the first tertile after age and gender adjustment. The third tertile of both T/C and Mg/C had significantly lower body mass index, LDL/HDL and Na/K ratios, and significantly higher HDL cholesterol and folic acid than the first tertile, indicating seafood eaters taking Mg rich diets had lower risks of obesity, atherosclerosis, hypertension and higher folic acid, beneficial for healthy longevity.

 


References

Birdsall, TC (1998), ‘Therapeutic applications of taurine.’, Altern Med Rev, 3 (2), 128-36. PubMed: 9577248
EDREN. (2020). Fluid and electrolyte replacement in renal failure. Retrieved from http://edren.org/ren/handbook/unithdbk/fluid-and-electrolyte-replacement-in-renal-failure/
Franconi, F., et al. (1995), ‘Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation’, Am J Clin Nutr, 61 (5), 1115-19. PubMed: 7733037
Jia, F, et al. (2008), ‘Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus.’, J Neurosci, 28 (1), 106-15. PubMed: 18171928
Katakawa, M, et al. (2016), ‘Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats.’, Hypertens Res, 39 (12), 848-56. PubMed: 27412799
Lou, J, et al. (2018), ‘Taurine-magnesium coordination compound, a potential anti-arrhythmic complex, improves aconitine-induced arrhythmias through regulation of multiple ion channels.’, Toxicol Appl Pharmacol, 356 182-90. PubMed: 30125596
McCarty, MF (1996), ‘Complementary vascular-protective actions of magnesium and taurine: a rationale for magnesium taurate.’, Med Hypotheses, 46 (2), 89-100. PubMed: 8692051
Moloney, M. A., et al. (2010), ‘Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics’, Diab Vasc Dis Res, 7 (4), 300-10. PubMed: 20667936
Schaffer, S., K. Takahashi, and J. Azuma (2000), ‘Role of osmoregulation in the actions of taurine’, Amino Acids, 19 (3-4), 527-46. PubMed: 11140357
Stapleton, PP, et al. (1998), ‘Host defense--a role for the amino acid taurine’, JPEN J Parenter Enteral Nutr, 22 (1), 42-48. PubMed: 9437654
Suleiman, MS and RA Chapman (1993), ‘Calcium paradox in newborn and adult guinea-pig hearts: changes in intracellular taurine and the effects of extracellular magnesium.’, Exp Physiol, 78 (4), 503-16. PubMed: 8398104
Sun, Q, et al. (2016), ‘Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study.’, Hypertension, 67 (3), 541-49. PubMed: 26781281
Yamori, Y, et al. (2010), ‘Low cardiovascular risks in the middle aged males and females excreting greater 24-hour urinary taurine and magnesium in 41 WHO-CARDIAC study populations in the world.’, J Biomed Sci, 17 Suppl 1 S21. PubMed: 20804596
Yamori, Y, et al. (2017), ‘Taurine Intake with Magnesium Reduces Cardiometabolic Risks.’, Adv Exp Med Biol, 975 Pt 2 1011-20. PubMed: 28849518