Abstract: Plasma and platelet levels of 18 amino acids were measured in 29 outpatients (mean age ± SD 4741 ± 1085 years; 14 F, 15 M) affected by major depression (DSM IV) and in 28 healthy volunteers (mean age 4246 ± 1419 years; 12 F, 16 M) Plasma and platelet levels of amino acids tended to be higher in depressed patients than in healthy controls In particular, glutamate, taurine and lysine plasma levels and aspartate, serine and lysine platelet levels were significantly higher Tryptophan/large neutral amino acids ratio (trp/LNAAs) was significantly lower in depressed patients Fluvoxamine treatment did not influence plasma and platelet levels of amino acids or trp/LNAAs ratio

Abstract: Taurine is an essential amino acid during fetal life and appears to be vital for the growth of the fetus and for the development of the CNS. In intrauterine growth restriction (IUGR), fetal plasma concentrations of taurine are reduced, and we tested the hypothesis that this is caused by altered placental transport of taurine. Syncytiotrophoblast microvillous membrane (MVM) and basal membrane (BM) vesicles were isolated from control (fetal weight, 3068+/-191 g; gestational age, 37.0+/-0.7 wk; n=13) and IUGR pregnancies (fetal weight, 1724+/-118 g; gestational age, 35.8+/-0.7 wk; n=11). Uptake of [3H]taurine (0.5 microM) was studied at 22 degrees C using rapid filtration techniques. Sodium stimulated taurine uptake 35-fold in MVM, confirming Na+-dependent transport in this membrane. A Na+-dependent taurine transport could also be demonstrated in BM; however, the activity was only 6% of that in MVM. Na+-independent transport activities were similar in MVM and BM. In IUGR, MVM Na+-dependent taurine transport was reduced by 34% (p < 0.05), whereas Na+-independent uptake was unaltered. In contrast to MVM, Na+-dependent taurine uptake in BM was unaffected by IUGR, whereas Na+-independent transport was decreased by 33% (p < 0.05). The highly polarized distribution of the Na+/taurine cotransporter to the MVM in conjunction with similar Na+-independent transport rates for taurine in MVM and BM provides the basis for net taurine flux from the mother to the fetus. These data suggest that the low plasma concentrations of taurine in IUGR fetuses are caused by a reduced activity of placental taurine transporters.

Abstract: 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. (Alt Med Rev 1998;3(2):128-136)

Abstract: An isocaloric low-protein (LP) diet (8% instead of 20% in controls) given to dams during gestation reduces the fractional insulin release of stimulated fetal islets. The LP diet lowers the plasma concentration of taurine in both pregnant rats and their fetuses. This study reports the effect of taurine on the in vitro release of insulin from control and LP fetal islets. Direct stimulation with taurine, methionine or leucine increased the release of insulin from control islets. Nevertheless, no effect on LP islets was observed with either taurine or methionine. The release of insulin from LP islets was reduced with leucine. The in vitro addition of taurine (0. 3 or 3 mM) to the culture medium increased the release of insulin from the control islets in response to arginine or leucine, but it did not restore the reduced responsiveness of LP islets to these amino acids. When 2.5% taurine was added to the drinking water of control or LP dams (groups C+T and LP+T) throughout gestation, the concentration of taurine increased in the serum of dams and fetuses of both groups. The release of insulin from the LP+T fetuses was restored to control levels when stimulated with taurine, methionine, leucine or arginine. In conclusion, taurine stimulated control fetal islets in vitro, but failed to do so in LP islets. However, the addition of taurine to the diet of LP dams restored to normal the release of insulin from LP fetal islets, indicating the importance of taurine during development for a normal fetal beta cell function.

Abstract: 1. Taurine has recently been known to protect against ischemia and heart failure. Taurine possesses plenty of actions on the ion channels and transports, but is very non-specific. 2. Taurine may directly and indirectly help to regulate the [Ca]i level by modulating the activity of the voltage-dependent Ca2+ channels (also dependent on [Ca]i/[Ca]o), by regulation of Na+ channels, and secondly via Na-Ca exchange and Na(+)-taurine cotransport. 3. Taurine can prevent the Ca2+ ([Ca]o or [Ca]i)-induced cardiac functions. 4. Therefore, it seems possible that taurine could exert the potent cardioprotective actions even under the condition of low [Ca]i levels as well as under the Ca2+ overload condition. 5. The electrophysiological actions of taurine on cardiomyocytes, smooth muscle cells, and neurons from recent studies are summarized.

Abstract: 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.

Abstract: In vivo cysteine metabolism during the inflammatory state has been studied minimally. We investigated cysteine metabolism (i.e. taurine, sulfate and glutathione formation) using a single dose of [ 35 S] cysteine in septic rats that had been injected with live Escherichia coli into the tail vein and in control, pair-fed rats. Cysteine metabolites were separated by ion exchange chromatography, and radioactivity was counted in the different fractions. Radioactivity incorporated in tissue proteins was also measured after protein precipitation. [ 35 S]Sulfate production was significantly lower in septic rats than in pair-fed rats. [ 35 S]Taurine contents were significantly lower only in kidneys, spleen and gastrointestinal tract of septic rats. The higher production of [ 35 S] taurine in the livers (the major site of taurine production) of septic rats could have a protective effect against oxidation. Glutathione concentrations were also significantly greater in liver, spleen, kidneys and gastrocnemius muscle of septic rats, presumably in order to combat oxidative stress induced by sepsis. [ 35 S]Cysteine incorporation in glutathione was significantly higher in spleen and kidneys but not in liver of septic rats compared to pair-fed rats. This could be explained by the fact that, in liver, a greater amount of labeled glutathione had been utilized for host defense, or by a high level in glutathione turnover. Finally, [ 35 S]cysteine incorporation into protein, in septic rats, was significantly greater than in pair-fed rats in spleen, lung and particulary in whole plasma proteins other than albumin, which mainly represent the acute-phase proteins. These data suggest an increased requirement for cysteine during sepsis in rats.

Abstract: Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not to affect the urinary excretion of taurine (a non-invasive marker of liver damage), levels of serum and liver taurine were markedly raised in animals receiving alcohol + taurine compared to animals given taurine alone. The ethanol-inducible form of cytochrome P-450 (CYP2E1) was significantly induced by alcohol; the activity was significantly lower than controls and barely detectable in animals fed the liquid alcohol diet containing taurine. In addition, alcohol significantly increased homocysteine excretion into urine throughout the 28 day period of ethanol administration; however, taurine did not prevent this increase. There was evidence of slight cholestasis in animals treated with alcohol and alcohol + taurine, as indicated by raised serum bile acids and alkaline phosphatase (ALP). The protective effects of taurine were attributed to the potential of bile acids, especially taurine conjugated bile acids (taurocholic acid) to inhibit the activity of some microsomal enzymes (CYP2E1). These in vivo findings demonstrate for the first time that hepatic steatosis and lipid peroxidation, occurring as a result of chronic alcohol consumption, can be ameliorated by administration of taurine to rats.

Abstract: One of the hallmarks of apoptosis is cell shrinkage which appears to be important for cell death. The mechanisms mediating cell volume decrease have, however, not been addressed. Mechanisms employed by swollen cells to decrease their cell volume include activation of ion transport pathways, such as ion channels and KCl cotransport, and release of cellular osmolytes, such as taurine, sorbitol, betaine and inositol. The present study has been performed to test for release of taurine. To this end Jurkat human T-lymphocytes were loaded with [3H]taurine and apoptotic cell death induced by triggering the Fas(CD95) receptor with monoclonal crosslinking antibody. Triggering the Fas(CD95) receptor led to a release of 60±5% of cellular taurine within 90 min. The release did not occur prior to 45 min. The release coincided with cell shrinkage as evidenced from forward scatter in FACS analysis and preceeded DNA fragmentation according to propidium iodide staining. The delay of taurine release was not influenced by exchange of medium and thus was not due to extracellular accumulation of a stimulator. The Fas(CD95)-induced taurine release, cell shrinkage and DNA fragmentation were blunted by lowering of ambient temperature to 23°C. Following pretreatment of cells with Fas(CD95) antibody at 23°C rewarming led to rapid taurine release, cell shrinkage and DNA fragmentation, indicating that the temperature-sensitive step is distal to the mechanisms accounting for the delay. Osmotic cell swelling led to an immediate release of taurine. In conclusion, Fas(CD95) triggering leads to delayed taurine release through a temperature-sensitive mechanism.

Abstract: We had previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects, which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. In order to induce IBD, ethanolic TNBS was given to rats intracolonically. Then they received 500 mg/kg/day of taurine orally and were sacrificed one week after IBD induction. While ulceration and inflammation of distal colon with formation of granuloma in the vehicle-treated IBD rats two days after administration of TNBS were observed, treatment with taurine ameliorated colonic damage and decreased the incidence of diarrhea and adhesion. Also, colon weight as an index of tissue edema, which was markedly increased in the IBD rats, became significantly lower after taurine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased, compared with that of normal control. The taurine-treated animals significantly reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased both basal and formyl-methionyl leucyl phenylalanine-stimulated reactive oxygen generation from colonic tissue in the IBD rats. These results suggest that the administration of taurine reduce the inflammatory parameters in this IBD rat model by increasing defending capacity against oxidative damage.

Abstract: A reduction of resting chloride conductance (GCl) and a decrease of the voltage threshold for contraction are observed during aging in rat skeletal muscle. The above alterations are also observed in muscle of adult rat after taurine depletion. As lower levels of taurine were found by others in aged rats compared to young rats, we tested the hypothesis that a depletion of taurine may contribute to the alteration of the electrical and contractile properties we found in skeletal muscle during aging. This was accomplished by evaluating the potential benefit of a pharmacological treatment with the amino acid. To this aim 25-mo-old Wistar rats were chronically treated (2–3 mo) with taurine (1 g/kg p.o. daily) and the effects of such a treatment were evaluated in vitro on the passive and active membrane electrical properties of extensor digitorum longus muscle fibers by means of current-clamp intracellular microelectrode technique. Excitation-contraction coupling was also evaluated by measuring the voltage threshold for contraction with the intracellular microelectrode “point” voltage clamp method. In parallel muscle and blood taurine contents were determined by high-performance liquid chromatography. Taurine supplementation significantly raised taurine content in muscle toward that found in adult rats. Supplementation also significantly increased GCl vs. the adult value, in parallel the excitability characteristics (threshold current and latency) related to this parameter were ameliorated. The increase of GCl induced by taurine was accompanied by a restoration of the pharmacological sensitivity to the R(+) enantiomer of 2-(p-chlorophenoxy) propionic acid, a specific chloride channel ligand. In parallel also the protein kinase C-mediated modulation of the channel was restored; in fact the potency of 4-β-phorbol 12,13-dibutyrate in reducing GCl was lower in taurine-treated muscles vs. untreated aged, being rather similar to that observed in adult. The treatment also improved the mechanical threshold for contraction of striated fibers which in aged rats is shifted toward more negative potentials, moving it toward the adult values. Our results suggest that the reduction of taurine content could play a role in the alteration of electrical and contractile properties observed during aging. These findings may indicate a potential application of taurine in ensuring normal muscle function in the elderly.

Abstract: Objective: To evaluate the amino acid profile in a group of adolescents with anorexia nervosa, and to apply alternative ways of presenting and assessing results, so as to increase the information available for understanding the metabolic abnormalities developed in these patients. Design: Plasma amino acid concentrations of a random group of patients with anorexia nervosa compared with values obtained from a ‘healthy’ adolescent population. Setting: The study was performed at the tertiary children’s Hospital Sant Joan de Deu. Subjects: Female adolescents (n=92, age: 15±1.8 y) at diagnosis of anorexia nervosa. Reference values for amino acids were obtained from apparently healthy adolescents (by history and analytical data) who underwent presurgical analysis for minor operations. Interventions: Plasma amino acid concentrations were measured by ion exchange chromatography. Basic laboratory analysis, carnitine and IGF-I were also determined. Results: In anorexic patients plasma concentrations of taurine, asparagine, glutamine, glycine, methionine, phenylalanine, ornithine, and histidine were significantly higher than reference values (Mann-Whitney, P<0.01– 0.0001), whereas arginine and cystine were lower than our reference values (P<0.0001). Relative amino acid values (the molar fraction of the patient medians relative to control medians) were plotted. The ratios of some amino acids were significantly greater than those obtained from the reference population: Phe/Tyr (P<0.001), Met/Cys (P<0.0001), and Gly/Val (P<0.01). Conclusions: A trend to hyperaminoacidemia is a common feature in anorexia nervosa. Although absolute amino acid values cannot play a significant role in the assessment of nutritional status in this condition, the calculation of some ratios (Phe/Tyr, Met/Cys and Gly/Val) and the graphical representation of relative values may be useful. The plasma amino acid profile in anorexia nervosa is different from those of other severe malnutrition states, showing a marasmic pattern of balanced protein–energy undernutrition. Cystine and arginine may be considered limiting amino acids in this disease, and the consequences of their deficient concentrations for oxidative damage should be further evaluated. Sponsorship:D. Moyano was the recipient of a grant from the Hospital Sant Joan de Deu, Barcelona.

Abstract: The purpose of this study was to investigate the effect of taurine on human fetal brain neuron cell proliferation and differentiation using a glial-free, pure cerebral neuronal culture grown in a serum-free environment. We found that taurine was necessary for neuronal survival and neurite extension. Taurine, on the other hand, has a trophic effect on the human fetal brain cell, promoting both proliferation and differentiation. Results showed that DNA synthesis of the neurons was increased in a dose-dependent manner when neurons were cultured in the medium containing taurine (100–6400 μM). The protein content of neuronal cells was also significantly increased in the neurons treated with taurine as compared to the control. At day 15, the expression of neuron-specific enolase (NSE) was only detected in the neurons cultured in the medium containing taurine. These results establish taurine as a putative human fetal brain neurontrophic factor in the process of human brain development.

Abstract: Taurine, 2-amino ethanesulfonic acid, is the major free intracellular amino acid present in many tissues and plays an important role in lipid metabolism such as that of bile acid conjugation for fat absorption. The effect of taurine on the serum cholesterol level in normal rats was investigated. Taurine enhanced the serum HDL-cholesterol concentration in a dose-dependent manner without any change in total cholesterol.

Abstract: The effects of glutamine, glycine and taurine on the development of bovine zygotes derived from IVM/IVF were determined using a protein-free chemically defined medium. After the cumulus cells were removed at 18 hr post-insemination, the presumptive zygotes were cultured for 4 or 6 days (about 104 or 154 hr) under a gas atmosphere of 5% O2: 5% CO2: 90% N2. A modified synthetic oviduct fluid medium supplemented with 20 amino acids (1 mM glutamine, essential amino acids for basal medium Eagle and non-essential amino acids for minimum essential medium), insulin, and PVA was used as a basic medium (mSOFai). Omitting 1 mM glutamine from mSOFai did not affect the embryonic development after 4 and 6 days of culture. After 4 days of culture, no significant effects of glycine and taurine on the development of zygotes to the morula stage were observed. However, supplementation with glycine or taurine significantly (P < 0.05) affected, with no interaction, the embryonic development to blastocysts after 6 days of culture. Addition of 5 mM glycine and 2 or 10 mM taurine significantly (P < 0.05) increased the percentage of blastocysts. The mean cell number in the blastocysts was affected by the glycine level, and was increased by the addition of 10 mM glycine (P < 0.001). These results demonstrate that glycine and taurine in a chemically defined medium containing a group of essential and non-essential amino acids improve the development of bovine zygotes to the blastocyst stage under 5% O2.

Abstract: We previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. To induce IBD, rats were given ethanolic TNBS intracolonically. The rats then received 500 mg/kg/day of taurine per orally. The rats were sacrificed one week after IBD induction. Ulceration and inflammation of the distal colon with formation of granuloma in the vehicle-treated IBD rats after two days of administration of TNBS were observed. Treatment with 0.5 g/kg of taurine by the oral route ameliorated colonic damage and decreased the incidence of diarrhea and adhesions. Colon weight (an index of tissue edema) was markedly increased in the IBD rats after administration of TNBS, but was significantly lower after taurine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased compared with that of the control. The taurine-treated animals showed reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased basal and formyl-methionyl leucyl phenylalanine (FMLP) stimulated reactive oxygen generation in colonic tissue of the IBD rat compared with vehicle treatment after one week. These results suggest that administration of taurine reduced the inflammatory parameters in this rat model of IBD by increasing the defenses against oxidative insult.

Abstract: Biotransformation of cerivastatin was investigated in mice, rats, and dogs in vivo using the 14C-labeled drug. Marked species differences exist, both in pathways and extent of cerivastatin metabolism. Unchanged drug, together with its lactone, predominates in dog plasma and represents 40% of the dose in the excreta, whereas in rat bile they account for approximately 10% of the dose. In mice, the drug is metabolized rapidly and almost completely. Biotransformation of cerivastatin occurs by three distinct phase I routes and by phase II conjugation with sugar-type moieties and taurine. Phase I routes are demethylation of the pyridinyl methyl ether, beta-oxidation of the 3,5-dihydroxy acid side chain, and reductive removal of the side chain 3-hydroxy group. In dogs, demethylation is the dominating phase I biotransformation. Phase II conjugation is equally important. In dog bile, different regioisomeric drug glucuronides and the benzylic glucuronide and glucoside conjugate of the demethylated drug were found. In rats, besides demethylation, beta-oxidation of the dihydroxy acid side chain-followed by reductive removal of the 5-hydroxy group-is the major reaction. The resulting pentenoic acid derivatives are observed in plasma and liver homogenate. These metabolites are subsequently conjugated with taurine and excreted in the bile. This metabolic sequence is also important in mice. Furthermore, only in mice, cerivastatin is subject to reductive removal of the 3-hydroxy group, together with demethylation. The 5-hydroxyheptenoic acids formed predominate in plasma and liver homogenate, whereas the corresponding taurine conjugates are excreted in the bile.

Abstract: Two precursors of taurine have been studied: cysteamine and hypotaurine. Cysteamine has been quantified in genital secretions and found in follicular fluids of all species tested. On the contrary cysteamine was not detected (or traces) in tubal fluids of the same species. Addition of 50, 100 or 250 microM of cysteamine to the maturation medium used in the culturing of bovine oocytes did not improve the cleavage rate nor the embryo's developmental potential in vitro. Furthermore, at 250 microM, cysteamine seems to be toxic to the embryo. Addition of 0.5-1 mM hypotaurine to the bovine embryo culture medium improved significantly blastocyst production and quality. The respective roles of these 2 taurine precursors on maturation and embryo development are discussed.