Abstract: 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.

Abstract: Taurine (2-aminoethanesulphonic acid), a sulphur-containing amino acid, is found in most mammalian tissues Although it can be synthesized endogenously, the major source of taurine is from the diet Taurine was found to exhibit diverse biological actions, including protection against ischemia-reperfusion injury, modulation of intracellular calcium concentration, and antioxidant, antiatherogenic and blood pressure-lowering effects The present review will address the potential beneficial actions of taurine in congestive heart failure, hypertension, ischemic heart disease, atherosclerosis and diabetic cardiomyopathy There is a wealth of experimental information and some clinical evidence available in the literature suggesting that taurine could be of benefit in cardiovascular disease of different etiologies However, double-blind long-term clinical trials need to be conducted before taurine can be unequivocally recommended as a nutritional intervention for the prevention and/or treatment of cardiovascular disease

Abstract: Tamoxifen is a selective oestrogen receptor modulator widely used in the treatment of breast cancer. Tamoxifen potentially affects mitochondrial functions as it acts as an uncoupling agent and a powerful inhibitor of mitochondrial electron transport chain. There is concern for the deleterious effects of tamoxifen. Taurine is known to have membrane stabilizing and antioxidant properties. We studied effect of taurine pre-treatment on the toxicity of tamoxifen in mouse liver mitochondria focusing specifically on the redox cycle biomarkers. Tamoxifen caused a significant rise in the mitochondrial lipid peroxidation, protein carbonyl content and superoxide radical generation. There was a significant change in the mitochondrial thiol profile in the tamoxifen-treated animals. Pre-treatment of mice with taurine (100 mg/kg) markedly lowered mitochondrial lipid peroxidation, protein carbonyl content and superoxide radical generation. It also restored decreased enzymatic and non-enzymatic antioxidants of mitochondria. It is suggested that taurine has a potential role in ameliorating tamoxifen-induced mitochondrial toxicity, and the protection is afforded either by reversing the decline of antioxidants or by the direct free radical-scavenging activity.

Abstract: An in vivo study of intracerebral rat glioma using proton-localized NMR spectroscopy showed important modifications of the spectra in the tumor as compared with the contralateral brain To carry out the assignment of the resonances of the glioma spectra, tumoral and normal rat brain tissues were studied in vivo, ex vivo, and in vitro by one-dimensional and two-dimensional proton spectroscopy N-Acetylaspartate was found at an extremely low level in the glioma The change of peak ratio total creatine/32 ppm peak was found to be due to a simultaneous decrease of the total creatine content and an increase of the 32 ppm peak The 32 ppm resonance in the glioma spectra has been shown to originate from choline, phosphocholine, glycerophosphocholine, taurine, inositol, and phosphoethanolamine The increase of the 32 ppm peak in the glioma was found to result from the increase of taurine and phosphoethanolamine contents The peak in the 13 ppm region of the glioma spectra was due to both lactate and mobile fatty acids Moreover, two-dimensional spectroscopy of excised tissues and extracts showed the presence of hypotaurine only in the tumor

Abstract: This study was conducted to investigate taurine deficiency and the ability of taurine biosynthesis in both juvenile Japanese flounder (JF) and juvenile common carp (CC) in vivo using low taurine level diets. Three different taurine level diets were prepared by the supplementation of taurine to the basal composition (JF – 0, 0.5 and 1.5% in JF; CC – 0, 1, 3% in CC). The final average body weight and feed efficiency of JF fed the JF – 1.5% was significantly higher than those of fish fed on the JF – 0%. On the other hand, no significant difference was observed in CC fed with CC – 0, 1, and 3% diets. The taurine retention rate was negative in the case of JF-fed with the taurine-free supplement (JF – 0%). On the other hand, the taurine retention rate was about 280% in the case of CC-fed with the taurine-free supplement (CC – 0%). These findings indicate that while taurine is essential for growth of JF, it is not essential for the growth of CC.

Abstract: Brain edema in hepatic encephalopathy has been associated with circulating ammonia that is metabolized to glutamine. We measured alterations in blood chemistry and brain regional specific gravity and ion and amino acid contents in models of simple hyperammonemia and liver failure induced by daily administrations of ammonium acetate (AAc) or thioacetamide (TAA), respectively. Serum and brain ammonia increased to similar levels (200 and 170% of control, respectively) in both experimental groups. Serum transaminase activities increased 10-fold in animals injected with TAA but were unchanged in animals given AAc injections. In both experimental groups glutamine was elevated in cerebral white matter, cerebral gray matter, and basal ganglia, whereas brain tissue specific gravity decreased in all brain regions, indicating edema formation. In the AAc group, we observed a decrease in glutamate and taurine contents concomitant with the development of brain edema. In these animals, cerebral gray matter specific gravity and taurine contents returned to control levels 24 h after the third AAc injection. TAA-injected animals demonstrated similar decreases in brain tissue specific gravity, whereas glutamine, glutamate, and taurine contents were all elevated. During hepatic encephalopathy, ammonia-induced changes in brain amino acid content may contribute to brain edema development.

Abstract: This study was conducted to investigate the effect of dietary taurine and cholyltaurine (C-tau) on growth and body composition of juvenile red sea Bream Pagrus major. Semi-purified casein-based diets supplemented with 0 (control diet), 0.1, 0.3, 0.5 and 0.7% taurine and 0.5% C-tau were fed to red sea bream (average body weight 4.7g) for 6 weeks at 20°C. The growth and feed efficiency were the lowest in fish fed the control diet. Taurine supplementation improved the growth and feed efficiency of fish dose-dependently, and the taurine requirement was estimated as 0.52% in terms of optimizing growth and 0.48% in terms of optimizing feed efficiency. Taurine content in the whole body and liver increased with the dietary taurine level. Supplemental C-tau at the 0.5% level had limited effects on the growth and no effect on body taurine, biliary bile salt and liver fat contents. From these results it can be inferred that the optimal dietary taurine requirement of juvenile red sea bream is 0.5% on a dry weight basis, and that the supplementation of taurine in the diet not only improves the growth but also increases hepatic lipid levels of red sea bream juveniles.

Abstract: Although considerable evidence supports a role for amino acids in transient global cerebral ischemia and permanent focal cerebral ischemia, effects of transient focal cerebral ischemia on the extracellular concentrations of amino acids have not been reported. Accordingly, our study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, GABA, taurine, glutamine, alanine, and phosphoethanolamine in the striatum of transient focal cerebral ischemia, as evidence to support their pathogenic roles. Focal ischemia was induced using the middle cerebral artery occlusion model, with no need for craniotomy. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. One hour of middle cerebral artery occlusion followed by recirculation caused neuronal damage that was common in the frontoparietal cortex and the lateral segment of the caudate nucleus. During 1 h of ischemia, the largest increase occurred for GABA and moderate increases were observed for taurine, glutamate, and aspartate. Alanine, which is a nonneuroactive amino acid, increased little. After recirculation, the levels of glutamate and aspartate reverted to normal baseline values right after reperfusion. Despite these rapid normalizations, neuronal damage occurred. Therefore, uptake of excitatory amino acids can still be restored after 1 h of middle cerebral artery occlusion, and tissue damage occurs even though high extracellular levels of glutamate are not maintained.

Abstract: A variety of physiological and pathological factors induce cellular swelling in the brain Changes in cell volume activate several types of ion channels, which mediate the release of inorganic and organic osmolytes and allow for compensatory cell volume decrease Volume-regulated anion channels (VRAC) are thought to be responsible for the release of some of organic osmolytes, including the excitatory neurotransmitters glutamate and aspartate In the present study, we compared the in vivo properties of the swelling-activated release of glutamate, aspartate, and another major brain osmolyte taurine Cell swelling was induced by perfusion of hypoosmotic (low [NaCl]) medium via a microdialysis probe placed in the rat cortex The hypoosmotic medium produced several-fold increases in the extracellular levels of glutamate, aspartate and taurine However, the release of the excitatory amino acids differed from the release of taurine in several respects including: (i) kinetic properties, (ii) sensitivity to isoosmotic changes in [NaCl], and (iii) sensitivity to hydrogen peroxide, which is known to modulate VRAC Consistent with the involvement of VRAC, hypoosmotic medium-induced release of the excitatory amino acids was inhibited by the anion channel blocker DNDS, but not by the glutamate transporter inhibitor TBOA or Cd2+, which inhibits exocytosis In order to elucidate the mechanisms contributing to taurine release, we studied its release properties in cultured astrocytes and cortical synaptosomes Similarities between the results obtained in vivo and in synaptosomes suggest that the swelling-activated release of taurine in vivo may be of neuronal origin Taken together, our findings indicate that different transport mechanisms and/or distinct cellular sources mediate hypoosmotic medium-induced release of the excitatory amino acids and taurine in vivo

Abstract: Objective: Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. Its taurine conjugate, TUDCA, is a cPKCα agonist. We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKCα-/PKA-dependent mechanisms in taurolithocholic acid (TLCA)-induced cholestasis. Methods: In perfused rat liver, bile flow was determined gravimetrically, organic anion secretion spectrophotometrically, lactate dehydrogenase (LDH) release enzymatically, cAMP response-element binding protein (CREB) phosphorylation by immunoblotting, and cAMP by immunoassay. PKC/PKA inhibitors were tested radiochemically. In vitro phosphorylation of the conjugate export pump, Mrp2/Abcc2, was studied in rat hepatocytes and human Hep-G2 hepatoma cells. Results: In livers treated with TLCA (10 μmol/l)+TUDCA (25 μmol/l), combined inhibition of cPKC by the cPKC-selective inhibitor Go6976 (100 nmol/l) or the non-selective PKC inhibitor staurosporine (10 nmol/l) and of PKA by H89 (100 nmol/l) reduced bile flow by 36% (p S -glutathione, by 31% (p Conclusion: UDCA conjugates exert their anticholestatic action in bile acid-induced cholestasis in part via cooperative post-translational cPKCα-/PKA-dependent mechanisms. Hepatocellular Mrp2 may be one target of bile acid-induced kinase activation.

Abstract: The effects of dietary taurine on the experimental colitis induced by dextran sulfate sodium (DSS) in mice were evaluated. C57BL/6 female mice were given 3% DSS in drinking water for 5 d to induce acute colitis. Taurine at 2% was added to the drinking water 5 d before and during the DSS-treatment to investigate its preventive effect. Taurine supplementation significantly attenuated the weight decrease, diarrhea severity, colon shortening, and the increase in the colonic tissue myeloperoxidase activity induced by DSS. Taurine also significantly inhibited the increase in the expression of a pro-inflammatory chemokine, macrophage inflammatory protein 2 (MIP-2), but not of interleukin (IL)-1β or tumor necrosis factor (TNF)-α mRNA. Furthermore, taurine significantly protected the intestinal Caco-2 cell monolayers from the damage by macrophage-like THP-1 cells in an in vitro coculture system. These results suggest that taurine prevented DSS-induced colitis partly in association with (1) its inhibitory effects on the secretion of MIP-2 from the intestinal epithelial cells and on the infiltration of such inflammatory cells as neutrophils and (2) its cytoprotective functions on the epithelial barrier from the direct toxicity of DSS and from the inflammatory cell-induced injury.

Abstract: The present study was conducted to investigate whether the conditionally essential amino acid taurine could play any protective role against the potent neurotoxin cadmium (Cd)-induced oxidative impairment in mice brain. Cd administration in the form of CdCl(2 )(at a dose of 4 mg kg(-1) body weight for 3 days, orally) increased the intracellular accumulation of metallic Cd, reactive oxygen species and super oxide radicals. The toxin also augmented the extent of lipid peroxidation, protein carbonylation and the levels of glutathione disulfide. Activities of the antioxidant enzymes and the levels of reduced glutathione as well as total thiols have been significantly decreased due to Cd exposure. In addition, the toxin also caused significant DNA degradation (as evidenced from DNA smearing and diphenylamine reaction). Oral administration of taurine (at a dose of 100 mg kg(-1) body weight for 5 days) was found to be very effective in the prevention of Cd-induced oxidative impairment in the brain tissue of experimental mice. In addition, taurine treatment could also prevent the reduction in the in vivo antioxidant power linearly up to a dose of 100 mg kg(-1) body weight. The preventive role of taurine against Cd-induced cerebral oxidative damage was supported by the observation under scanning electron microscope as well as histological examination of brain segments. To validate the experimental results, a well-known water soluble antioxidant, vitamin C, was used as the positive control in the study. In all, the results suggest that taurine plays a beneficial role against Cd-induced cerebral oxidative stress.

Abstract: Ultrastructural changes in hepatocytes after taurine treatment in CCl4 induced liver injury

Abstract: The purpose of this study was to investigate whether taurine ameliorate the diabetic retinopathy, and to further explore the underlying mechanisms. The Sprague-Dawley rats were injected with streptozotocin to establish experimental diabetic model, then fed without or with 1.2% taurine for additional 4–12 weeks. After that, the protective effects of dietary taurine supplementation on diabetic retinopathy were estimated. Our results showed that chronic taurine supplement effectively improved diabetic retinopathy as changes of histopathology and ultrastructure. The supplementation could not lower plasma glucose concentration (P > 0.05), but caused an elevation in taurine content and a decline in levels of glutamate and γ-aminobutyric acid (GABA) in diabetic retina (P < 0.05). Moreover, chronic taurine supplementation increased glutamate transporter (GLAST) expression (P < 0.05), decreased intermediate filament glial fibrillary acidic protein (GFAP) and N-methyl-d-aspartate receptor subunit 1 (NR1) expression in diabetic retina (P < 0.05). These results demonstrated that chronic taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in rats.

Abstract: Melatonin, acting through its receptors, is involved in numerous physiological processes, including blood pressure (BP) regulation. In present study, the effect of melatonin inhibition on stress-induced hypertension was investigated. The hypertensive model consisted of male Sprague-Dawley rats subjected to electrical foot-shock combined with noise. Microinjection of melatonin (0.1 and 1.0 mmol/L) into the anterior hypothalamic area (AHA) produced a fall in BP in nomortensive rats and stress-induced hypertensive rats (SIHR). Luzindole (10 mmol/L), a competitive antagonist of melatonin MT1 and MT2 receptors, almost completely abolished the depressor effect of melatonin, the MT2 receptor-specific antagonist 4-phenyl-2-propionamidotetralin (10 mmol/L) partially blocked (by approximately 60%) the depressor effect of melatonin, whereas the MT3 receptor-selective antagonist prazosin (10 mmol/L) failed to antagonize the effects of melatonin. Brain microdialysis was performed in the AHA and the rostral ventrolateral medulla (RVLM). Melatonin and amino acids in the dialysate samples collected were detected by high-performance liquid chromatography combined with fluorescence detection. The results indicated that melatonin concentrations in the AHA were reduced in SIHR. Microinjection of melatonin into the AHA decreased glutamate release and increased GABA and taurine release in the RVLM, which were paralleled by a decrease in arterial pressure. The mRNA expression of MT2 in the AHA of SIHR was higher than that in normotensive control rats, whereas there was no significant difference in MT1 mRNA expressin between the two groups. The results of the present study suggest that both a decrease of melatonin and an increase in the MT2 receptor in the AHA are involved in the manifestation of stress-induced hypertension. Both MT1 and MT2 receptors participated in the antihypertensive effect of melatonin in the AHA. The antihypertensive effect of melatonin was related to the decreases in the excitatory amino acid glutamate and increases in the inhibitory amino acids taurine and GABA in the RVLM.

Abstract: Aims/hypothesis Events during fetal life may in critical time windows programme tissue development leading to organ dysfunction with potentially harmful consequences in adulthood such as diabetes. In rats, the beta cell mass of progeny from dams fed with a low-protein (LP) diet during gestation is decreased at birth and metabolic perturbation lasts through adulthood even though a normal diet is given after birth or after weaning. Maternal and fetal plasma taurine levels are suboptimal. Maternal taurine supplementation prevents these induced abnormalities. In this study, we aimed to reveal changes in gene expression in fetal islets affected by the LP diet and how taurine may prevent these changes.

Abstract: — Our study was designed to determine the calcium and oxygen paradoxes in isolated rat hepatocytes, and to evaluate the cytoprotective effects of taurine on hepatocytes during oxygenation, hypoxia, and on these paradoxes. The calcium and oxygen paradoxes were clearly revealed in isolated rat hepatocytes. As the formation of the superoxide radical was accelerated by the hyperbaric conditions and the calcium ions, drugs such as superoxide dismutase and a calcium channel blocking agent (verapamil), prevented these paradoxes. Taurine decreased the oxygenation-induced lipid peroxidation of hepatocytes, and prevented the hypoxia-induced hepatocyte death in a calcium-containing medium, but not in a calcium-free medium. Taurine also protected the hepatocytes from injuries associated with the calcium and oxygen paradoxes due to the inhibition of sudden calcium influx into the hepatocytes.