Taurine Abstracts 6


Taurine ameliorates neuropathy via regulating NF-κB and Nrf2/HO-1 signaling cascades in diabetic rats.
(Agca et al., 2014) Download
Diabetic neuropathy is one of common complications of diabetes mellitus. Hyperglycemia induced oxidative stress involves in the development of diabetic neuropathy, which could be reversed by supplementation of taurine, an endogenous antioxidant. This experiment was conducted to evaluate alterations in the expressions of transcription factors [nuclear factor kappa B (NF-κB), nuclear factor-E2-related factor-2 (Nrf2), and heme oxygenase 1 (HO-1)] and glucose transporters and glucose metabolism in the brain of diabetic rats. In a 2×2 factorially arranged groups, taurine (2%) or water was administered per orally to healthy and streptozotocin (STZ)-induced diabetic rats (n=10 per group) for 8 weeks. Diabetes was associated with weight loss, hyperglycemia, and oxidative stress as reflected by increased serum malondialdehyde (MDA) concentrations. Diabetic rat brains had increased the NF-κB expression and decreased the Nrf2, HO-1, GLUT1,3 expressions as compared to healthy rat brains. Supplemental taurine did not alter body weight and blood glucose concentration, but partially reduced serum MDA concentration in the diabetic rats. Taurine also partially alleviated neuroinflammation as reflected by suppressed the NF-κB expression and enhanced the Nrf2, HO-1, GLUT1,3 expressions in the diabetic rats. In conclusion, taurine reduces the severity of oxidative stress through activating antioxidative defense signaling pathway in diabetic rat brain.

Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and reproductive organ damage in Wistar rats: A biochemical and histological study.
            (Al-Asmari et al., 2016) Download
5-Fluorouracil is one of the most commonly used anticancer drugs for the treatment of various types of cancer but has potential adverse effects such as intestinal mucositis, renal, hepatic, and reproductive organ toxicity. Attention has been given to approaches to reduce the side effects and improve the therapeutic effectiveness of chemotherapeutic drugs. In this study, we have investigated the protective effect of taurine (Tau) on 5-fluorouracil (5-FU) induced adverse effects in Wistar rats. Animals were divided into four groups with six animals (n = 6) in each group. Group I received vehicle only and served as control group. Groups II, III, and IV animals were given oral gavage of 5-FU at 50 mg/kg body weight for 4 days. Tau was given to the animals of groups III and IV 30 min prior to 5-FU administration. We observed marked elevation in the myeloperoxidase (MPO) activity after 5-FU administration, which was reversed by Tau pretreatment. Histological observation of liver, kidney, intestine, testis, and prostate revealed that 5-FU administration resulted in anomalies like distortion of normal cellular architecture, infiltration of inflammatory cells, and loss of cellular integrity. These histopathological changes were markedly suppressed by Tau treatment. In conclusion, biochemical and histological findings of this study suggest that Tau has strong preventive potential against complications of anticancer drug 5-FU and hence Tau may play an important role in combinational chemotherapy to enhance the therapeutic efficacy of anticancer drugs.

Attenuation of rotenone toxicity in SY5Y cells by taurine and N-acetyl cysteine alone or in combination.
            (Alkholifi and Albers, 2015) Download
There is accumulating evidence that supports the involvement of reactive oxygen species (ROS), mitochondrial dysfunction and inflammation in the pathogenesis of neurodegenerative diseases. Thus, it is plausible that a multi-targeted therapeutic approach may be a more effective strategy to retard or even potentially halt the progression of the disease. Taurine is an organic acid that has a role in the regulation of oxidative stress and promoting mitochondrial normal functions, and N-Acetyl cysteine (NAC) is a well-known anti-oxidant and glutathione precursor. The main purpose of this study was to examine the cytoprotective effects of taurine alone or in combination with NAC against rotenone-induced toxicity in the SH-SY5Y neuroblastoma cell line. Taurine treatment produced a concentration-dependent reduction in rotenone-induced cell death. From this, we tested sub-effective concentrations of taurine in combination with low, sub-effective concentrations of NAC against rotenone toxicity, and found the combined treatment afforded greater cytoprotection than either treatment alone. The combined taurine/NAC treatment also attenuated rotenone-induced reductions in aconitase activity suggesting the cytoprotection afforded by the combined treatment may be associated with anti-oxidative mechanisms. Together, our data suggest that a multi-targeted approach may yield new avenues of research exploring the utility of combining therapeutic agents with different mechanisms of actions at concentrations lower than previously tested and shown to be cytoprotective.

A possible central mechanism in autism spectrum disorders, part 1.
            (Blaylock, 2008) Download
The autism spectrum disorders (ASD) are a group of related neurodevelopmental disorders that have been increasing in incidence since the 1980s. Despite a considerable amount of data being collected from cases, a central mechanism has not been offered. A careful review of ASD cases discloses a number of events that adhere to an immunoexcitotoxic mechanism. This mechanism explains the link between excessive vaccination, use of aluminum and ethylmercury as vaccine adjuvants, food allergies, gut dysbiosis, and abnormal formation of the developing brain. It has now been shown that chronic microglial activation is present in autistic brains from age 5 years to age 44 years. A considerable amount of evidence, both experimental and clinical, indicates that repeated microglial activation can initiate priming of the microglia and that subsequent stimulation can produce an exaggerated microglial response that can be prolonged. It is also known that one phenotypic form of microglia activation can result in an outpouring of neurotoxic levels of the excitotoxins, glutamate and quinolinic acid. Studies have shown that careful control of brain glutamate levels is essential to brain pathway development and that excesses can result in arrest of neural migration, as well as dendritic and synaptic loss. It has also been shown that certain cytokines, such as TNF-alpha, can, via its receptor, interact with glutamate receptors to enhance the neurotoxic reaction. To describe this interaction I have coined the term immunoexcitotoxicity, which is described in this article.

A possible central mechanism in autism spectrum disorders, part 2: immunoexcitotoxicity.
            (Blaylock, 2009a) Download
In this section, I explore the effects of mercury and inflammation on transsulfuration reactions, which can lead to elevations in androgens, and how this might relate to the male preponderance of autism spectrum disorders (ASD). It is known that mercury interferes with these biochemical reactions and that chronically elevated androgen levels also enhance the neurodevelopmental effects of excitotoxins. Both androgens and glutamate alter neuronal and glial calcium oscillations, which are known to regulate cell migration, maturation, and final brain cytoarchitectural structure. Studies have also shown high levels of DHEA and low levels of DHEA-S in ASD, which can result from both mercury toxicity and chronic inflammation. Chronic microglial activation appears to be a hallmark of ASD. Peripheral immune stimulation, mercury, and elevated levels of androgens can all stimulate microglial activation. Linked to both transsulfuration problems and chronic mercury toxicity are elevations in homocysteine levels in ASD patients. Homocysteine and especially its metabolic products are powerful excitotoxins. Intimately linked to elevations in DHEA, excitotoxicity and mercury toxicity are abnormalities in mitochondrial function. A number of studies have shown that reduced energy production by mitochondria greatly enhances excitotoxicity. Finally, I discuss the effects of chronic inflammation and elevated mercury levels on glutathione and metallothionein.


A possible central mechanism in autism spectrum disorders, part 3: the role of excitotoxin food additives and the synergistic effects of other environmental toxins.
            (Blaylock, 2009b) Download
There is compelling evidence from a multitude of studies of various design indicating that foodborne excitotoxin additives can elevate blood and brain glutamate to levels known to cause neurodegeneration and in the developing brain, abnormal connectivity. Excitotoxins are also secreted by microglial activation when they are in an activated state. Recent studies, discussed in part 1 of this article, indicate that chronic microglial activation is common in the autistic brain. The interaction between excitotoxins, free radicals, lipid peroxidation products, inflammatory cytokines, and disruption of neuronal calcium homeostasis can result in brain changes suggestive of the pathological findings in cases of autism spectrum disorders. In addition, a number of environmental neurotoxins, such as fluoride, lead, cadmium, and aluminum, can result in these pathological and biochemical changes.

Natural plant products and extracts that reduce immunoexcitotoxicity-associated neurodegeneration and promote repair within the central nervous system.
            (Blaylock and Maroon, 2012) Download
Our understanding of the pathophysiological and biochemical basis of a number of neurological disorders has increased enormously over the last three decades. Parallel with this growth of knowledge has been a clearer understanding of the mechanism by which a number of naturally occurring plant extracts, as well as whole plants, can affect these mechanisms so as to offer protection against injury and promote healing of neurological tissues. Curcumin, quercetin, green tea catechins, balcalein, and luteolin have been extensively studied, and they demonstrate important effects on cell signaling that go far beyond their antioxidant effects. Of particular interest is the effect of these compounds on immunoexcitotoxicity, which, the authors suggest, is a common mechanism in a number of neurological disorders. By suppressing or affecting microglial activation states as well as the excitotoxic cascade and inflammatory mediators, these compounds dramatically affect the pathophysiology of central nervous system disorders and promote the release and generation of neurotrophic factors essential for central nervous system healing. We discuss the various aspects of these processes and suggest future directions for study.


Taurine supplementation modulates glucose homeostasis and islet function.
            (Carneiro et al., 2009) Download
Taurine is a conditionally essential amino acid for human that is involved in the control of glucose homeostasis; however, the mechanisms by which the amino acid affects blood glucose levels are unknown. Using an animal model, we have studied these mechanisms. Mice were supplemented with taurine for 30 d. Blood glucose homeostasis was assessed by intraperitoneal glucose tolerance tests (IPGTT). Islet cell function was determined by insulin secretion, cytosolic Ca2+ measurements and glucose metabolism from isolated islets. Islet cell gene expression and translocation was examined via immunohistochemistry and quantitative real-time polymerase chain reaction. Insulin signaling was studied by Western blot. Islets from taurine-supplemented mice had: (i) significantly higher insulin content, (ii) increased insulin secretion at stimulatory glucose concentrations, (iii) significantly displaced the dose-response curve for glucose-induced insulin release to the left, (iv) increased glucose metabolism at 5.6 and 11.1-mmol/L concentrations; (v) slowed cytosolic Ca2+ concentration ([Ca2+]i) oscillations in response to stimulatory glucose concentrations; (vi) increased insulin, sulfonylurea receptor-1, glucokinase, Glut-2, proconvertase and pancreas duodenum homeobox-1 (PDX-1) gene expression and (vii) increased PDX-1 expression in the nucleus. Moreover, taurine supplementation significantly increased both basal and insulin stimulated tyrosine phosphorylation of the insulin receptor in skeletal muscle and liver tissues. Finally, taurine supplemented mice showed an improved IPGTT. These results indicate that taurine controls glucose homeostasis by regulating the expression of genes required for glucose-stimulated insulin secretion. In addition, taurine enhances peripheral insulin sensitivity.

CSF excitatory amino acids and severity of illness in Alzheimer's disease.
            (Csernansky et al., 1996) Download
Researchers have proposed that increased release of excitatory amino acids (EAAs) is involved in the pathogenesis of dementia of the Alzheimer type (DAT), and CSF EAA concentrations have been measured to obtain evidence in support of this hypothesis. However, previous comparisons of CSF EAA concentrations in patients with DAT and in controls have yielded inconsistent results, perhaps because patient samples have been heterogeneous as to dementia severity. To determine whether there are changes in CSF concentrations of EAAs related to severity of illness in patients with DAT, we measured CSF concentrations of glutamate, aspartate, and taurine in 32 subjects with DAT, in whom we also assessed the severity of illness using clinical and neuropsychological measures, and 11 age-matched controls. The results suggested that increased CSF aspartate and glutamate concentrations, as well as decreased taurine concentrations, may occur in some persons with more advanced symptoms of DAT.


Role of taurine uptake on the induction of long-term synaptic potentiation.
            (del Olmo et al., 2004) Download
Taurine application in the CA1 area of rat hippocampal slices induces a long-lasting potentiation of excitatory synaptic transmission that has some mechanistic similitude with the late phase of long-term potentiation (L-LTP). Previous indirect evidence such as temperature and sodium dependence indicated that taurine uptake is one of the primary steps leading to the taurine-induced synaptic potentiation. We show that taurine-induced potentiation is not related to the intracellular accumulation of taurine and is not impaired by 2-guanidinoethanesulphonic acid, a taurine transport inhibitor that is a substrate of taurine transporter. We have found that taurine uptake in hippocampal synaptosomes was inhibited by SKF 89976A, a GABA uptake blocker that is not transportable by GABA transporters. SKF 89976A prevents the induction of synaptic potentiation by taurine application. This effect is neither mimicked by nipecotic acid, a broad inhibitor of GABA transporters that does not affect taurine uptake, nor by NO-711, a specific and potent inhibitor of GABA transporter GAT-1. In addition, L-LTP induced by trains of high-frequency stimulation is also inhibited by SKF 89976A, and taurine, at a concentration that does not change basal synaptic transmission, overcomes such inhibition. We conclude that taurine induces synaptic potentiation through the activation of a system transporting taurine and that taurine uptake is required for the induction of synaptic plasticity phenomena such as L-LTP.

Elimination of cardiac arrhythmias using oral taurine with l-arginine with case histories: Hypothesis for nitric oxide stabilization of the sinus node.
            (Eby and Halcomb, 2006) Download
We searched for nutrient deficiencies that could cause cardiac arrhythmias [premature atrial contractions (PACs), premature ventricular contractions (PVCs), atrial fibrillation, and related sinus pauses], and found literature support for deficiencies of taurine and l-arginine. Case histories of people with very frequent arrhythmias are presented showing 10-20g taurine per day reduced PACs by 50% and prevented all PVCs but did not prevent pauses. Adding 4-6g of l-arginine immediately terminated essentially all remaining pauses and PACs, maintaining normal cardiac rhythm with continued treatment. Effects of taurine useful in preventing arrhythmias include regulating potassium, calcium and sodium levels in the blood and tissues, regulating excitability of the myocardium, and protecting against free radicals damage. Taurine restored energy and endurance in one of the cases from a debilitated status to normal. Arrhythmias may also respond to taurine because it dampens activity of the sympathetic nervous system and dampens epinephrine release. l-arginine may have anti-arrhythmic properties resulting from its role as a nitric oxide (NO) precursor and from its ability to restore sinus rhythm spontaneously. Endogenous production of taurine and l-arginine may decline in aging perturbing cardiac rhythm, and these "conditional" essential nutrients therefore become "essential" and require supplementation to prevent morbidity and mortality. l-arginine is hypothesized to prevent cardiac arrhythmias by NO stabilization of the sinus node. Cardiac arrhythmias having no known cause in otherwise healthy people are hypothesized to be symptoms of deficiencies of taurine and arginine.

Taurine: the comeback of a neutraceutical in the prevention of retinal degenerations.
            (Froger et al., 2014) Download
Taurine is the most abundant amino acid in the retina. In the 1970s, it was thought to be involved in retinal diseases with photoreceptor degeneration, because cats on a taurine-free diet presented photoreceptor loss. However, with the exception of its introduction into baby milk and parenteral nutrition, taurine has not yet been incorporated into any commercial treatment with the aim of slowing photoreceptor degeneration. Our recent discovery that taurine depletion is involved in the retinal toxicity of the antiepileptic drug vigabatrin has returned taurine to the limelight in the field of neuroprotection. However, although the retinal toxicity of vigabatrin principally involves a deleterious effect on photoreceptors, retinal ganglion cells (RGCs) are also affected. These findings led us to investigate the possible role of taurine depletion in retinal diseases with RGC degeneration, such as glaucoma and diabetic retinopathy. The major antioxidant properties of taurine may influence disease processes. In addition, the efficacy of taurine is dependent on its uptake into retinal cells, microvascular endothelial cells and the retinal pigment epithelium. Disturbances of retinal vascular perfusion in these retinal diseases may therefore affect the retinal uptake of taurine, resulting in local depletion. The low plasma taurine concentrations observed in diabetic patients may further enhance such local decreases in taurine concentration. We here review the evidence for a role of taurine in retinal ganglion cell survival and studies suggesting that this compound may be involved in the pathophysiology of glaucoma or diabetic retinopathy. Along with other antioxidant molecules, taurine should therefore be seriously reconsidered as a potential treatment for such retinal diseases.

Functional expression and subcellular localization of the taurine transporter TauT in murine neural precursors.
            (Hernández-Benítez et al., 2010) Download
Taurine addition to cultured embryonic neural precursor cells (NPC) significantly increased cell proliferation [Hernández-Benítez et al., 2010]. The medium used for NPC growing and proliferation is a fetal serum-free medium, and therefore, NPC become taurine depleted. Addition of taurine to the cultured medium fully replenished the cell taurine pool, suggesting the functional expression of a taurine transporter (TauT) in these cells. In the present study, TauT in NPC was functionally characterized and its protein expression and the subcellular distribution of immunoreactivity were determined. ³H-taurine uptake in NPC could be separated into a non-saturable component and a Na(+)/Cl⁻-dependent, saturable component. The saturable component showed an apparent 2:1:1 Na(+)/Cl⁻/taurine stoichiometry, a V(max) of 0.39 ± 0.04 nmol/mg protein/min, and a K(m) of 21.7 ± 2.6 μM. TauT in NPC was strongly inhibited by hypotaurine and β-alanine (92 and 79%, respectively) and reduced (71%) by γ-aminobutyric acid. TauT protein is expressed in NPC as a single band of about 70 kDa. Essentially all (98.8%) of the neurosphere-forming cells were positive to TauT immunoreactivity. Immunolocalization visualized by confocal microscopy localized TauT predominantly at the cell membrane. TauT was also found at the cytosol and only occasionally at the nuclear membrane. This study represents the first characterization of TauT in NPC.

Taurine attenuates chemotherapy-induced nausea and vomiting in acute lymphoblastic leukemia.
            (Islambulchilar et al., 2015) Download
Taurine has multiple physiological activities and it is decreased by chemotherapy. The purpose of our study was to evaluate the effect of oral taurine supplementation on the incidence of chemotherapy-induced nausea and vomiting in patients with acute lymphoblastic leukemia. Forty young patients aged over 16 (range: 16-23 years) suffering from acute lymphoblastic leukemia (all receiving same chemotherapy regimen) were recruited for the study at the beginning of maintenance course of their chemotherapy. The study population was randomized in a double-blind manner to receive either taurine or placebo (2 g per day orally, divided into two doses, taken 6 h after chemotherapeutic agents) for 6 months. Life quality and adverse effects including nausea and vomiting, taste and smell alterations, and weariness were assessed using a questionnaire. Data were analyzed using Pearson's Chi-square test. Of 40 participants, 32 finished the study (14 female and 18 male; mean age 19.2 ± 1.9 years). Four treatment and four placebo arm patients discontinued: one immigrated from the province, one died during the study, and six refused to continue. The results indicated that taurine-supplemented patients reported a significant (P < 0.05) improvement in chemotherapy-induced nausea and/or vomiting after taking taurine during study. Taurine significantly improved chemotherapy-induced taste and smell alterations (P < 0.05). Moreover, taurine significantly reduced weariness compared to placebo group (P < 0.05). This study showed that taurine co-administration decreased chemotherapy-induced nausea and vomiting during the maintenance therapy in acute lymphoblastic leukemia.


Taurine ameliorates neurobehavioral, neurochemical and immunohistochemical changes in sporadic dementia of Alzheimer's type (SDAT) caused by intracerebroventricular streptozotocin in rats.
            (Javed et al., 2013) Download
Oxidative loads in the brain are involved in age related impairments like learning and memory as well as neurodegeneration. Taurine, the most abundant free amino acid in humans has many potential health benefits through its anti-oxidant and anti-inflammatory properties. Therefore, we investigated the neuroprotective potential of taurine on oxidative stress, neuronal loss and memory impairments in streptozotocin model of cognitive impairments in rats. The cognitive impairment was developed by giving single intracerebroventricular (ICV) injection of streptozotocin (STZ) 3 mg/kg body weight bilaterally. An increased latency and path length was observed in ICV-STZ group animals as compared to sham group animals and these were inhibited significantly in STZ group pre-treated with taurine (50 mg/kg body weight orally once daily for 15 days). Moreover, the significantly depleted content of GSH and elevated level of thiobarbituric acid reactive substances (TBARS) in ICV-STZ group animals were protected significantly with pre-treatment of taurine. The activity of antioxidant enzymes, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, catalase, and superoxide dismutase was decreased in STZ group as compared to sham group and pre-treatment of STZ group with taurine has protected their activities significantly. Furthermore, the increased activity of acetylcholine esterase and decreased expression of choline acetyl transferase were attenuated by the pre-treatment of taurine. Taurine also protected the morphology of the hippocampal pyramidal neurons. This study concludes that the prophylactic intervention of taurine may be used to prevent the deterioration of cognitive functions and neurobehavioral activities, often associated with the generation of free radicals.



Agca, CA, et al. (2014), ‘Taurine ameliorates neuropathy via regulating NF-κB and Nrf2/HO-1 signaling cascades in diabetic rats.’, Food Chem Toxicol, 71 116-21. PubMed: 24907624
Al-Asmari, AK, et al. (2016), ‘Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and reproductive organ damage in Wistar rats: A biochemical and histological study.’, Hum Exp Toxicol, 35 (1), 10-20. PubMed: 25724421
Alkholifi, FK and DS Albers (2015), ‘Attenuation of rotenone toxicity in SY5Y cells by taurine and N-acetyl cysteine alone or in combination.’, Brain Res, 1622 409-13. PubMed: 26168893
Blaylock, RL (2008), ‘A possible central mechanism in autism spectrum disorders, part 1.’, Altern Ther Health Med, 14 (6), 46-53. PubMed: 19043938
——— (2009a), ‘A possible central mechanism in autism spectrum disorders, part 2: immunoexcitotoxicity.’, Altern Ther Health Med, 15 (1), 60-67. PubMed: 19161050
——— (2009b), ‘A possible central mechanism in autism spectrum disorders, part 3: the role of excitotoxin food additives and the synergistic effects of other environmental toxins.’, Altern Ther Health Med, 15 (2), 56-60. PubMed: 19284184
Blaylock, RL and J Maroon (2012), ‘Natural plant products and extracts that reduce immunoexcitotoxicity-associated neurodegeneration and promote repair within the central nervous system.’, Surg Neurol Int, 3 19. PubMed: 22439110
Carneiro, EM, et al. (2009), ‘Taurine supplementation modulates glucose homeostasis and islet function.’, J Nutr Biochem, 20 (7), 503-11. PubMed: 18708284
Csernansky, JG, et al. (1996), ‘CSF excitatory amino acids and severity of illness in Alzheimer’s disease.’, Neurology, 46 (6), 1715-20. PubMed: 8649576
del Olmo, N, et al. (2004), ‘Role of taurine uptake on the induction of long-term synaptic potentiation.’, Eur J Neurosci, 19 (7), 1875-86. PubMed: 15078561
Eby, G and WW Halcomb (2006), ‘Elimination of cardiac arrhythmias using oral taurine with l-arginine with case histories: Hypothesis for nitric oxide stabilization of the sinus node.’, Med Hypotheses, 67 (5), 1200-4. PubMed: 16797868
Froger, N, et al. (2014), ‘Taurine: the comeback of a neutraceutical in the prevention of retinal degenerations.’, Prog Retin Eye Res, 41 44-63. PubMed: 24721186
Hernández-Benítez, R, et al. (2010), ‘Functional expression and subcellular localization of the taurine transporter TauT in murine neural precursors.’, Dev Neurosci, 32 (4), 321-28. PubMed: 21160187
Islambulchilar, M, et al. (2015), ‘Taurine attenuates chemotherapy-induced nausea and vomiting in acute lymphoblastic leukemia.’, Amino Acids, 47 (1), 101-9. PubMed: 25323734
Javed, H, et al. (2013), ‘Taurine ameliorates neurobehavioral, neurochemical and immunohistochemical changes in sporadic dementia of Alzheimer’s type (SDAT) caused by intracerebroventricular streptozotocin in rats.’, Neurol Sci, 34 (12), 2181-92. PubMed: 23681104