High Levels Of Taurine Research Articles

Nutritional composition of sea squirts from Iwate Prefecture, Japan

n this study, due to the effects of the Great East Japan Earthquake in 2011, sea squirts were not exported overseas and were discarded without being used for food. We addressed the disposal issue by raising awareness of sea squirts and incorporating them into food. When the general food composition of peeled sea squirts from Iwate Prefecture was analyzed, it was confirmed that they had a high ash content of 5.9% protein, 0.3% fat, 6.3% carbohydrates, and 2.9% ash, similar to shellfish. The mineral content of sea squirts from Iwate Prefecture revealed high levels of magnesium, iron, and zinc, similar to those of shellfish. The analysis of free amino acids in sea squirts revealed high levels of taurine, glutamic acid, proline, and alanine, indicating high amino acid content related to the taste of sea squirts, particularly sweetness and umami. It was confirmed that sea squirts are rich in minerals and amino acids, making them functional foods beneficial to human health.

Exploring the aging process of cognitively healthy adults by analyzing cerebrospinal fluid metabolomics using liquid chromatography-tandem mass spectrometry

BackgroundDuring biological aging, significant metabolic dysregulation in the central nervous system may lead to cognitive decline and neurodegeneration. However, the metabolomics of the aging process in cerebrospinal fluid (CSF) has not been thoroughly explored.MethodsIn this cohort study of CSF metabolomics using liquid chromatography-mass spectrometry (LC–MS), fasting CSF samples collected from 92 cognitively unimpaired adults aged 20–87 years without obesity or diabetes were analyzed.ResultsWe identified 37 metabolites in these CSF samples with significant positive correlations with aging, including cysteine, pantothenic acid, 5-hydroxyindoleacetic acid (5-HIAA), aspartic acid, and glutamate; and two metabolites with negative correlations, asparagine and glycerophosphocholine. The combined alterations of asparagine, cysteine, glycerophosphocholine, pantothenic acid, sucrose, and 5-HIAA showed a superior correlation with aging (AUC = 0.982). These age-correlated changes in CSF metabolites might reflect blood–brain barrier breakdown, neuroinflammation, and mitochondrial dysfunction in the aging brain. We also found sex differences in CSF metabolites with higher levels of taurine and 5-HIAA in women using propensity-matched comparison.ConclusionsOur LC–MS metabolomics of the aging process in a Taiwanese population revealed several significantly altered CSF metabolites during aging and between the sexes. These metabolic alterations in CSF might provide clues for healthy brain aging and deserve further exploration.

Taurine depletion impairs cardiac function and affects tolerance to hypoxia and high temperatures in brook char (Salvelinus fontinalis).

Physiological and environmental stressors can cause osmotic stress in fish hearts, leading to a reduction in intracellular taurine concentration. Taurine is a β-amino acid known to regulate cardiac function in other animal models but its role in fish has not been well characterized. We generated a model of cardiac taurine deficiency (TD) by feeding brook char (Salvelinus fontinalis) a diet enriched in β-alanine, which inhibits cardiomyocyte taurine uptake. Cardiac taurine levels were reduced by 21% and stress-induced changes in normal taurine handling were observed in TD brook char. Responses to exhaustive exercise and acute thermal and hypoxia tolerance were then assessed using a combination of in vivo, in vitro and biochemical approaches. Critical thermal maximum was higher in TD brook char despite significant reductions in maximum heart rate. In vivo, TD brook char exhibited a lower resting heart rate, blunted hypoxic bradycardia and a severe reduction in time to loss of equilibrium under hypoxia. In vitro function was similar between control and TD hearts under oxygenated conditions, but stroke volume and cardiac output were severely compromised in TD hearts under severe hypoxia. Aspects of mitochondrial structure and function were also impacted in TD permeabilized cardiomyocytes, but overall effects were modest. High levels of intracellular taurine are required to achieve maximum cardiac function in brook char and cardiac taurine efflux may be necessary to support heart function under stress. Taurine appears to play a vital, previously unrecognized role in supporting cardiovascular function and stress tolerance in fish.

Effects of dietary oat supplementation on carcass traits, muscle metabolites, amino acid profiles, and its association with meat quality of Small-tail Han sheep

Oat supplementation of the ruminant diet can improve growth performance and meat quality traits, but the role of muscle metabolites has not been evaluated. This study aimed to establish whether oat grass supplementation (OS) of Small-tail Han sheep improved growth performance and muscle tissue metabolites that are associated with better meat quality and flavor. After 90-day, OS fed sheep had higher live-weight and carcass-weight, and lower carcass fat. Muscle metabolomics analysis showed that OS fed sheep had higher levels of taurine, l-carnitine, inosine-5′-monophospgate, cholic acid, and taurocholic acid, which are primarily involved in taurine and hypotaurine metabolism, purine metabolism, and bile acid biosynthesis and secretion, decreased fat accumulation and they promote functional or flavor metabolites. OS also increased muscle levels of amino acids that are attributed to better quality and flavorsome mutton. These findings provided further evidence for supplementing sheep with oat grass to improve growth performance and meat quality.

A multi-omics based anti-inflammatory immune signature characterizes long COVID-19 syndrome

To investigate long COVID-19 syndrome (LCS) pathophysiology, we performed an exploratory study with blood plasma derived from three groups: 1) healthy vaccinated individuals without SARS-CoV-2 exposure; 2) asymptomatic recovered patients at least three months after SARS-CoV-2 infection and; 3) symptomatic patients at least 3months after SARS-CoV-2 infection with chronic fatigue syndrome or similar symptoms, here designated as patients with long COVID-19 syndrome (LCS). Multiplex cytokine profiling indicated slightly elevated pro-inflammatory cytokine levels in recovered individuals in contrast to patients with LCS. Plasma proteomics demonstrated low levels of acute phase proteins and macrophage-derived secreted proteins in LCS. High levels of anti-inflammatory oxylipins including omega-3 fatty acids in LCS were detected by eicosadomics, whereas targeted metabolic profiling indicated high levels of anti-inflammatory osmolytes taurine and hypaphorine, but low amino acid and triglyceride levels and deregulated acylcarnitines. A model considering alternatively polarized macrophages as a major contributor to these molecular alterations is presented.

Taurine metabolism is modulated in Vibrio-infected Penaeus vannamei to shape shrimp antibacterial response and survival

BackgroundNumerous microorganisms are found in aquaculture ponds, including several pathogenic bacteria. Infection of cultured animals by these pathogens results in diseases and metabolic dysregulation. However, changes in the metabolic profiles that occur at different infection stages in the same ponds and how these metabolic changes can be modulated by exogenous metabolites in Penaeus vannamei remain unknown.ResultsHere, we collected gastrointestinal tract (GIT) samples from healthy, diseased, and moribund P. vannamei in the same aquaculture pond for histological, metabolic, and transcriptome profiling. We found that diseased and moribund shrimp with empty GITs and atrophied hepatopancreas were mainly infected with Vibrio parahaemolyticus and Vibrio harveyi. Although significant dysregulation of crucial metabolites and their enzymes were observed in diseased and moribund shrimps, diseased shrimp expressed high levels of taurine and taurine metabolism-related enzymes, while moribund shrimp expressed high levels of hypoxanthine and related metabolism enzymes. Moreover, a strong negative correlation was observed between taurine levels and the relative abundance of V. parahaemolyticus and V. harveyi. Besides, exogenous taurine enhanced shrimp survival against V. parahaemolyticus challenge by increasing the expression of key taurine metabolism enzymes, mainly, cysteine dioxygenase (CDO) and cysteine sulfinic acid decarboxylase (CSD).ConclusionsOur study revealed that taurine metabolism could be modulated by exogenous supplementation to improve crustacean immune response against pathogenic microbes.5E3vY5nuGW9ktCAisXY2AkVideo

Taurine enhances the antitumor efficacy of PD-1 antibody by boosting CD8+ T cell function.

The functional state of CD8+ T cells determines the therapeutic efficacy of PD-1 blockade antibodies in tumors. Amino acids are key nutrients for maintaining T cell antitumor immunity. In this study, we used samples from lung cancer patients treated with PD-1 blockade antibodies to assay the amino acids in their serum by mass spectrometry. We found that lung cancer patients with high serum taurine levels generally responded to PD-1 blockade antibody therapy, in parallel with the secretion of high levels of cytotoxic cytokines (IFN-γ and TNF-α). CD8+ T cells cultured with exogenous taurine exhibited decreased apoptosis, enhanced proliferation, and increased secretion of cytotoxic cytokines. High SLC6A6 expression in CD8+ T cells was positively associated with an effector T cell signature. SLC6A6 knockdown limited the function and proliferation of CD8+ T cells. RNA sequencing revealed that SLC6A6 knockdown altered the calcium signaling pathway, oxidative phosphorylation, and T cell receptor signaling in CD8+ T cells. Furthermore, taurine enhanced T cell proliferation and function in vitro by stimulation of PLCγ1-mediated calcium and MAPK signaling. Taurine plus immune checkpoint blockade antibody significantly attenuated tumor growth and markedly improved the function and proliferation of CD8+ T cells in a mouse tumor model. Thus, our findings indicate that taurine is an important driver for improving CD8+ T cell immune responses and could serve as a potential therapeutic agent for cancer patients.

Versatile Triad Alliance: Bile Acid, Taurine and Microbiota.

Taurine is the most abundant free amino acid in the body, and is mainly derived from the diet, but can also be produced endogenously from cysteine. It plays multiple essential roles in the body, including development, energy production, osmoregulation, prevention of oxidative stress, and inflammation. Taurine is also crucial as a molecule used to conjugate bile acids (BAs). In the gastrointestinal tract, BAs deconjugation by enteric bacteria results in high levels of unconjugated BAs and free taurine. Depending on conjugation status and other bacterial modifications, BAs constitute a pool of related but highly diverse molecules, each with different properties concerning solubility and toxicity, capacity to activate or inhibit receptors of BAs, and direct and indirect impact on microbiota and the host, whereas free taurine has a largely protective impact on the host, serves as a source of energy for microbiota, regulates bacterial colonization and defends from pathogens. Several remarkable examples of the interaction between taurine and gut microbiota have recently been described. This review will introduce the necessary background information and lay out the latest discoveries in the interaction of the co-reliant triad of BAs, taurine, and microbiota.

Increased Relative Abundance of Ruminoccocus Is Associated With Reduced Cardiovascular Risk in an Obese Population.

BackgroundObesity is a complex disease with underlying genetic, environmental, psychological, physiological, medical, and epigenetic factors. Obesity can cause various disorders, including cardiovascular diseases (CVDs), that are among the most prevalent chronic conditions in Qatar. Recent studies have highlighted the significant roles of the gut microbiome in improving the pathology of various diseases, including obesity. Thus, in this study, we aimed to investigate the effects of dietary intake and gut microbial composition in modulating the risk of CVD development in obese Qatari adults.MethodsWe enrolled 46 adult subjects (18–65 years of age) who were classified based on their CVD risk scores, calculated using the Framingham formula, into a CVD no-risk group (score of <10%, n = 36) and CVD risk group (score of ≥10%, n = 10). For each study subject, we measured the gut microbial composition with a 16s rDNA sequencing method that targeted the v3-v4 region using Illumina Miseq, and their nutritional status was recorded based on 24-h dietary recall. Dietary intake, bacterial taxa summary, diversity index, microbial markers, pathway analysis, and network correlation were determined for the study subjects.ResultsThe CVD risk group showed a lower intake of vitamin D, reduced relative abundance of genera Ruminococcus and Bifidobacterium, no change in bacterial diversity, and higher levels of taurine, hypotaurine, and lipoic acid metabolism than the CVD no-risk group. Besides, the relative abundance of genus Ruminococcus was positively correlated with the intake of protein, monounsaturated fat, vitamin A, and vitamin D.ConclusionTaken together, our results suggest that the genus Ruminococcus could be used as a microbial marker, and its reduced relative abundance could mediate the risk of CVDs in the Obese Qatari population.

Proximate Composition, Amino Acids, and Fatty Acids in the Adductor Muscle of the Giant Honeycomb Oyster Hyotissa hyotis (Linnaeus, 1758) from Jeju Island, Korea

The giant honeycomb oyster Hyotissa hyotis occurs at a high density in the shallow subtidal rocky bottom of Jeju Island off the south coast of Korea, where the sea surface temperature ranges from 14°C to 25°C seasonally. Unlike other oysters, H. hyotis has an extraordinarily large adductor muscle (AM) that accounts for more than 40% of the total tissue weight. This study analyzed the proximate composition, amino acids, and fatty acids of the AM of H. hyotis in Jeju Island to evaluate the nutritional potential. For the analyses, oysters were grouped based on their reproductive condition as prespawning (May–August), spawning (September–November), and postspawning (December–April). The AM contained a high level of protein (54.7%–69.4%) followed by carbohydrate (16.0%–25.3%) and lipid (4.5%–9.9%) throughout the year, indicating that the AM is enriched with protein. The total amino acids (TAA) in the AM ranged from 9.4 to 12.9 g/100 g dry weight annually, and essential amino acids accounted for up to 36.7% of the TAA. Like other marine bivalves, the AM contained a high level of taurine, which accounted for 26.5%–28.5% of the total free amino acids. The AM also included high levels of essential fatty acids, such as palmitic acid, docosahexaenoic acid, and eicosapentaenoic acid, as these fatty acids accounted for 35.9%–37.0% of the total fatty acids. The AM of prespawning oysters collected during May and August contained comparatively higher total proteins and carbohydrates. Results suggested that, like scallops and pen shells, the AM of the giant honeycomb oyster is highly suitable as seafood, and H. hyotis should be considered as a species of high potential for future aquaculture efforts.

Acute effects of energy drink consumption on left and right ventricular function - a 2-dimensional speckle tracking echocardiographic study.

Aim Energy drinks (ED) contain high levels of caffeine and taurine and are associated with several cardiovascular effects. We investigated acute effects of consuming low caffeine and taurine content ED on left ventricular (LV) and right ventricular (RV) function assessed by conventional and two-dimensional speckle tracking echocardiography.Material and methods In this crossover study, 34 healthy adults, age 19-48 yrs, drank an ED containing 53.25 milligrams of caffeine, 284 mg of taurine, or an equal volume of control drink (CD) on two separate sessions, 7-10 days apart. Standard echocardiographic and speckle tracking imaging were performed before and 60 min after consumption of the study beverages.Results Compared to CD, ED caused a significant increase in tricuspid annular plane systolic excursion (p=0.04) and RV systolic wave velocity (p=0.01) with no effect on global longitudinal strain when compared to CD. LV systolic function was not altered, but mitral early diastolic velocity by tissue Doppler imaging was significantly higher (p=0.031), and early diastolic strain rate, as measured by speckle tracking echocardiography, was significantly lower (p=0.022).Conclusion Reduced caffeine and taurine content ED does not affect LV systolic function, but increases RV longitudinal contractility and improves LV early diastolic filling.

Metabolic disturbances in systemic lupus erythematosus evaluated with UPLC-MS/MS.

Systemic lupus erythematosus (SLE) is an autoimmune disease. However, no surrogate biomarker is available for SLE diagnosis or predicting disease outcomes. Here, an ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS)-based metabolomics strategy was executed to conduct biomarker discovery in SLE. Metabolite profiles were analysed using UPLC-MS/MS analysis of serum samples obtained from the discovery cohort. Differentially expressed metabolites were identified using multivariate analyses. During the validation stage, the significant metabolites identified in the discovery cohort were quantified in a validation cohort using multiple reaction monitoring mass spectrometry (MRM-MS). Differences in serum metabolite levels and SLE disease activity markers were examined by using Spearman's correlation analysis. A total of 29 significant metabolites were identified by the UPLC-MS/MS analysis. These metabolites were primarily involved in fatty acid metabolism (20.69%) and phospholipid catabolism (17.24%). In the validation cohort, 11 of 29 metabolites were quantified, which demonstrated increased levels of pyroglutamic acid and L-phenylalanine in SLE patients compared with healthy controls. Patients with lupus nephritis (LN) presented with higher taurine levels, which could serve as a biomarker. The literature review indicated decreased levels of amino acids and adenosine among SLE patients and increased lipids, low-density lipoprotein, and very low-density lipoprotein among LN patients compared to healthy controls. Fatty acid metabolism and phospholipid catabolism were affected in SLE patients. Pyroglutamic acid and L-phenylalanine have the potential to act as SLE biomarkers, and taurine might be used to distinguish patients with and without LN.

Adverse Effects of Energy Drinks, a Challenge for Medicine: A Case Report.

In Mexico, an estimate of the monthly average consumption of these drinks was 36,240,000 liters [1]. The use of these products is to increase energy levels during physical activity or exam periods to avoid sleep. Despite the increase in its use, there is ignorance in its consumers about its level of safety in its consumption [2]. Energy drinks (ED) appeared on the market as a mixture of carbohydrates, vitamins, and caffeine. Later, alcohol blends were made for cocktails, so their popularity increased. The high consumption of ED is due to the mental stimulating effect by the high levels of caffeine, taurine and glucuronolactone [3].

Taurine Attenuates Catabolic Processes Related to the Onset of Sarcopenia

Sarcopenia that occurs with advancing age is characterized by a gradual loss of muscle protein component due to the activation of catabolic pathways, increased level of inflammation, and mitochondrial dysfunction. Experimental evidence demonstrates that several physio-pathological processes involved in the onset of sarcopenia may be counteracted by the intake of specific amino acids or antioxidant molecules, suggesting that diet may represent an effective strategy for improving the anabolic response of muscle during aging. The non-essential amino acid taurine is highly expressed in several mammalian tissues, including skeletal muscle where it is involved in the ion channel regulation, in the modulation of intracellular calcium concentration, and where it plays an important role as an antioxidant and anti-inflammatory factor. Here, with the purpose to reproduce the chronic low-grade inflammation characteristics of senescent muscle in an in vitro system, we exploited the role of Tumor Necrosis Factor α (TNF) and we analyzed the effect of taurine in the modulation of different signaling pathways known to be dysregulated in sarcopenia. We demonstrated that the administration of high levels of taurine in myogenic L6 cells stimulates the differentiation process by downregulating the expression of molecules involved in inflammatory pathways and modulating processes such as autophagy and apoptosis. Although further studies are currently ongoing in our laboratory to better elucidate the molecular mechanisms responsible for the positive effect of taurine on myogenic differentiation, this study suggests that taurine supplementation may represent a strategy to delay the loss of mass and functionality characteristic of senescent muscles.

Night Migratory Songbirds Exhibit Metabolic Ability to Support High Aerobic Capacity during Migration.

Aerobic metabolism in night migratory songbirds exhibit seasonal plasticity, which depends not only on annual life history stages (LHSs), viz., migratory/nonmigratory or breeding/nonbreeding, but also on the time of the day. Initially, we studied daily changes in behavior/physiology alongside aerobic metabolism intermediates using gas chromatography–mass spectrometry-based chemometric analyses of serum of migratory male redheaded buntings during low-energy wintering, that is, the nonmigrating LHS. Then, the metabolic phenotype of nonmigrating birds was compared with that of photostimulated migrating buntings, the latter representing the high-energy LHS. Diurnal changes such as daytime feeding and activity were reflected by increased fatty acid (FA, viz., palmitic, oleic, and linoleic acids) levels and protein catabolites, whereas higher night-time levels of short-chain FAs indicated lipolysis in night-fasted birds. High night-time levels of taurine, a sulfur amino acid, suggested the endogenous metabolite rendering an adaptive advantage to hyperglycaemic night migratory songbirds during the LHS with low daily energy expenditure. Conversely, migrating birds, largely night-active, exhibited higher circulatory FA, its mobilization, and increased aerobic catabolism, and the adipocyte-secreted lipid, palmitoylethanolamide (PEA), capable of activating the peroxisome proliferator-activated receptor α–PGCα axis, showed elevated levels throughout the day. PEA is known for anti-inflammatory and cannabinomimetic properties, and we show, for the first time, circadian changes in PEA levels in any migrating bird. Significantly higher levels of pyridoxal phosphate also suggested the bird’s protective ability to combat metabolic stress through high aerobic capacity during migration. This study elucidates putative “serum biomarkers” with a protective role in stress accrued by enhanced aerobic capacity requirements at the organismal level.

Taurine Promotes Neurite Outgrowth and Synapse Development of Both Vertebrate and Invertebrate Central Neurons

Taurine is a sulfur-containing amino acid that is widely expressed throughout the human brain, heart, retina, and muscle tissues. Taurine deficiency is associated with cardiomyopathy, renal dysfunction, abnormalities of the developing nervous system, and epilepsy which suggests a role specific to excitable tissues. Like vertebrates, invertebrates maintain high levels of taurine during embryonic and larval development, which decline during aging, indicating a potential developmental role. Notwithstanding its extensive presence throughout, taurine’s precise role/s during early brain development, function, and repair remains largely unknown in both vertebrate and invertebrate. Here, we investigated whether taurine affects neurite outgrowth, synapse formation, and synaptic transmission between postnatal day 0 rat cortical neurons in vitro, whereas its synaptogenic role was tested more directly using the Lymnaea soma-soma synapse model. We provide direct evidence that when applied at physiological concentrations, taurine exerts a significant neurotrophic effect on neuritic outgrowth and thickness of neurites as well as the expression of synaptic puncta as revealed by immunostaining of presynaptic synaptophysin and postsynaptic PSD95 proteins in rat cortical neurons, indicating direct involvement in synapse development. To demonstrate taurine’s direct effects on neurons in the absence of glia and other confounding factors, we next exploited individually identified pre- and postsynaptic neurons from the mollusk Lymnaea stagnalis. We found that taurine increased both the incidence of synapse formation (percent of cells that form synapses) and the efficacy of synaptic transmission between the paired neurons. This effect was comparable, but not additive, to Lymnaea trophic factor-induced synaptogenesis. This study thus provides direct morphological and functional evidence that taurine plays an important role in neurite outgrowth, synaptogenesis, and synaptic transmission during the early stages of brain development and that this role is conserved across both vertebrate and invertebrate species.

A Comparative Study of Rat Urine 1H-NMR Metabolome Changes Presumably Arising from Isoproterenol-Induced Heart Necrosis Versus Clarithromycin-Induced QT Interval Prolongation.

Cardiotoxicity remains a challenging concern both in drug development and in the management of various clinical situations. There are a lot of examples of drugs withdrawn from the market or stopped during clinical trials due to unpredicted cardiac adverse events. Obviously, current conventional methods for cardiotoxicity assessment suffer from a lack of predictivity and sensitivity. Therefore, there is a need for developing new tools to better identify and characterize any cardiotoxicity that can occur during the pre-clinical and clinical phases of drug development as well as after marketing in exposed patients. In this study, isoproterenol and clarithromycin were used as prototypical cardiotoxic agents in rats in order to evaluate potential biomarkers of heart toxicity at very early stages using 1H-NMR-based metabonomics. While isoproterenol is known to cause heart necrosis, clarithromycin may induce QT interval prolongation. Heart necrosis and QT prolongation were validated by histological analysis, serum measurement of lactate dehydrogenase/creatine phosphate kinase and QTc measurement by electrocardiogram (ECG). Urine samples were collected before and repeatedly during daily exposure to the drugs for 1H-NMR based-metabonomics investigations. Specific metabolic signatures, characteristic of each tested drug, were obtained from which potential predictive biomarkers for drug-induced heart necrosis and drug-induced QT prolongation were retrieved. Isoproterenol-induced heart necrosis was characterized by higher levels of taurine, creatine, glucose and by lower levels of Krebs cycle intermediates, creatinine, betaine/trimethylamine N-oxide (TMAO), dimethylamine (DMA)/sarcosine. Clarithromycin-induced QT prolongation was characterized by higher levels of creatinine, taurine, betaine/TMAO and DMA/sarcosine and by lower levels of Krebs cycle intermediates, glucose and hippurate.

Supplemental taurine during adolescence and early adulthood has sex-specific effects on cognition, behavior and neurotransmitter levels in C57BL/6J mice dependent on exposure window

The mammalian brain goes through final maturation during late adolescence and early adulthood with sex differences in timing. The key cellular processes, including changes in neurotransmitter receptor density and synaptic pruning, make this age uniquely vulnerable to neurotoxic insults. Teenagers and young adults are the major consumers of energy drinks, which contain high levels of taurine and caffeine. Taurine is one of the most abundant amino acids in the central nervous system, but the effects of supplemental taurine consumption during adolescence has not been well studied. We conducted an initial short-term exposure study with 0.12% taurine in drinking water and a long-term exposure dose-response study using 0.06 and 0.12% taurine in male and female C57BL/6J mice. We examined a broad range of cognitive functions and behaviors and measured neurotransmitter levels. We found no significant differences in anxiety, open field locomotor activity, or sensorimotor gating. However, we found impairments in novel object recognition and sex differences in Morris water maze. When taurine treatment stopped before behavioral experiments began, male mice had significant impairments in spatial learning and memory. In the dose-response study when taurine treatment continued throughout behavioral experiments, females had significant impairments. We also found sex differences in neurotransmitter levels with females having higher levels of glutamate, DOPAC and 5-HIAA. We conclude that both females and males are at risk from excess taurine consumption during final brain maturation.

Abstract 332: Novel Peptide Administered During CPR Improves Long-Term Survival After Prolonged Cardiac Arrest

Introduction: Cardiac arrest (CA) is a leading cause of death in the United State, affecting 600,000 people annually with overall survival rate of less than 10%. CPR and cooling are the few effective treatments that improve CA survival. No drugs are currently available to improve survival. Active cooling is more effective than targeted temperature management in improving survival, but can be difficult to implement clinically. We have developed a novel peptide (TAT-PHLPP) that inhibits PH domain and Leucine rich repeat Protein Phosphatases (PHLPP). When this peptide was administered intravenously (i.v.) during CPR, it expresses in both heart and brain within 5 min of intravenous injection and significantly improved 4 h survival in a 12 min mouse asystole arrest model. Hypothesis: We hypothesize that TAT-PHLPP improves neurologically intact long-term survival following SCA with improved early metabolic recovery. Methods: C57BL6 mice (n=20) were randomized to receive peptide treatment and appropriate blinding was ensured. A 12 min asystolic arrest was induced with KCl. CPR was started along with TAT-PHLPP (7.5 mg/kg) via i.v. Three day Survival was evaluated. Cerebral blood flow (CBF) and metabolic chemical exchange saturation transfer (CEST) contrast were measured with endogenous and dynamic arterial spin labeling (ASL) and CEST MRI respectively. Glucose utilization was assessed by pyruvate dehydrogenase (PDH) phosphorylation and ATP generation. Further, blood taurine and glutamate were measured. Results: Baseline characteristics including weight, temperature, heart rate, MAP were indistinguishable between the control (normal saline, NS) and peptide group. Compared to NS, TAT-PHLPP significantly improved 3-day survival with better neurological function. It progressively increased CBF and metabolic CEST contrast. It decreased p-PDH (increased activity) at 15 min post-ROSC and enhanced ATP generation in both heart and brain. It also reduced plasma taurine and glutamate concentrations as early as 5 min post-ROSC. Further, high levels of taurine and glutamate were detected in non-survivors. Conclusions: This novel therapy may have a high translational potential to reproduce critical outcomes of CPR cooling without physical cooling.

Effect of vitamin B12 and taurine on the alleviation of nutritional anaemia in common sole (Solea solea)

Sole fed commercial pellets develop a nutritional anaemia. This study assessed the impact of dietary B12 and taurine on the haematocrit (Hct) and haemoglobin (Hb) level and mineral absorption in anaemic sole. Anaemic sole was fed one of four diets. Diets were equal regarding mineral, amino acid and macronutrient composition and formulated, according to a two by two factorial design: two B12 (0.34 vs. 1.9 mg kg dm⁻¹) and two taurine levels (3.5 vs. 7.6 mg kg dm⁻¹). The feeding level was restricted and equal for all diets. Hct and Hb levels in anaemic sole are influenced by dietary B12. A “high” level of B12 increases the Hct and Hb level. An increasing level of taurine suppresses the stimulating effect of the “high” level of B12. The applied B12 and taurine levels were unable to completely alleviate the anaemia in sole. Nevertheless, sole needs high dietary levels of B12 to alleviate anaemia. The impact of B12 and taurine on Hb and Hct was not related to a change in the absorption of iron. A “high” level of B12 positively affected the absorption of chromium and a high level of taurine negatively affected the absorption of cobalt in sole.