Taurine inhibits M2 polarization of macrophages by promoting mitophagy / 细胞与分子免疫学杂志

Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.

Discovery of biomarkers related to abnormal lipid metabolism in liver and serum and intervention mechanism of ginsenoside Rb_1 in hyperlipidemia rats based on non-targeted metabolomics / 中国中药杂志

Through the non-targeted metabolomics study of endogenous substances in the liver and serum of hyperlipidemia rats, the biomarkers related to abnormal lipid metabolism in hyperlipidemia rats were found, and the target of ginsenoside Rb_1 in improving hyperlipidemia was explored and its mechanism was elucidated. The content of serum biochemical indexes of rats in each group was detected by the automatic biochemical analyzer. The metabolite profiles of liver tissues and serum of rats were analyzed by HPLC-MS. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to compare and analyze the metabolic data in the normal group, the hyperlipidemia group, and the ginsenoside Rb_1 group, and screen potential biomar-kers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that hyperlipemia induced dyslipidemia in rats, which was alleviated by ginsenoside Rb_1. The non-targeted metabolomics results showed that there were 297 differential metabolites in the liver tissues of hyperlipidemia rats, 294 differential metabolites in the serum samples, and 560 diffe-rential metabolites in the hyperlipidemia rats treated by ginsenoside Rb_1. Perillic acid and N-ornithyl-L-taurine were common metabolites in the liver and serum samples, which could be used as potential biomarkers for ginsenoside Rb_1 in the improvement of hyperlipidemia. As revealed by pathway enrichment in the liver and serum, ginsenoside Rb_1 could participate in the metabolic pathway of choline in both the liver and serum. In addition, ginsenoside Rb_1 also participated in the ABC transporter, alanine, aspartic acid, and glutamate metabolism, protein digestion and absorption, β-alanine metabolism, taurine and hypotaurine metabolism, caffeine metabolism, valine, leucine, and isoleucine biosynthesis, arachidonic acid metabolism, and methionine and cysteine metabolism to improve dyslipidemia in rats.

Effect of Anti-Oxidative of Ethyl Pyruvate and Taurine on the Red Blood Cell Storage at 4 ℃ / 中国实验血液学杂志

OBJECTIVE@#To investigate the anti-oxidative effect of ethyl pyruvate (EP) and taurine (TAU) on the quality of red blood cells stored at 4±2 ℃, hemolysis, energy metabolism and lipid peroxidation of the red blood cells in the preservation solution were studied at different intervals.@*METHODS@#At 4±2 ℃, the deleukocyte red blood cells were stored in the citrate-phosphate-dextrosesaline-adenine-1 (CPDA-1) preservation (control group), preservation solution with EP (EP-AS), and TAU (TAU-AS) for long-term preservation. The enzyme-linked immunoassay and automatic blood cell analyzer were used to detect hemolysis and erythrocyte parameters. Adenine nucleoside triphosphate (ATP), glycerol 2,3-diphosphate (2,3-DPG) and malondialdehyde (MDA) kits were used to test the ATP, 2,3-DPG and MDA concentration.@*RESULTS@#During the preservation, the rate of red blood cell hemolysis in EP-AS and TAU-AS groups were significantly lower than that in CPDA-1 group (P<0.01). The MCV of EP-AS group was increased with the preservation time (r=0.71), while the MCV of the TAU-AS group was significantly lower than that in the other two groups (P<0.05). The concentration of ATP and MDA in EP-AS and TAU-AS groups were significantly higher than that in CPDA-1 group at the 14th day (P<0.01). The concentrations of 2,3-DPG in the EP-AS and TAU-AS groups were significantly higher than that in the CPDA-1 group from the 7th day (P<0.01).@*CONCLUSION@#EP and TAU can significantly reduce the red blood cell hemolysis rate, inhibit the lipid peroxidation level of red blood cells, and improve the energy metabolism of red blood cells during storage. The mechanism of EP and TAU may be related to their antioxidation and membrane protection effect, so as to improve the red blood cell quality and extend the preservation time.

Taurolidina para prevenir infecciones asociadas a catéter venoso central en niños con insuficiencia intestinal: experiencia preliminar en un hospital terciario chileno / Taurolidine for the prevention of catheter-related infections in children with intestinal insufficiency: preliminary experience in a Chilean tertiary hospital

INTRODUCCIÓN: Taurolidina es una molécula con propiedades anti-endotóxicas, antimicrobianas y anti-inflamatorias, que inhibe la adhesión bacteriana, lo que ha permitido usarla como terapia de sellado en catéter venoso central de larga duración (CVC) para prevenir infecciones del torrente sanguíneo asociadas a CVC (ITS-CVC). OBJETIVO: Dar a conocer una experiencia preliminar, la primera en Chile, con taurolidina como terapia de sellado para prevenir ITS-CVC y reportar su eficacia. MÉTODO: Se instiló una solución en base a taurolidina en el CVC de tres niños con insuficiencia intestinal, dependientes de alimentación parenteral, atendidos en un hospital terciario de la Región de Valparaíso, y se comparó la tasa de ITS-CVC antes y después de su uso mediante un análisis retrospectivo. RESULTADOS: en los dos pacientes que iniciaron terapia de sellado inmediatamente después de instalado el CVC, la tasa de ITS-CVC se logró llevar a cero, mientras que, en el tercero, portador de un CVC instalado 9 meses antes, con ITS-CVC recurrentes, un nuevo episodio de ITS-CVC obligó a suspender la profilaxis. CONCLUSIONES: La terapia de sellado con solución en base a taurolidina previno las ITS-CVC cuando ésta se inició al momento de instalarse el CVC, no así en un CVC antiguo con ITS-CVC recurrentes.

BACKGROUND: Taurolidine is a molecule with anti-endotoxic, anti-microbial and anti-inflammatory properties that inhibits bacterial adhesion, allowing for its use as lock therapy for the prevention of catheter-related bloodstream infections (CRBSI) in long-term central venous catheters (CVC). AIM: To report a preliminary experience, the first one in Chile, using lock therapy with taurolidine for the prevention of CRBSI and to report its efficacy. METHOD: A taurolidine-based solution was instilled in the CVC of three children with intestinal insufficiency dependent on parenteral nutrition, attended in a Chilean tertiary hospital, and the rate of CRBSI before and after its use was compared in retrospect. RESULTS: In the two patients who started lock therapy immediately after the installation of their CVC, the rate of CRBSI was brought to zero, whereas in the third patient, who had a 9 months-old CVC with a recurrent CRBSI history, an intercurrent CRBSI forced discontinuation of the prophylaxis. CONCLUSIONS: Lock therapy with a taurolidine-based solution prevented CRBSIs when it was begun immediately after installing the CVC, in contrast with an old CVC with a history of recurrent CRBSIs.

Cardioprotective effect of taurine and ß-alanine against cardiac disease in myocardial ischemia and reperfusion-induced rats

BACKGROUND: The present study analyzed the synergistic protective effect of ß-alanine and taurine against myocardial ischemia/reperfusion. Myocardial infarct size, lipid peroxidation, and levels of glutathione peroxidase (Gpx), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), apoptosis, and the mRNA and protein expression of Janus kinase 2 (JAK2) and signal transducer and activator 3 of transcription (STAT3) were determined. The molecular docking was carried out by using AutoDock 4.2.1. RESULTS: Combined treatment with ß-alanine and taurine reduced myocardial infarct size, lipid peroxidation, inflammatory marker, ROS levels, and apoptosis and increased Gpx, SOD activity, GSH, and catalase activity. Furthermore, combined treatment significantly reduced JAK2 and STAT3 mRNA and protein expression compared with the control. The small molecule was docked over the SH2 domain of a STAT3, and binding mode was determined to investigate the inhibitory potential of ß-alanine and taurine. ß-Alanine bound to SH2 domain with ΔG of -7.34 kcal/mol and KI of 1.91 µM. Taurine bound to SH2 domain with ΔG of -7.38 kcal/mol and KI of 1.95 µM. CONCLUSION: Taken together, these results suggest that the combined supplementation of ß-alanine and taurine should be further investigated as an effective therapeutic approach in achieving cardioprotection in myocardial ischemia/reperfusion.

Knockdown of lncRNA TUG1 inhibits hippocampal neuronal apoptosis and participates in aerobic exercise-alleviated vascular cognitive impairment

OBJECTIVES: Our previous study indicated that aerobic exercise relieves cognitive impairment in patients with vascular cognitive impairment (VCI) via regulating brain-derived neurotrophic factor (BDNF), but the mechanism is not yet clear. This study aimed to explore whether lncRNA taurine upregulated gene 1 (TUG1) participates in the process of VCI by regulating BDNF. METHODS: The expressions of TUG1 and BDNF in the serum of VCI patients were detected. The potential molecular mechanisms of TUG1 in regulating hippocampal neuronal apoptosis were explored in oxygen and glucose deprivation-induced (OGD-induced) hippocampal cell line HT22. The VCI mouse model was established, and TUG1 and BDNF were overexpressed via lentivirus injection. The cognitive impairment of mice was detected by the Morris water maze experiment after the aerobic exercise. RESULTS: The level of TUG1 was elevated in the serum of VCI patients compared with the control group. The knockdown of TUG1 in OGD-induced HT22 cells increased BDNF level and decreased cell apoptosis, and the downregulation of BDNF restored the decreased cell apoptosis. RNA immunoprecipitation and RNA pull-down assays showed that TUG1 could bind to BDNF protein. The aerobic exercise alleviated cognitive impairment and inhibited hippocampal apoptosis in VCI mice. Meanwhile, the overexpression of TUG1 reversed the therapeutic effects of aerobic exercise on cognitive impairment. CONCLUSIONS: The knockdown of TUG1 reduced hippocampal neuronal apoptosis and participates in the aerobic exercise-alleviated VCI, which was partly through regulating BDNF.

lncRNA TUG1 promotes proliferation and differentiation of osteoblasts by regulating the miR-545-3p/CNR2 axis

Osteoblast differentiation is an effective way to promote bone formation. Long non-coding RNA taurine upregulated 1 (TUG1) has been identified as a crucial modulator of multiple biological processes. This study was designed to investigate the function of TUG1 in the proliferation and differentiation of osteoblast precursor cells hFOB1.19. In this study, we found that TUG1 promoted hFOB1.19 cell proliferation, while TUG1 knockdown hindered cell proliferation. TUG1 and cannabinoid receptor 2 (CNR2) were upregulated, while miR-545-3p was down-regulated in hFOB1.19 cells undergoing osteoblastic differentiation. TUG1 induced osteoblast differentiation by increasing alkaline phosphatase (ALP) activity and the expression of osteoblastic differentiation markers. TUG1 was a sponge of miR-545-3p and regulated osteoblastic differentiation by modulating miR-545-3p. Moreover, miR-545-3p directly targeted CNR2 and restored the effect of CNR2 on osteoblastic differentiation. In conclusion, TUG1 accelerated the proliferation and differentiation of osteoblasts by sponging miR-545-3p and increasing CNR2 expression, which might provide a new biomarker for bone diseases.

Taurolidina, un antiséptico para la prevención de infecciones asociadas a catéter venoso central / Taurolidine, an antiseptic for the prevention of central venous catheter-related infections

Resumen Taurolidina es un antiséptico de amplio espectro usado como solución de terapia de sellado (lock therapy) en adultos y niños portadores de catéter venoso central de larga duración (CVC) para prevenir las infecciones asociadas a CVC (IACVC). No induce desarrollo de resistencia y tiene efectos adversos leves y fugaces, lo que lo convierte en una alternativa, tanto como terapia de sellado como para la profilaxis de las IACVC, en este grupo de pacientes.

Taurolidine is a broad-spectrum antiseptic used as lock therapy solution in adult and pediatric patients with long term central venous catheters (CVC) for the prevention of catheter related bloodstream infections (CRBSI). Taurolidine doesn't induce the resistant development and has only minor and brief side effects, which makes it an alternative both as a lock therapy and for the prevention of CRBSI in this group of patients.

Efeitos agudos da ingestão de bebidas energéticas sobre os paramêtros hidro-eletrolíticos durante exercício em esteira / Acute effects of energy drink intake on hydro-electrolytic parameters during the exercise on a treadmill

RESUMO O objetivo do estudo foi verificar se bebidas enegéticas com diferentes composições nutricionais afetam o balanço hidro-eletrolítico de corredores de resistência. Doze homens participaram desse estudo duplo cego e crossover randomizado, ingerindo 3mg.kg-1 de cafeína de bebida energética convencional e sugar free, e um placebo carboidratado e não cafeinado, 40 minutos antes de sessão de exercício em ambiente termoneutro. Em cada situação experimental, os avaliados realizaram exercício de corrida em esteira com duração de 60 minutos e intensidade constante entre 65 e 75% do VO2max, seguidos por um sprint correspondendo a 100% do VO2max até a exaustão. Foram avaliados o peso corporal (PC), desidratação absoluta e relativa, densidade da urina, taxa de sudorese e níveis de Na+, K+ e hematócrito. Durante o exercício os avaliados receberam somente água a cada 15 minutos. Foi verificada alteração nos níveis de densidade da urina antes e depois do exercício para todos os tratamentos (p<0,05). Não houve diferença significativa entre as bebidas nos níveis de Na+, K+ e hematócrito (p>0,05) mantendo-se dentro dos níveis de normalidade. Conclui-se que diferentes tipos de bebidas energéticas não afetam o balanço hidro-eletrolítico de corredores de resistência ao longo do exercício.

ABSTRACT This work compares the effects promoted by energy drinks with diferente nutricional compositions on the hydro-electrolytic balance of resistance runners. Twelve men participated in this double blinded, randomized crossover study, ingesting 3mg*Kg-1 of a conventional energy drink with caffeine or sugar-free, and a placebo 40-minutes before tests on thermoneutral environment. The duration of the session was 60 minutes with constant intensity between 65 and 75% of VO2max, followed by a sprint corresponding to 100% of VO2max until exhaustion. There were evaluated body weight (BW), absolute and relative dehydration, urine density, sweating rate and Na+, K+ and hematocrit levels. During the exercise, the participants drunk only water every 15 minutes. Changes in urine density levels were observed before and after exercise for all procedures (p <0.05). There was no significant difference on the levels of Na+, K+ and hematocrit between the drinks (p> 0.05), remaining within normal levels. It is concluded that different types of energy drinks do not affect the hydro-electrolytic balance of resistance runners during the exercise.

Impact of Taurine on the proliferation and apoptosis of human cervical carcinoma cells and its mechanism / 中华医学杂志(英文版)

BACKGROUND@#Cervical cancer has the fourth highest incidence and mortality rate of all cancers in women worldwide; it seriously harms their physical and mental health. The aim of this study was to observe the roles and preliminary mechanism of Taurine (Tau)-induced apoptosis in cervical cancer cells.@*METHODS@#Cells from the human cervical cancer cell line SiHa were transfected with the recombinant plasmid pEGFP-N1-MST1 (mammalian sterile 20-like kinase 1); then, the cell proliferation activity was analyzed by the MTT assay, cell apoptosis by flow cytometry, and the related protein levels by Western blotting.@*RESULTS@#Tau inhibited the proliferation of SiHa cells and induced apoptosis in these cells (the apoptotic rate was 21.95% in the Tau 160 mmol/L group and 30% in the Tau 320 mmol/L group), upregulated the expression of the MST1 (control, 0.53; Tau 40-320 mmol/L groups, 0.84-1.45) and Bax (control, 0.45; Tau 40-320 mmol/L groups, 0.64-1.51) proteins (P < 0.01), and downregulated the expression of Bcl-2 (control, 1.28, Tau 40-320 mmol/L groups, 0.93-0.47) (P < 0.01). The overexpression of MST1 promoted the apoptosis of SiHa cells, enhanced the apoptosis-inductive effects of Tau (P < 0.01), upregulated the expression of the proapoptotic proteins p73, p53, PUMA (p53 upregulated modulator of apoptosis), and caspase-3, and promoted the phosphorylation of YAP (Yes-associated protein).@*CONCLUSIONS@#Tau inhibited the proliferation and induced the apoptosis of cervical cancer SiHa cells. The MST1 protein plays an important role in the Tau-induced apoptosis of cervical cancer cells.

Chemical profiling for bile acid derivatives in yak bile / 中国中药杂志

Bile acids( BAs),the major constituents of bile,are also known to be potential biomarkers of various diseases,especially liver disease. The systematic analysis of BAs is believed to be of great importance towards the clarification of the effective material basis for bile-type medicines,and the diagnosis and therapy of related diseases as well. As a part of systematic study on bile-type medicine ongoing in our group,this study lays emphasis on the isomer discrimination,and the improvement of analytical method of BAs. Further,this method was subsequently applied to elucidate in depth the chemical profile of BAs in yak bile. Regarding isomer discrimination for BAs,we constructed relative response-collision energy curves( RRCECs) by high performance liquid chromatographyion trap-time of flight-mass spectrometry( HPLC-IT-TOF-MS) in combination with high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry( HPLC-Qtrap-MS). As a result,both the optimum collision energy( OCE) and CE_(50) exhibited great correlations with structural characteristics,thus enabling the isomer distinguishing,such as unconjugated BAs,glycine-conjugated BAs,and taurine-conjugated BAs. According to information provided by mass spectrometry,the comparison of OCE and CE_(50),retention time matching,combined with reference substances and database retrieval,a total of 30 bile acid derivatives were observed and identified in yak bile. The newly developed method could serve as a feasible tool for the in-depth characterization of BAs in bile and biological samples.

Anxiolytic Action of Taurine via Intranasal Administration in Mice

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine’s effect on anxiety. For the characterization of potential mechanism of taurine’s anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine’s anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.

Effects of taurine supplementation in elite swimmers performance

AIM: Taurine is considered a semi-essential amino acid characterized by having various physiological functions in the body that modulate mechanisms of action involved in the muscle contraction process, increased energy expenditure, insulin signaling pathway, carbohydrate metabolism, and scavenging free radicals. These functions are crucial for aerobic exercise performance; thus, taurine supplementation may benefit athletes' performance. The objective of this study was to evaluate the effects of taurine supplementation on the resting energy expenditure and physical performance of swimming athletes. METHODS: In a double-blind study, 14 male swimmers were randomized into two groups: the taurine group (n = 7) and the placebo group (n = 7), which received 3 g per day of taurine or placebo in capsules during 8 weeks. Resting energy expenditure, plasma taurine, physical performance, anthropometry, dietary consumption were measured and an incremental test was performed to determine their maximal front crawl swimming performances before and after the 8-week period. RESULTS: The levels of serum taurine (p < 0.0001) and lactate (p = 0.0130) showed a significant increase in the taurine group; however, the other variables were not different. No changes were observed in the resting energy expenditure, mean speed performed, and the anaerobic threshold of the swimmers post-supplementation period. CONCLUSION: Supplementation of taurine increased plasma concentrations of this amino acid, but did not lead to significant changes in food intake, rest energy expenditure, and athletes' performance. However, the supplemented group presented a higher lactate production, suggesting a possible positive effect of taurine on the anaerobic lactic metabolism.(AU)

Diagnóstico ecocardiográfico e tratamento de cardiomiopatia dilatada em tamanduá- bandeira ( Myrmecophaga trydactila ) mantido em cativeiro: relato de caso / Echocardiographic diagnosis and treatment of dilated cardiomyopathy in captive giant anteater (Myrmecophaga trydactila): case report

A cardiomiopatia dilatada é uma doença de caráter crônico, que compromete a função cardíaca, resultando em desequilíbrio da circulação sanguínea e da homeostase corporal do animal. Este relato apresenta a evolução do quadro clínico e o tratamento de cardiomiopatia dilatada em um exemplar cativo de tamanduá-bandeira. O animal apresentou quadro clínico de insuficiência cardíaca e foi submetido a duas baterias de exames laboratoriais e de imagem em um período de três meses. Posteriormente, foi iniciado o tratamento com pimobendan e suplementação de taurina, resultando em resposta positiva e melhora dos sinais clínicos do paciente. Os achados ecocardiográficos do caso foram compatíveis com cardiomiopatia dilatada com sinais evidentes de diminuição progressiva das frações de ejeção, bem como encurtamento e aumento expressivo das câmaras cardíacas, quando se comparou este caso ao de cães de grande porte e animais saudáveis da mesma espécie. O tratamento com inotrópico positivo, suplementação dietética de taurina e diuréticos se mostrou eficiente em controlar os sinais clínicos do animal.(AU)

The dilated cardiomyopathy it is a chronic disease that leads to a cardiac dysfunction, resulting in unstable blood circulation and specimen body homeostasis. This description shows the dilated cardiomyopathy evolution and treatment in a giant anteater captive model. The patient presented cardiac insufficient clinical condition and was submitted to two sets of laboratorial and image exams in three months. Furthermore, the treatment started with pimobendam and taurine supplementation, leading to satisfactory response to treatment and clinical improvement. The echocardiographic findings were compatible with dilated cardiomyopathy, moreover clear evidence of progressive reduction at the ejection portions and shortening and expressive increase of the cardiac chamber when compared to large dogs and healthy animals of the same species. Treatment with positive inotropic and taurine dietary supplement revealed as effective in clinical managementr.(AU)

Anti-arrhythmic effects of taurine-magnesium coordination compound on torsades de pointes / 中国应用生理学杂志

OBJECTIVES@#To investigate the effect of taurine magnesium coordination compound (TMCC) on torsades de pointes (TdP) in isolated guinea pig hearts.@*METHODS@#Healthy male guinea pigs weighting 250~300 g were randomly divided into 4 groups:①TdP model group (=7):Isolated hearts were perfused by normal K-H solution 20 minutes, then perfused by slowly activated delayed rectifier potassium current(IKs) blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) to establish TdP model;②~④ TdP model + TMCC group (=6):Isolated hearts were perfused by normal K-H solution for 20 minutes, then perfused by IKs blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) for 60 minutes, at the same time TMCC which concentration was 1, 2, 4 mmol/L was administered respectively by Langendorff retrograde aortic perfusion method. Cardiac surface electrocardiogram of guinea pigs was collected and recorded by Biopac electrophysiological recorder. Incidence of TdP, transmural dispersion of repolarization (TDR), instability of QT interval were acquired from Lead Ⅱ electrocardiograph (ECG) wave forms to describe the effect of TMCC on TdP model. Datas were acquired at the time of 20 min and pre-TdP, in case there was no TdP observed, a value of 60 min was entered for calculation purpose.@*RESULTS@#Incidence of TdP in TdP model group was 6/7. TdP incidence could be decreased significantly by 1, 2, 4 mmol/L TMCC, and was 5/6, 1/6, 0/6 respectively. Compared with the pre-drug, Chromanol 293B under hypokalemic solution in TdP model group increased TDR(corrected) evidently(0.05). Compared with the TdP model group, 2, 4 mmol/L TMCC could evidently decrease the instability of QT interval induced by Chromanol 293B under hypokalemic solution(<0.05). During the establishment of TdP model, P waves in more than one cardiac cycle continuously were disappeared in ECG. However, P wave could always be seen independent in ECG acquired from TdP model + TMCC group.@*CONCLUSIONS@#TMCC can play the role against TdP through decreasing TDR and instability of QT interval, and inhibiting early after depolarization(EAD).

Cytoprotective Effect of Taurine against Hydrogen Peroxide-Induced Oxidative Stress in UMR-106 Cells through the Wnt/β-Catenin Signaling Pathway

Osteoporosis development is closely associated with oxidative stress and reactive oxygen species (ROS). Taurine has potential antioxidant effects, but its role in osteoblasts is not clearly understood. The aim of this study was to determine the protective effects and mechanisms of actions of taurine on hydrogen peroxide (H₂O₂)-induced oxidative stress in osteoblast cells. UMR-106 cells were treated with taurine prior to H₂O₂ exposure. After treatment, cell viability, apoptosis, intracellular ROS production, malondialdehyde content, and alkaline phosphate (ALP) activity were measured. We also investigated the protein levels of β-catenin, ERK, CHOP and NF-E2-related factor 2 (Nrf2) along with the mRNA levels of Nrf2 downstream antioxidants. The results showed that pretreatment of taurine could reverse the inhibition of cell viability and suppress the induced apoptosis in a dose-dependent manner: taurine significantly reduced H₂O₂-induced oxidative damage and expression of CHOP, while it induced protein expression of Nrf2 and β-catenin and activated ERK phosphorylation. DKK1, a Wnt/β-catenin signaling inhibitor, significantly suppressed the taurine-induced Nrf2 signaling pathway and increased CHOP. Activation of ERK signaling mediated by taurine in the presence of H₂O₂ was significantly inhibited by DKK1. These data demonstrated that taurine protects osteoblast cells against oxidative damage via Wnt/β-catenin-mediated activation of the ERK signaling pathway.

Age-Related Changes in Sulfur Amino Acid Metabolism in Male C57BL/6 Mice

Alterations in sulfur amino acid metabolism are associated with an increased risk of a number of common late-life diseases, which raises the possibility that metabolism of sulfur amino acids may change with age. The present study was conducted to understand the age-related changes in hepatic metabolism of sulfur amino acids in 2-, 6-, 18- and 30-month-old male C57BL/6 mice. For this purpose, metabolite profiling of sulfur amino acids from methionine to taurine or glutathione (GSH) was performed. The levels of sulfur amino acids and their metabolites were not significantly different among 2-, 6- and 18-month-old mice, except for plasma GSH and hepatic homocysteine. Plasma total GSH and hepatic total homocysteine levels were significantly higher in 2-month-old mice than those in the other age groups. In contrast, 30-month-old mice exhibited increased hepatic methionine and cysteine, compared with all other groups, but decreased hepatic S-adenosylmethionine (SAM), S-adenosylhomocysteine and homocysteine, relative to 2-month-old mice. No differences in hepatic reduced GSH, GSH disulfide, or taurine were observed. The hepatic changes in homocysteine and cysteine may be attributed to upregulation of cystathionine β-synthase and down-regulation of γ-glutamylcysteine ligase in the aged mice. The elevation of hepatic cysteine levels may be involved in the maintenance of hepatic GSH levels. The opposite changes of methionine and SAM suggest that the regulatory role of SAM in hepatic sulfur amino acid metabolism may be impaired in 30-month-old mice.

Effects and Mechanisms of Taurine as a Therapeutic Agent

Taurine is an abundant, β-amino acid with diverse cytoprotective activity. In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. These findings have spurred interest in the potential use of taurine as a therapeutic agent. The discovery that taurine is an effective therapy against congestive heart failure led to the study of taurine as a therapeutic agent against other disease conditions. Today, taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. The present review summarizes studies supporting a role of taurine in the treatment of diseases of muscle, the central nervous system, and the cardiovascular system. In addition, taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis. The review also addresses the functions of taurine (regulation of antioxidation, energy metabolism, gene expression, ER stress, neuromodulation, quality control and calcium homeostasis) underlying these therapeutic actions.

Dietas pós-eclosão suplementadas com fontes de gordura e acrescidas de taurina e glicina sobre a morfometria intestinal e o desempenho de frangos de corte de um a 21 dias / Post-hatch diets supplemented with sources of fat and added taurine and glycine on the intestinal morphology and performance of broilers at 1 to 21 days

O objetivo deste estudo foi avaliar o efeito do fornecimento de dietas pós-eclosão suplementadas com diferentes fontes de gordura insaturada e adicionadas ou não de taurina e glicina sobre o desempenho produtivo, a biometria e a morfometria do intestino delgado de pintos de corte de um a 21 dias de idade. Foram utilizados 480 pintos de corte machos de um dia de idade da linhagem Cobb. O delineamento foi inteiramente ao acaso, em esquema fatorial 2 x 4, com e sem suplementação de taurina e glicina e quatro dietas (controle, óleo de peixe, de soja e de girassol), totalizando oito tratamentos com seis repetições de 10 aves cada. As rações experimentais foram fornecidas de zero a quatro dias de idade. O desempenho zootécnico foi avaliado ao alojamento e aos quatro, sete e 21 dias de idade. Nestas mesmas datas, foram sacrificadas duas aves por unidade experimental para biometria do intestino e histomorfometria da mucosa do intestino. A adição de diferentes fontes de gordura e a suplementação de glicina e taurina às dietas de transição não influenciaram o desempenho produtivo de um a 21 dias. A suplementação das dietas com glicina e taurina alterou a morfologia da mucosa intestinal, principalmente do duodeno, resultando em maior comprimento do vilo e relação vilo:cripta. Entretanto, parte dos efeitos positivos depende do tipo de óleo adicionado, mostrando que dietas pós-eclosão acrescidas de fontes de lipídios podem ser benéficas no desenvolvimento da capacidade funcional do intestino de frangos de corte.(AU)

The aim of this study was to assess post-hatch diets supplemented with different sources of unsaturated fat and added or not with taurine and glycine on the productive performance, biometry and morphology of small intestine of chicks from 1 to 21 days of age. Four hundred and eighty (480) one day old male broiler Cobb chicks were used. The experimental design was completely randomized in a factorial 2 x 4, with and without supplemental taurine and glycine and 4 diets (control, fish, soy and sunflower oil), totaling six treatments with six repetitions of 10 birds each. The experimental diets were supplied from 0 to 4 days old. The performance was evaluated in housing and 4, 7 and 21 days of age. On these same dates, 2 birds per experimental unit were sacrificed for gut biometrics and histomorphometry of intestinal mucosa. The addition of different sources of fat, glycine and taurine supplementation on transition diets did not influence productive performance from 1 to 21 days. Supplementation of diets with glycine and taurine altered the morphology of the intestinal mucosa, mainly of the duodenum, resulting in greater length of villi and villi: crypt ratio. However, the positive effects depend on the type of oil added, showing that post-hatch diets increased with lipid sources may be beneficial in the development of the functional capacity of the intestine of broilers.(AU)

Taurine relaxes human radial artery through potassium channel opening action

The vascular actions and mechanisms of taurine were investigated in the isolated human radial artery (RA). RA rings were suspended in isolated organ baths and tension was recorded isometrically. First, a precontraction was achieved by adding potassium chloride (KCl, 45 mM) or serotonin (5-hydroxytryptamine, 5-HT, 30 µM) to organ baths. When the precontractions were stable, taurine (20, 40, 80 mM) was added cumulatively. Antagonistic effect of taurine on calcium chloride (10 µM to 10 mM)-induced contractions was investigated. Taurine-induced relaxations were also tested in the presence of the K⁺ channel inhibitors tetraethylammonium (1 mM), glibenclamide (10 µM) and 4-aminopyridine (1 mM). Taurine did not affect the basal tone but inhibited the contraction induced by 5-HT and KCl. Calcium chloride-induced contractions were significantly inhibited in the presence of taurine (20, 40, 80 mM) (p<0.05). The relaxation to taurine was inhibited by tetraethylammonium (p<0.05). However, glibenclamide and 4-aminopyridine did not affect taurine-induced relaxations. Present experiments show that taurine inhibits 5-HT and KCl-induced contractions in RA, and suggest that large conductance Ca²⁺-activated K⁺ channels may be involved in taurine-induced relaxation of RA.