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Sample records for hepatic taurine transport

  1. Taurine-Induced Long-Lasting Enhancement of Synaptic Transmission in Mice: Role of Transporters

    PubMed Central

    Sergeeva, O A; Chepkova, A N; Doreulee, N; Eriksson, K S; Poelchen, W; Mönnighoff, I; Heller-Stilb, B; Warskulat, U; Häussinger, D; Haas, H L

    2003-01-01

    Taurine, a major osmolyte in the brain evokes a long-lasting enhancement (LLETAU) of synaptic transmission in hippocampal and cortico-striatal slices. Hippocampal LLETAU was abolished by the GABA uptake blocker nipecotic acid (NPA) but not by the taurine-uptake inhibitor guanidinoethyl sulphonate (GES). Striatal LLETAU was sensitive to GES but not to NPA. Semiquantitative PCR analysis and immunohistochemistry revealed that taurine transporter expression is significantly higher in the striatum than in the hippocampus. Taurine transporter-deficient mice displayed very low taurine levels in both structures and a low ability to develop LLETAU in the striatum, but not in the hippocampus. The different mechanisms of taurine-induced synaptic plasticity may reflect the different vulnerabilities of these brain regions under pathological conditions that are accompanied by osmotic changes such as hepatic encephalopathy. PMID:12824447

  2. Renal transport of taurine adapts to perturbed taurine homeostasis.

    PubMed Central

    Rozen, R; Scriver, C R

    1982-01-01

    Renal adaptation apparently contributes to the homeostasis of taurine, a beta-amino compound that behaves as a conserved metabolite in the mammal. We studied two strains of inbred mice: C3H/HeJ (low-taurine excreter) and C57BL/6J (high-taurine excreter due to impaired basolateral membrane permeability to taurine). Low-protein and low-sulfur amino acid diets fed for two weeks significantly decreased plasma taurine in both strains, decreased fractional taurine excretion in vivo (particularly in the C57BL strain), and increased net uptake of taurine by renal cortex slices and isolated brush-border membrane vesicles (BBMV) in vitro in both strains. Renal adaptation was less obvious in vivo in the low-taurine excreter C3H strain, but in vitro adaptation, as observed in slices and BBMV (P less than 0.01), was greater than that observed in the C57BL strain. Renal cellular taurine content fell (P less than 0.01) only in the adapted C3H strain. The in vitro adaptive response was not confined to taurine; BBMV uptake of D-glucose and L-alanine was also enhanced in the adapted state. Specificity of the stimulus for adaptation was tested with a low-phenylalanine diet; a modest adaptation was observed in vivo and in vitro but only in the C3H strain. BBMV adaptation did not correlate with blood methionine but correlated inversely with plasma taurine (r = 0.71, P less than 0.05), implying that change in extracellular taurine may be a signal for renal adaptation in taurine homeostasis in the mammal. PMID:6952257

  3. Chronic liver disease is triggered by taurine transporter knockout in the mouse.

    PubMed

    Warskulat, Ulrich; Borsch, Elena; Reinehr, Roland; Heller-Stilb, Birgit; Mönnighoff, Irmhild; Buchczyk, Darius; Donner, Markus; Flögel, Ulrich; Kappert, Günther; Soboll, Sibylle; Beer, Sandra; Pfeffer, Klaus; Marschall, Hanns-Ulrich; Gabrielsen, Marcus; Amiry-Moghaddam, Mahmood; Ottersen, Ole Petter; Dienes, Hans Peter; Häussinger, Dieter

    2006-03-01

    Taurine is an abundant organic osmolyte with antioxidant and immunomodulatory properties. Its role in the pathogenesis of chronic liver disease is unknown. The liver phenotype was studied in taurine transporter knockout (taut-/-) mice. Hepatic taurine levels were ~21, 15 and 6 mumol/g liver wet weight in adult wild-type, heterozygous (taut+/-) and homozygous (taut-/-) mice, respectively. Immunoelectronmicroscopy revealed an almost complete depletion of taurine in Kupffer and sinusoidal endothelial cells, but not in parenchymal cells of (taut-/-) mice. Compared with wild-type mice, (taut-/-) and (taut+/-) mice developed moderate unspecific hepatitis and liver fibrosis with increased frequency of neoplastic lesions beyond 1 year of age. Liver disease in (taut-/-) mice was characterized by hepatocyte apoptosis, activation of the CD95 system, elevated plasma TNF-alpha levels, hepatic stellate cell and oval cell proliferation, and severe mitochondrial abnormalities in liver parenchymal cells. Mitochondrial dysfunction was suggested by a significantly lower respiratory control ratio in isolated mitochondria from (taut-/-) mice. Taut knockout had no effect on taurine-conjugated bile acids in bile; however, the relative amount of cholate-conjugates acid was decreased at the expense of 7-keto-cholate-conjugates. In conclusion, taurine deficiency due to defective taurine transport triggers chronic liver disease, which may involve mitochondrial dysfunction. PMID:16421246

  4. Downregulation of taurine transport by calcium blockers in osteoblast cells.

    PubMed

    Kang, Young-Sook

    2009-01-01

    Taurine is found in a high concentration in bone cells and is thought to help enhance bone tissue formation and inhibit bone loss. It is mainly transported by a sodium and chloride ion dependent taurine transporter (TauT), which is expressed in a variety of tissues, such as brain, retina, and placenta, but in bone the transporter has not yet been identified. The purpose of this study is to clarify the uptake mechanism of taurine in osteoblasts using mouse osteoblast cell lines. Mouse stromal ST2 cells and mouse osteoblast-like MC3T3-E1 cells were used as osteoblast cell lines. Detection of TauT mRNA expression in these cells was performed by RT-PCR. The activity of the taurine transporter was assessed by measuring the uptake of [3H]taurine in cell lines in the presence and absence of inhibitors. TauT mRNA was detected in ST2 and MC3T3-E1 cells. [3H]Taurine uptake by these cells exhibited a time dependent increase that was linear for at least 10 min. [3H]Taurine uptake was dependent on the presence of extracellular sodium and chloride ions, and was inhibited by unlabeled taurine, beta-alanine and gamma-amino-n-butyric acid. Moreover, uptake of [3H]taurine by these cells was dependent on the presence of extracellular calcium. The uptake of [3H]taurine in ST2 cells treated with 4 mM calcium was increased 1.7-fold. The initial rate of [3H]taurine uptake was significantly inhibited by 100 microM nifedipine and 100 microM verapamil. These results suggest that in mouse osteoblast cell lines taurine transport is controlled by extracellular calcium. PMID:19239183

  5. GABAA-receptor modification in taurine transporter knockout mice causes striatal disinhibition

    PubMed Central

    Sergeeva, O A; Fleischer, W; Chepkova, A N; Warskulat, U; Häussinger, D; Siebler, M; Haas, H L

    2007-01-01

    The Striatum is involved in the regulation of movements and motor skills. We have shown previously, that the osmolyte and neuromodulator taurine plays a role in striatal plasticity. We demonstrate now that hereditary taurine deficiency in taurine-transporter knock-out (TAUT KO) mice results in disinhibition of striatal network activity, which can be corrected by taurine supplementation. Modification of GABAA but not glycine receptors (taurine is a ligand for both receptor types) underlies this disinhibition. Whole-cell recordings from acutely isolated as well as cultured striatal neurons revealed a decreased agonist sensitivity of the GABAA receptor in TAUT KO neurons in the absence of changes in the maximal GABA-evoked current amplitude. The striatal GABA level in TAUT KO mice was unchanged. The amplitude enhancement of spontaneous IPSCs by zolpidem was stronger in TAUT KO than in wild-type (WT) animals. Tonic inhibition was absent in striatal neurons under control conditions but was detected after incubation with the GABA-transaminase inhibitor vigabatrin: bicuculline induced a larger shift of baseline current in WT as compared to TAUT KO neurons. Lack of taurine leads to reduced sensitivity of synaptic and extrasynaptic GABAA receptors and consequently to disinhibition. These findings help in understanding neuropathologies accompanied by the loss of endogenous taurine, for instance in hepatic encephalopathy. PMID:17962336

  6. Taurine transport in renal brush-border-membrane vesicles.

    PubMed Central

    Rozen, R; Tenenhouse, H S; Scriver, C R

    1979-01-01

    Taurine transport in isolated brush-border-membrane vesicles from rat kidney is concentrative and it is driven by the Na+ gradient and transmembrane potential difference; binding is not a significant component of net uptake. The Na+-dependent component of net uptake is saturable with an apparent Km of 17 microM. The taurine-transport mechanism is selective for beta-amino compounds. PMID:486101

  7. Taurine drinking ameliorates hepatic granuloma and fibrosis in mice infected with Schistosoma japonicum

    PubMed Central

    Yu, Yan-Rong; Ni, Xian-Qiang; Huang, Jie; Zhu, Yong-Hong; Qi, Yong-Fen

    2016-01-01

    In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4+ Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v) for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor β1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response. PMID:27054062

  8. Taurine drinking ameliorates hepatic granuloma and fibrosis in mice infected with Schistosoma japonicum.

    PubMed

    Yu, Yan-Rong; Ni, Xian-Qiang; Huang, Jie; Zhu, Yong-Hong; Qi, Yong-Fen

    2016-04-01

    In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4(+) Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v) for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor β1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response. PMID:27054062

  9. Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised.

    PubMed

    Warskulat, Ulrich; Flögel, Ulrich; Jacoby, Christoph; Hartwig, Hans-Georg; Thewissen, Michael; Merx, Marc W; Molojavyi, Andrej; Heller-Stilb, Birgit; Schrader, Jürgen; Häussinger, Dieter

    2004-03-01

    Taurine is the most abundant free amino acid in heart and skeletal muscle. In the present study, the effects of hereditary taurine deficiency on muscle function were examined in taurine transporter knockout (taut-/-) mice. These mice show an almost complete depletion of heart and skeletal muscle taurine levels. Treadmill experiments demonstrated that total exercise capacity of taut-/- mice was reduced by >80% compared with wild-type controls. The decreased performance of taut-/- mice correlated with increased lactate levels in serum during exercise. Surprisingly, cardiac function of taut-/- mice as assessed by magnetic resonance imaging, echocardiography, and isolated heart studies showed a largely normal phenotype under both control and stimulated conditions. However, analysis of taut-/- skeletal muscle revealed electromyographic abnormalities. (1)H nuclear magnetic resonance spectroscopy of tissue extracts showed that in the heart of taut-/- mice the lack of taurine was compensated by the up-regulation of various organic solutes. In contrast, a deficit of >10 mM in total organic osmolyte concentration was found in skeletal muscle. The present study identifies taurine transport as a crucial factor for the maintenance of skeletal muscle function and total exercise capacity, while cardiac muscle apparently can compensate for the loss of taurine. PMID:14734644

  10. Expression and functional analysis of mussel taurine transporter, as a key molecule in cellular osmoconforming.

    PubMed

    Hosoi, Masatomi; Takeuchi, Kazuharu; Sawada, Hideki; Toyohara, Haruhiko

    2005-11-01

    Most aquatic invertebrates adapt to environmental osmotic changes primarily by the cellular osmoconforming process, in which osmolytes accumulated in their cells play an essential role. Taurine is one of the most widely utilized osmolytes and the most abundant in many molluscs. Here, we report the structure, function and expression of the taurine transporter in the Mediterranean blue mussel (muTAUT), as a key molecule in the cellular osmoconforming process. Deduced amino acid sequence identity among muTAUT and vertebrate taurine transporters is lower (47-51%) than that among vertebrate taurine transporters (>78%). muTAUT has a lower affinity and specificity for taurine and a requirement for higher NaCl concentration than vertebrate taurine transporters. This seems to reflect the internal environment of the mussel; higher NaCl and taurine concentrations. In addition to the hyperosmotic induction that has been reported for cloned taurine transporters, the increase in muTAUT mRNA was unexpectedly observed under hypoosmolality, which was depressed by the addition of taurine to ambient seawater. In view of the decrease in taurine content in mussel tissue under conditions of hypoosmolality reported previously, our results lead to the conclusion that muTAUT does not respond directly to hypoosmolality, but to the consequent decrease in taurine content. By immunohistochemistry, intensive expression of muTAUT was observed in the gill and epithelium of the mantle, which were directly exposed to intensive osmotic changes of ambient seawater. PMID:16272243

  11. Osmoregulated taurine transport in H4IIE hepatoma cells and perfused rat liver.

    PubMed Central

    Warskulat, U; Wettstein, M; Häussinger, D

    1997-01-01

    The effects of aniso-osmotic exposure on taurine transport were studied in H4IIE rat hepatoma cells. Hyperosmotic (405 mosmol/l) exposure of H4IIE cells stimulated Na+-dependent taurine uptake and led to an increase in taurine transporter (TAUT) mRNA levels, whereas hypo-osmotic (205 mosmol/l) exposure diminished both taurine uptake and TAUT mRNA levels when compared with normo-osmotic (305 mosmol/l) control incubations. Taurine uptake increased 30-40-fold upon raising the ambient osmolarity from 205 to 405 mosmol/l. When H4IIE cells and perfused livers were preloaded with taurine, hypo-osmotic cell swelling led to a rapid release of taurine from the cells. The taurine efflux, but not taurine uptake, was sensitive to 4,4'-di-isothiocyanatostilbene-2,2'-disulphonic acid (DIDS), suggestive of an involvement of DIDS-sensitive channels in mediating volume-regulatory taurine efflux. Whereas in both H4IIE rat hepatoma cells and primary hepatocytes TAUT mRNA levels were strongly dependent upon ambient osmolarity, mRNAs for other osmolyte transporters, i.e. the betaine transporter BGT-1 and the Na+/myo-inositol transporter SMIT, were not detectable. In line with this, myo-inositol uptake by H4IIE hepatoma cells was low and was not stimulated by hyperosmolarity. However, despite the absence of BGT-1 mRNA, a slight osmosensitive uptake of betaine was observed, but the rate was less than 10% of that of taurine transport. This study identifies a constitutively expressed and osmosensitive TAUT in H4IIE cells and the use of taurine as a main osmolyte, whereas betaine and myo-inositol play little or no role in the osmolyte strategy in these cells. This is in contrast with rat liver macrophages, in which betaine has been shown to be a major osmolyte. PMID:9032454

  12. Sulfasalazine-induced renal and hepatic injury in rats and the protective role of taurine

    PubMed Central

    Heidari, Reza; Rasti, Maryam; Shirazi Yeganeh, Babak; Niknahad, Hossein; Saeedi, Arastoo; Najibi, Asma

    2016-01-01

    Introduction: Sulfasalazine is a drug commonly administrated against inflammatory-based disorders. On the other hand, kidney and liver injury are serious adverse events accompanied by sulfasalazine administration. No specific therapeutic option is available against this complication. The current investigation was designed to evaluate the potential protective effects of taurine against sulfasalazine-induced kidney and liver injury in rats. Methods: Male Sprague-Dawley rats were administered with sulfasalazine (600 mg/kg, oral) for 14 consecutive days. Animals received different doses of taurine (250, 500 and 1000 mg/ kg, i.p.) every day. Markers of organ injury were evaluated on day 15th, 24 h after the last dose of sulfasalazine. Results: Sulfasalazine caused renal and hepatic injury as judged by an increase in serum level of creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP). The levels of reactive oxygen species (ROS) and lipid peroxidation were raised in kidney and liver of sulfasalazine-treated animals. Moreover, tissue glutathione reservoirs were depleted after sulfasalazine administration. Histopathological changes of kidney and liver also endorsed organ injury. Taurine administration (250, 500 and 1000 mg/kg/day, i.p) alleviated sulfasalazine-induced renal and hepatic damage. Conclusion: Taurine administration could serve as a potential protective agent with therapeutic capabilities against sulfasalazine adverse effects. PMID:27340618

  13. Taurine transporter in lymphocytes of patients with major depression treated with venlafaxine plus psychotherapy.

    PubMed

    Fazzino, Fili; Obregón, Francisco; Morles, Margarita; Rojas, Andrés; Arocha, Luis; Mata, Salvador; Lima, Lucimey

    2009-01-01

    The taurine transporter and taurine are present in lymphocytes, where taurine functions as an antioxidant and an anti-inflammatory agent. Taurine levels are elevated in lymphocytes of subjects with major depression, but returns to control levels after treatment with the antidepressant mirtazapine. Patients (40) were diagnosed using the Diagnostic and Statistical Manual IV of the American Psychiatric Association, and the severity of their condition was determined by the Hamilton Scale of Depression. One group of patients was treated with venlafaxine and the other with venlafaxine plus Neuro-Linguistic Programming. Lymphocytes were isolated from the peripheral blood by Ficoll/Hypaque. The coexistence of the taurine transporter with a subpopulation of CD4+ and CD8+ lymphocytes was measured by immunofluorescence. The levels of the pro-inflammatory, IL-2, and the anti-inflammatory, IL-4, cytokines were determined by ELISA while plasma amino acid levels were determined by HPLC. The percentage of CD4+ cells significantly decreased after both treatments, whereas the levels of CD8+ cells remained unchanged. The taurine transporter of CD4+ and CD8+ cells decreased after integrate treatment. No differences were found in the levels of IL-2 while IL-4 levels increased after integrate treatment. The observed effects of treatment on the taurine transporter and IL-4 content might modify lymphocyte activity during depression. PMID:19239152

  14. Cysteine Sulfinic Acid Decarboxylase Regulation: A Role for FXR and SHP in Murine Hepatic Taurine Metabolism

    PubMed Central

    Kerr, Thomas A.; Matsumoto, Yuri; Matsumoto, Hitoshi; Xie, Yan; Hirschberger, Lawrence L.; Stipanuk, Martha H.; Anakk, Sayeepriyadarshini; Moore, David D.; Watanabe, Mitsuhiro; Kennedy, Susan

    2014-01-01

    Background Bile acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor15/19 (FGF15/19). Because bile acid synthesis involves amino acid conjugation, we hypothesized that hepatic cysteine sulfinic acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile acids. Aims To investigate CSAD regulation by bile acids and CSAD regulatory mechanisms. Methods Mice were fed a control diet or a diet supplemented with either 0.5% cholate or 2% cholestyramine. To gain mechanistic insight into CSAD regulation, we utilized GW4064 (FXR agonist), FGF19, or T-0901317 (LXR agonist) and Shp−/− mice. Tissue mRNA expression was determined by qRT-PCR. Amino acids were measured by HPLC. Results Mice supplemented with dietary cholate exhibited reduced hepatic CSAD mRNA expression while those receiving cholestyramine exhibited increased hepatic CSAD mRNA expression. Activation of FXR suppressed CSAD mRNA expression whereas hepatic CSAD mRNA expression was increased in Shp−/− mice. Hepatic hypotaurine concentration (the product of CSAD) was higher in Shp−/− mice with a corresponding increase in serum (but not hepatic) taurine-conjugated bile acids. FGF19 administration suppressed hepatic CYP7A1 mRNA but did not change CSAD mRNA expression. LXR activation induced CYP7A1 mRNA yet failed to induce CSAD mRNA expression. Conclusion CSAD mRNA expression is physiologically regulated by bile acids in a feedback fashion via mechanisms involving SHP and FXR but not FGF15/19 or LXR. These novel findings implicate bile acids as regulators of CSAD mRNA via mechanisms shared in part with CYP7A1. PMID:24033844

  15. Characterization of a Carrier-Mediated Transport System for Taurine in the Fetal Mouse Heart In Vitro

    PubMed Central

    Grosso, David S.; Roeske, William R.; Bressler, Rubin

    1978-01-01

    Cardiac taurine levels are elevated in hypertension and congestive heart failure. A possible mechanism for this increase in taurine is an alteration of its uptake. We sought to identify and characterize a carrier-mediated transport system for taurine in the mammalian myocardium utilizing the fetal mouse heart in organ culture. Hearts from fetuses of 16-19 days gestational age used in these studies had an endogenous taurine content of 14.1±0.5 nmol/mg tissue. The uptake of [3H]taurine was linear for up to 8 h. Taurine was accumulated against a concentration gradient as demonstrated by a net increase in taurine concentration when hearts were incubated in 0.5 mM taurine. [3H]Taurine uptake was saturable, Km = 0.44 mM, temperature dependent, and required sodium. The close structural analogues, hypotaurine and β-alanine, reduced [3H]taurine uptake by 87% when present in 100-fold excess. The α-amino acids alanine, α-aminoisobutyric acid, glycine, leucine, and threonine did not inhibit uptake. Other taurine analogues tested were guanidinotaurine, guanidinopropionic acid, γ-aminobutyric acid, 2-aminoethane phosphonic acid, aminomethane sulfonic acid, 3-aminopropane sulfonic acid, N-acetyltaurine, and isethionic acid. We conclude that a carrier-mediated transport system for taurine exists in the fetal mouse heart based on the demonstration of (a) temperature dependence, (b) saturability, and (c) structural selectivity of the uptake process. Transport was demonstrated to be mediated by a β-amino acid uptake system. In addition, taurine uptake was observed to be sodium dependent, energy dependent, and capable of accumulating taurine against a concentration gradient. PMID:659583

  16. Extrahepatic tissues compensate for loss of hepatic taurine synthesis in mice with liver-specific knockout of cysteine dioxygenase.

    PubMed

    Ueki, Iori; Roman, Heather B; Hirschberger, Lawrence L; Junior, Carolyn; Stipanuk, Martha H

    2012-05-01

    Because hepatic cysteine dioxygenase (CDO) appears to play the major role in controlling cysteine catabolism in the intact rat, we characterized the effect of a lack of hepatic CDO on the regulation of cysteine and its metabolites at the whole body level. In mice with liver-specific deletion of CDO expression, hepatic and plasma cysteine levels increased. In addition, in mice with liver-specific deletion of CDO expression, the abundance of CDO and the proportion of CDO existing as the mature, more active isoform increased in extrahepatic tissues that express CDO (kidney, brown fat, and gonadal fat). CDO abundance was also increased in the pancreas, where most of the enzyme in both control and liver CDO-knockout mice was in the more active isoform. This upregulation of CDO concentration and active-site cofactor formation were not associated with an increase in CDO mRNA and thus presumably were due to a decrease in CDO degradation and an increase in CDO cofactor formation in association with increased exposure of extrahepatic tissues to cysteine in mice lacking hepatic CDO. Extrahepatic tissues of liver CDO-knockout mice also had higher levels of hypotaurine, consistent with increased metabolism of cysteine by the CDO/cysteinesulfinate decarboxylase pathway. The hepatic CDO-knockout mice were able to maintain normal levels of glutathione, taurine, and sulfate. The maintenance of taurine concentrations in liver as well as in extrahepatic tissues is particularly notable, since mice were fed a taurine-free diet and liver is normally considered the major site of taurine biosynthesis. This redundant capacity for regulation of cysteine concentrations and production of hypotaurine/taurine is additional support for the body's robust mechanisms for control of body cysteine levels and indicates that extrahepatic tissues are able to compensate for a lack of hepatic capacity for cysteine catabolism. PMID:22414809

  17. Effects of Taurine Supplementation on Hepatic Markers of Inflammation and Lipid Metabolism in Mothers and Offspring in the Setting of Maternal Obesity

    PubMed Central

    Li, Minglan; Reynolds, Clare M.; Sloboda, Deborah M.; Gray, Clint; Vickers, Mark H.

    2013-01-01

    Maternal obesity is associated with obesity and metabolic disorders in offspring. However, intervention strategies to reverse or ameliorate the effects of maternal obesity on offspring health are limited. Following maternal undernutrition, taurine supplementation can improve outcomes in offspring, possibly via effects on glucose homeostasis and insulin secretion. The effects of taurine in mediating inflammatory processes as a protective mechanism has not been investigated. Further, the efficacy of taurine supplementation in the setting of maternal obesity is not known. Using a model of maternal obesity, we examined the effects of maternal taurine supplementation on outcomes related to inflammation and lipid metabolism in mothers and neonates. Time-mated Wistar rats were randomised to either: 1) control : control diet during pregnancy and lactation (CON); 2) CON supplemented with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (high fat, high fructose) during pregnancy and lactation (MO); or 4) MO supplemented with taurine (MOT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analysed. A MO diet resulted in maternal hyperinsulinemia and hyperleptinemia and increased plasma glucose, glutamate and TNF-α concentrations. Taurine normalised maternal plasma TNF-α and glutamate concentrations in MOT animals. Both MO and MOT mothers displayed evidence of fatty liver accompanied by alterations in key markers of hepatic lipid metabolism. MO neonates displayed a pro-inflammatory hepatic profile which was partially rescued in MOT offspring. Conversely, a pro-inflammatory phenotype was observed in MOT mothers suggesting a possible maternal trade-off to protect the neonate. Despite protective effects of taurine in MOT offspring, neonatal mortality was increased in CT neonates, indicating possible adverse effects of taurine in the setting of normal pregnancy. These data suggest that maternal taurine supplementation may

  18. Maternal obesity is associated with a reduction in placental taurine transporter activity

    PubMed Central

    Ditchfield, A M; Desforges, M; Mills, T A; Glazier, J D; Wareing, M; Mynett, K; Sibley, C P; Greenwood, S L

    2015-01-01

    Background/Objectives: Maternal obesity increases the risk of poor pregnancy outcome including stillbirth, pre-eclampsia, fetal growth restriction and fetal overgrowth. These pregnancy complications are associated with dysfunctional syncytiotrophoblast, the transporting epithelium of the human placenta. Taurine, a β-amino acid with antioxidant and cytoprotective properties, has a role in syncytiotrophoblast development and function and is required for fetal growth and organ development. Taurine is conditionally essential in pregnancy and fetal tissues depend on uptake of taurine from maternal blood. We tested the hypothesis that taurine uptake into placental syncytiotrophoblast by the taurine transporter protein (TauT) is lower in obese women (body mass index (BMI)⩾30 kg m−2) than in women of ideal weight (BMI 18.5–24.9 kg m−2) and explored potential regulatory factors. Subjects/Methods: Placentas were collected from term (37–42-week gestation), uncomplicated, singleton pregnancies from women with BMI 19–49 kg m−2. TauT activity was measured as the Na+-dependent uptake of 3H-taurine into placental villous fragments. TauT expression in membrane-enriched placental samples was investigated by western blot. In vitro studies using placental villous explants examined whether leptin or IL-6, adipokines/cytokines that are elevated in maternal obesity, regulates TauT activity. Results: Placental TauT activity was significantly lower in obese women (BMI⩾30) than women of ideal weight (P<0.03) and inversely related to maternal BMI (19–49 kg m−2; P<0.05; n=61). There was no difference in TauT expression between placentas of ideal weight and obese class III (BMI⩾40) subjects. Long-term exposure (48 h) of placental villous explants to leptin or IL-6 did not affect TauT activity. Conclusions: Placental TauT activity at term is negatively related to maternal BMI. We propose that the reduction in placental TauT activity in maternal obesity

  19. The role of taurine in infant nutrition.

    PubMed

    Chesney, R W; Helms, R A; Christensen, M; Budreau, A M; Han, X; Sturman, J A

    1998-01-01

    The importance of taurine in the diet of pre-term and term infants has not always been clearly understood and is a topic of interest to students of infant nutrition. Recent evidence indicates that it should be considered one of the "conditionally essential" amino acids in infant nutrition. Plasma values for taurine will fall if infants are fed a taurine-free formula or do not have taurine provided in the TPN solution. Urine taurine values also fall, which is indicative of an attempt by the kidney to conserve taurine. The very-low-birth-weight infant, for a variety of reasons involving the maturation of tubular transport function, cannot maximally conserve taurine by enhancing renal reabsorption and, hence, is potentially at greater risk for taurine depletion than larger pre-term or term infants, and certainly more than older children who have taurine in their diet. Taurine has an important role in fat absorption in pre-term and possibly term infants and in children with cystic fibrosis. Because taurine-conjugated bile acids are better emulsifiers of fat than glycine-conjugated bile acids, the dietary (or TPN) intake has a direct influence on absorption of lipids. Taurine supplementation of formulas or TPN solutions could potentially serve to minimize the brain phospholipid fatty acid composition differences between formula-fed and human milk-fed infants. Taurine appears to have a role in infants, children, and even adults receiving most (> 75%) of their calories from TPN solutions in the prevention of granulation of the retina and electroencephalographic changes. Taurine has also been reported to improve maturation of auditory-evoked responses in pre-term infants, although this point is not fully established. Clearly, taurine is an important osmolyte in the brain and the renal medulla. At these locations, it is a primary factor in the cell volume regulatory process, in which brain or renal cells swell or shrink in response to osmolar changes, but return to their

  20. Transcriptomic and proteomic analysis of human hepatic stellate cells treated with natural taurine.

    PubMed

    Liang, Jian; Deng, Xin; Wu, Fa-Sheng; Tang, Yan-Fang

    2013-05-01

    The aim of this study was to investigate the differential expression of genes and proteins between natural taurine (NTau)‑treated hepatic stellate cells (HSCs) and control cells as well as the underlying mechanism of NTau in inhibiting hepatic fibrosis. A microculture tetrazolium (MTT) assay was used to analyze the proliferation of NTau‑treated HSCs. Flow cytometry was performed to compare the apoptosis rate between NTau-treated and non‑treated HSCs. Proteomic analysis using a combination of 2-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) was conducted to identify the differentially expressed proteins. Microarray analysis was performed to investigate the differential expression of genes and real-time polymerase chain reaction (PCR) was used to validate the results. The experimental findings obtained demonstrated that NTau decreased HSC proliferation, resulting in an increased number of cells in the G0/G1 phase and a reduced number of cells in the S phase. Flow cytometric analysis showed that NTau-treated HSCs had a significantly increased rate of apoptosis when compared with the non‑treated control group. A total of 15 differentially expressed proteins and 658 differentially expressed genes were identified by 2DE and MS, and microarray analysis, respectively. Gene ontology (GO) functional analysis indicated that these genes and proteins were enriched in the function clusters and pathways related to cell proliferation, cellular apoptosis and oxidation. The transcriptome and proteome analyses of NTau-treated HSCs demonstrated that NTau is able to significantly inhibit cell proliferation and promote cell apoptosis, highlighting its potential therapeutic benefits in the treatment of hepatic fibrosis. PMID:23525364

  1. Characteristics of taurine transport in cultured renal epithelial cell lines: asymmetric polarity of proximal and distal cell lines.

    PubMed

    Jones, D P; Miller, L A; Budreau, A; Chesney, R W

    1992-01-01

    Taurine transport was determined in two continuous, renal epithelial cell lines: LLC-PK1 derived from the proximal tubule of the pig, and the Madin-Darby canine kidney cell (MDCK) from the distal tubule of the dog. In LLC-PK1, taurine transport is maximal at the apical surface, whereas in MDCK cells, transport is greatest at the basolateral surface. Transport is highly dependent on both sodium and chloride in the external medium, and is specific for beta-amino acids. The apical and basolateral surfaces of both cell lines show an adaptive response to extracellular taurine concentration, but only the basolateral surface of the MDCK cell responds to hyperosomolality by increased taurine accumulation. Thus, differential control of the beta-amino acid transport system by substrate and external tonicity exists. The role of the beta-amino acid transport system may differ according to the origin of the cell: in the proximal renal tubular cell, net transepithelial reabsorption of filtered taurine increases the body pool. By contrast, taurine accumulation by distal tubular cells may form a mechanism of cell volume regulation in response to osmotic stress. PMID:1509959

  2. Taurine and platelet aggregation

    SciTech Connect

    Nauss-Karol, C.; VanderWende, C.; Gaut, Z.N.

    1986-03-01

    Taurine is a putative neurotransmitter or neuromodulator. The endogenous taurine concentration in human platelets, determined by amino acid analysis, is 15 ..mu..M/g. In spite of this high level, taurine is actively accumulated. Uptake is saturable, Na/sup +/ and temperature dependent, and suppressed by metabolic inhibitors, structural analogues, and several classes of centrally active substances. High, medium and low affinity transport processes have been characterized, and the platelet may represent a model system for taurine transport in the CNS. When platelets were incubated with /sup 14/C-taurine for 30 minutes, then resuspended in fresh medium and reincubated for one hour, essentially all of the taurine was retained within the cells. Taurine, at concentrations ranging from 10-1000 ..mu..M, had no effect on platelet aggregation induced by ADP or epinephrine. However, taurine may have a role in platelet aggregation since 35-39% of the taurine taken up by human platelets appears to be secreted during the release reaction induced by low concentrations of either epinephrine or ADP, respectively. This release phenomenon would imply that part of the taurine taken up is stored directly in the dense bodies of the platelet.

  3. Downregulation of the taurine transporter TauT during hypo-osmotic stress in NIH3T3 mouse fibroblasts.

    PubMed

    Hansen, Daniel Bloch; Friis, Martin Barfred; Hoffmann, Else Kay; Lambert, Ian Henry

    2012-02-01

    The present work was initiated to investigate regulation of the taurine transporter TauT by reactive oxygen species (ROS) and the tonicity-responsive enhancer binding protein (TonEBP) in NIH3T3 mouse fibroblasts during acute and long-term (4 h) exposure to low-sodium/hypo-osmotic stress. Taurine influx is reduced following reduction in osmolarity, keeping the extracellular Na(+) concentration constant. TonEBP activity is unaltered, whereas TauT transcription as well as TauT activity are significantly reduced under hypo-osmotic conditions. In contrast, TonEBP activity and TauT transcription are significantly increased following hyperosmotic exposure. Swelling-induced ROS production in NIH3T3 fibroblasts is generated by NOX4 and by increasing total ROS, by either exogenous application of H(2)O(2) or overexpressing NOX4, we demonstrate that TonEBP activity and taurine influx are regulated negatively by ROS under hypo-osmotic, low-sodium conditions, whereas the TauT mRNA level is unaffected. Acute exposure to ROS reduces taurine uptake as a result of modulated TauT transport kinetics. Thus, swelling-induced ROS production could account for the reduced taurine uptake under low-sodium/hypo-osmotic conditions by direct modulation of TauT. PMID:22383044

  4. Antioxidant and hepatic protective effects of lotus root hot water extract with taurine supplementation in rats fed a high fat diet

    PubMed Central

    2010-01-01

    Background Nelumbo nucifera, known as sacred lotus, is a well-known medicinal plant and this lotus root is commonly used as food compared to different parts of this plant. This study was conducted to investigate the antioxidant and hepatic protective effects of lotus root hot water extract with taurine supplementation in high fat diet-induced obese rats. Methods Thirty-two male Sprague-Dawley rats (4-week-old) were randomly divided into four groups (n=8) for 6 weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus root hot water extract, HFR group; high fat diet + lotus root hot water extract + taurine, HFRT group). Lotus root hot water extract was orally administrated (400mg/kg/day) to HFR and HFRT groups and the same amount of distilled water was orally administered to N and HF groups. Taurine was supplemented by dissolving in feed water (3% w/v). Results The activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum were lower in HFR and HFRT groups compared to HF group. Thiobarbituric acid reactive substance contents in all groups fed a high fat diet were higher compared to N group. The activities of hepatic antioxidant enzymes were higher in HFR and HFRT groups compared to HF group. Conclusions These results suggest that lotus root hot water extract with taurine supplementation shows antioxidant and hepatic protective effects in high fat diet-induced obese rats. PMID:20804615

  5. Changes in Hepatic Gene Expression upon Oral Administration of Taurine-Conjugated Ursodeoxycholic Acid in ob/ob Mice

    PubMed Central

    Jeon, Jouhyun; Park, Ho Sun; Kang, Gyeong Hoon; Park, Kyong Soo; Lee, Hong Kyu; Kim, Sanguk; Cho, Young Min

    2010-01-01

    Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and associated with considerable morbidities. Unfortunately, there is no currently available drug established to treat NAFLD. It was recently reported that intraperitoneal administration of taurine-conjugated ursodeoxycholic acid (TUDCA) improved hepatic steatosis in ob/ob mice. We hereby examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER) stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice. Compared to the control ob/ob mice, TUDCA treated ob/ob mice revealed markedly reduced liver fat stained by oil red O (44.2±5.8% vs. 21.1±10.4%, P<0.05), whereas there was no difference in body weight, oral glucose tolerance, insulin sensitivity, and ER stress. Microarray analysis of hepatic gene expression demonstrated that oral TUDCA treatment mainly decreased the expression of genes involved in de novo lipogenesis among the components of lipid homeostasis. At pathway levels, oral TUDCA altered the genes regulating amino acid, carbohydrate, and drug metabolism in addition to lipid metabolism. In summary, oral TUDCA treatment decreased hepatic steatosis in ob/ob mice by cooperative regulation of multiple metabolic pathways, particularly by reducing the expression of genes known to regulate de novo lipogenesis. PMID:21079772

  6. Protective Role of Taurine against Arsenic-Induced Mitochondria-Dependent Hepatic Apoptosis via the Inhibition of PKCδ-JNK Pathway

    PubMed Central

    Das, Joydeep; Ghosh, Jyotirmoy; Manna, Prasenjit; Sil, Parames C.

    2010-01-01

    Background Oxidative stress-mediated hepatotoxic effect of arsenic (As) is mainly due to the depletion of glutathione (GSH) in liver. Taurine, on the other hand, enhances intracellular production of GSH. Little is known about the mechanism of the beneficial role of taurine in As-induced hepatic pathophysiology. Therefore, in the present study we investigated its beneficial role in As-induced hepatic cell death via mitochondria-mediated pathway. Methodology/Principal Findings Rats were exposed to NaAsO2 (2 mg/kg body weight for 6 months) and the hepatic tissue was used for oxidative stress measurements. In addition, the pathophysiologic effect of NaAsO2 (10 µM) on hepatocytes was evaluated by determining cell viability, mitochondrial membrane potential and ROS generation. As caused mitochondrial injury by increased oxidative stress and reciprocal regulation of Bcl-2, Bcl-xL/Bad, Bax, Bim in association with increased level of Apaf-1, activation of caspase 9/3, cleavage of PARP protein and ultimately led to apoptotic cell death. In addition, As markedly increased JNK and p38 phosphorylation with minimal disturbance of ERK. Pre-exposure of hepatocytes to a JNK inhibitor SP600125 prevented As-induced caspase-3 activation, ROS production and loss in cell viability. Pre-exposure of hepatocytes to a p38 inhibitor SB2035, on the other hand, had practically no effect on these events. Besides, As activated PKCδ and pre-treatment of hepatocytes with its inhibitor, rottlerin, suppressed the activation of JNK indicating that PKCδ is involved in As-induced JNK activation and mitochondrial dependent apoptosis. Oral administration of taurine (50 mg/kg body weight for 2 weeks) both pre and post to NaAsO2 exposure or incubation of the hepatocytes with taurine (25 mM) were found to be effective in counteracting As-induced oxidative stress and apoptosis. Conclusions/Significance Results indicate that taurine treatment improved As-induced hepatic damages by inhibiting PKC

  7. Combination therapy with taurine, epigallocatechin gallate and genistein for protection against hepatic fibrosis induced by alcohol in rats.

    PubMed

    Zhuo, Lang; Liao, Ming; Zheng, Li; He, Min; Huang, Quanfang; Wei, Ling; Huang, Renbin; Zhang, Shijun; Lin, Xing

    2012-01-01

    This study was to investigate the possibility of enhancing the anti-fibrotic effect by using a combination therapy with taurine, epigallocatechin gallate and genistein in a rat liver fibrosis model induced by alcohol, and to explore its underlying mechanism. Hepatic fibrosis was induced by intragastric administration with various amount of alcohol (5.0-9.5 g/kg) within 24 weeks in rats. The model group received alcohol only, and treatment groups received the corresponding drugs plus alcohol respectively, while the normal control group received an equal volume of saline. The antifibrotic effects of combination therapy were assessed directly by hepatic histology, and indirectly by measurement of serum biochemical markers, the fibrosis markers and related key cytokines/proteins. The results showed that combination therapy could significantly improve the liver function, as indicated by decreasing levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyltransferase, interleukin-6 and tumor necrosis factor-α. Moreover, combination therapy could effectively suppress the serum levels of fibrosis markers and hepatic hydroxyproline content, inhibit collagen deposition and reduce the pathological tissue damage. Research on mechanism showed that combination therapy was able to markedly reduce lipid peroxidation and recruit the anti-oxidative defense system, and inhibit the expression of B-cell lymphoma 2, α-smooth muscle actin, transforming growth factor β(1) and small mothers against decapentaplegic homolog 3 proteins. Our results showed that combination therapy is effective in attenuating hepatic injury and fibrosis in the alcohol-induced rat model. The improved efficacy of the combination therapy with its good safety profile could represent a new protective approach for liver fibrosis. PMID:23037169

  8. Deletion of the γ-aminobutyric acid transporter 2 (GAT2 and SLC6A13) gene in mice leads to changes in liver and brain taurine contents.

    PubMed

    Zhou, Yun; Holmseth, Silvia; Guo, Caiying; Hassel, Bjørnar; Höfner, Georg; Huitfeldt, Henrik S; Wanner, Klaus T; Danbolt, Niels C

    2012-10-12

    The GABA transporters (GAT1, GAT2, GAT3, and BGT1) have mostly been discussed in relation to their potential roles in controlling the action of transmitter GABA in the nervous system. We have generated the first mice lacking the GAT2 (slc6a13) gene. Deletion of GAT2 (both mRNA and protein) neither affected growth, fertility, nor life span under nonchallenging rearing conditions. Immunocytochemistry showed that the GAT2 protein was predominantly expressed in the plasma membranes of periportal hepatocytes and in the basolateral membranes of proximal tubules in the renal cortex. This was validated by processing tissue from wild-type and knockout mice in parallel. Deletion of GAT2 reduced liver taurine levels by 50%, without affecting the expression of the taurine transporter TAUT. These results suggest an important role for GAT2 in taurine uptake from portal blood into liver. In support of this notion, GAT2-transfected HEK293 cells transported [(3)H]taurine. Furthermore, most of the uptake of [(3)H]GABA by cultured rat hepatocytes was due to GAT2, and this uptake was inhibited by taurine. GAT2 was not detected in brain parenchyma proper, excluding a role in GABA inactivation. It was, however, expressed in the leptomeninges and in a subpopulation of brain blood vessels. Deletion of GAT2 increased brain taurine levels by 20%, suggesting a taurine-exporting role for GAT2 in the brain. PMID:22896705

  9. Taurine and vitamin E supplementations have minimal effects on body composition, hepatic lipids, and blood hormone and metabolite concentrations in healthy Sprague Dawley rats

    PubMed Central

    Allen, Portia S; Brown, Andrew W; Brown, Michelle M Bohan; Hsu, Walter H; Beitz, Donald C

    2015-01-01

    Background As prescriptions for off-label pharmaceutical use and autonomous administration of over-the-counter nutraceuticals become mainstream, thorough assessments of these compounds are warranted. Objective To determine the effects of gemfibrozil, rosiglitazone, metformin, taurine, and vitamin E on body composition, hepatic lipids, and metabolic hormone and blood metabolite concentrations in a healthy, outbred rat cohort. Methods Male Sprague Dawley rats were fed a purified 10 kcal% from fat diet for 56 days and assigned to diet alone (control) or diet plus oral administration of gemfibrozil (34 mg/kg), metformin (500 mg/kg), rosiglitazone (3 mg/kg), taurine (520 mg/kg), or vitamin E (200 mg/kg). Results Rosiglitazone administration resulted in a 56% increase in carcass adiposity, cautioning potential prescriptive off-label use. Taurine supplementation had no adverse effects on evaluated parameters. A modest but significant increase in liver triacylglycerol content was observed with vitamin E supplementation compared with control (Δ 17.2 g triacylglycerol/100 g liver lipid). Conclusions The evaluated pharmaceuticals had effects in a healthy population similar to the reported effects in their target population and the nutraceuticals had minimal effects on the measured physiological parameters. PMID:26752960

  10. Taurine and fish development: insights for the aquaculture industry.

    PubMed

    Pinto, Wilson; Rønnestad, Ivar; Dinis, Maria Teresa; Aragão, Cláudia

    2013-01-01

    Expansion of the aquaculture industry is limited by incomplete knowledge on fish larval nutritional requirements. Nevertheless, it is believed that dietary taurine deficiencies may be particularly critical for fish larvae. The reasons include the high taurine levels found during egg and yolk-sac stages of fish, suggesting that taurine may be of pivotal importance for larval development. Moreover, unlike aquaculture feeds, natural preys of fish larvae contain high taurine levels, and dietary taurine supplementation has been shown to increase larval growth in several fish species. This study aimed to further explore the physiological role of taurine during fish development. Firstly, the effect of dietary taurine supplementation was assessed on growth of gilthead sea bream (Sparus aurata) larvae and growth, metamorphosis success and amino acid metabolism of Senegalese sole (Solea senegalensis) larvae. Secondly, the expression of taurine transporter (TauT) was characterised by qPCR in sole larvae and juveniles. Results showed that dietary taurine supplementation did not increase sea bream growth. However, dietary taurine supplementation significantly increased sole larval growth, metamorphosis success and amino acid retention. Metamorphosis was also shown to be an important developmental trigger to promote taurine transport in sole tissues, while evidence for an enterohepatic recycling pathway for taurine was found in sole at least from juvenile stage. Taken together, our studies showed that the dependence of dietary taurine supplementation differs among fish species and that taurine has a vital role during the ontogenetic development of flatfish, an extremely valuable group targeted for aquaculture production. PMID:23392894

  11. Taurine uptake across the human intestinal brush-border membrane is via two transporters: H+-coupled PAT1 (SLC36A1) and Na+- and Cl−-dependent TauT (SLC6A6)

    PubMed Central

    Anderson, Catriona M H; Howard, Alison; Walters, Julian R F; Ganapathy, Vadivel; Thwaites, David T

    2009-01-01

    Taurine is an essential amino acid in some mammals and is conditionally essential in humans. Taurine is an abundant component of meat and fish-based foods and has been used as an oral supplement in the treatment of disorders such as cystic fibrosis and hypertension. The purpose of this investigation was to identity the relative contributions of the solute transporters involved in taurine uptake across the luminal membrane of human enterocytes. Distinct transport characteristics were revealed following expression of the candidate solute transporters in Xenopus laevis oocytes: PAT1 (SLC36A1) is a H+-coupled, pH-dependent, Na+- and Cl−-independent, low-affinity, high-capacity transporter for taurine and β-alanine; TauT (SLC6A6) is a Na+- and Cl−-dependent, high-affinity, low-capacity transporter of taurine and β-alanine; ATB0,+ (SLC6A14) is a Na+- and Cl−-dependent, high-affinity, low-capacity transporter which accepts β-alanine but not taurine. Taurine uptake across the brush-border membrane of human intestinal Caco-2 cell monolayers showed characteristics of both PAT1- and TauT-mediated transport. Under physiological conditions, Cl−-dependent TauT-mediated uptake predominates at low taurine concentrations, whereas at higher concentrations typical of diet, Cl−-independent PAT1-mediated uptake is the major absorptive mechanism. Real-time PCR analysis of human duodenal and ileal biopsy samples demonstrates that PAT1, TauT and ATB0,+ mRNA are expressed in each tissue but to varying degrees. In conclusion, this study is the first to demonstrate both taurine uptake via PAT1 and functional coexpression of PAT1 and TauT at the apical membrane of the human intestinal epithelium. PAT1 may be responsible for bulk taurine uptake during a meal whereas TauT may be important for taurine supply to the intestinal epithelium and for taurine capture between meals. PMID:19074966

  12. Physiological roles of taurine in heart and muscle.

    PubMed

    Schaffer, Stephen W; Jong, Chian Ju; Ramila, K C; Azuma, Junichi

    2010-01-01

    Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an

  13. Ontogenetic taurine biosynthesis ability in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Wang, Xuan; He, Gen; Mai, Kangsen; Xu, Wei; Zhou, Huihui

    2015-07-01

    Taurine (2-aminoethane sulfonic acid) plays important roles in multiple physiological processes including osmoregulation, bile salt conjugation and membrane protection. It is known that taurine biosynthesis varies in different fish species. However, its ontogenetic regulation has not been clear. In the present study, we found that the hepatic concentrations of taurine increased marginally with rainbow trout growth. The mRNA expression, protein levels and enzyme activities of key enzymes involved in taurine biosynthesis, cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD), were analyzed. Our results showed that the mRNA levels and protein abundances of CSD increased dramatically with the development of rainbow trout stages while the enzyme activities showed a slight improvement. However, the expression and activities of CDO decreased with rainbow trout growth. These results provide valuable information on defining the exact supplementation of taurine in diets for different stages of rainbow trout and give new insights into elucidating the regulation of taurine metabolism in rainbow trout. PMID:25773436

  14. Mechanisms of enhanced taurine release under Ca2+ depletion.

    PubMed

    Molchanova, Svetlana M; Oja, Simo S; Saransaari, Pirjo

    2005-10-01

    The sulfur-containing amino acid taurine is an inhibitory neuromodulator in the brain of mammals, as well as a key substance in the regulation of cell volumes. The effect of Ca(2+) on extracellular taurine concentrations is of special interest in the context of the regulatory mechanisms of taurine release. The aim of this study was to characterize the basal release of taurine in Ca(2+)-free medium using in vivo microdialysis of the striatum of anesthetized rats. Perfusion of Ca(2+)-free medium via a microdialysis probe evoked a sustained release of taurine (up to 180 % compared to the basal levels). The Ca(2+) chelator EGTA (1mM) potentiated Ca(2+) depletion-evoked taurine release. The substitution of CaCl(2) by choline chloride did not alter the observed effect. Ca(2+)-free solution did not significantly evoke release of taurine from tissue loaded with the competitive inhibitor of taurine transporter guanidinoethanesulfonate (1mM), suggesting that in Ca(2+) depletion taurine is released by the transporter operating in the outward direction. The volume-sensitive chloride channel blocker diisothiocyanostilbene-2,2'-disulfonate (1mM) did not attenuate the taurine release evoked by Ca(2+) depletion. The non-specific blocker of voltage-sensitive Ca(2+) channels NiCl(2) (0.65 mM) enhanced taurine release in the presence of Ca(2+). CdCl(2) (0.25 mM) had no effect under these conditions. However, both CdCl(2) and NiCl(2) attenuated the effect of Ca(2+)-free medium on the release of taurine. The data obtained imply the involvement of both decreased influx of Ca(2+) and increased non-specific influx of Na(+) through voltage-sensitive calcium channels in the regulation of transporter-mediated taurine release in Ca(2+) depletion. PMID:15982785

  15. Role of Hepatic Drug Transporters in Drug Development.

    PubMed

    Liu, Houfu; Sahi, Jasminder

    2016-07-01

    Hepatic drug transporters can play an important role in pharmacokinetics and the disposition of therapeutic drugs and endogenous substances. Altered function of hepatic drug transporters due to drug-drug interactions (DDIs), genetic polymorphisms, and disease states can often result in a change in systemic and/or tissue exposure and subsequent pharmacological/toxicological effects of their substrates. Regulatory agencies including the US Food and Drug Administration, European Medicines Agency, and Japan Pharmaceuticals and Medical Devices Agency have issued guidance for industry on drug interaction studies, which contain comprehensive recommendations on in vitro and in vivo study tools and cutoff values to evaluate the DDI potential of new molecular entities mediated by hepatic drug transporters. In this report we summarize the latest regulatory and scientific progress of hepatic drug transporters in clinical DDIs, pharmacogenetics, drug-induced liver injury (DILI), as well as methods for predicting transporter-mediated pharmacokinetics and DDIs. PMID:27385168

  16. Taurine and inflammatory diseases.

    PubMed

    Marcinkiewicz, Janusz; Kontny, Ewa

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in humans and plays an important role in several essential biological processes such as bile acid conjugation, maintenance of calcium homeostasis, osmoregulation and membrane stabilization. Moreover, attenuation of apoptosis and its antioxidant activity seem to be crucial for the cytoprotective effects of taurine. Although these properties are not tissue specific, taurine reaches particularly high concentrations in tissues exposed to elevated levels of oxidants (e.g., inflammatory cells). It suggests that taurine may play an important role in inflammation associated with oxidative stress. Indeed, at the site of inflammation, taurine is known to react with and detoxify hypochlorous acid generated by the neutrophil myeloperoxidase (MPO)-halide system. This reaction results in the formation of less toxic taurine chloramine (TauCl). Both haloamines, TauCl and taurine bromamine (TauBr), the product of taurine reaction with hypobromous acid (HOBr), exert antimicrobial and anti-inflammatory properties. In contrast to a well-documented regulatory role of taurine and taurine haloamines (TauCl, TauBr) in acute inflammation, their role in the pathogenesis of inflammatory diseases is not clear. This review summarizes our current knowledge concerning the role of taurine, TauCl and TauBr in the pathogenesis of inflammatory diseases initiated or propagated by MPO-derived oxidants. The aim of this paper is to show links between inflammation, neutrophils, MPO, oxidative stress and taurine. We will discuss the possible contribution of taurine and taurine haloamines to the pathogenesis of inflammatory diseases, especially in the best studied example of rheumatoid arthritis. PMID:22810731

  17. Role of taurine accumulation in keratinocyte hydration.

    PubMed

    Janeke, Guido; Siefken, Wilfried; Carstensen, Stefanie; Springmann, Gunja; Bleck, Oliver; Steinhart, Hans; Höger, Peter; Wittern, Klaus-Peter; Wenck, Horst; Stäb, Franz; Sauermann, Gerhard; Schreiner, Volker; Doering, Thomas

    2003-08-01

    Epidermal keratinocytes are exposed to a low water concentration at the stratum corneum-stratum granulosum interface. When epithelial tissues are osmotically perturbed, cellular protection and cell volume regulation is mediated by accumulation of organic osmolytes such as taurine. Previous studies reported the presence of taurine in the epidermis of several animal species. Therefore, we analyzed human skin for the presence of the taurine transporter (TAUT) and studied the accumulation of taurine as one potential mechanism protecting epidermal keratinocytes from dehydration. According to our results, TAUT is expressed as a 69 kDa protein in human epidermis but not in the dermis. For the epidermis a gradient was evident with maximal levels of TAUT in the outermost granular keratinocyte layer and lower levels in the stratum spinosum. No TAUT was found in the basal layer or in the stratum corneum. Keratinocyte accumulation of taurine was induced by experimental induction of skin dryness via application of silica gel to human skin. Cultured human keratinocytes accumulated taurine in a concentration- and osmolarity-dependent manner. TAUT mRNA levels were increased after exposure of human keratinocytes to hyperosmotic culture medium, indicating osmosensitive TAUT mRNA expression as part of the adaptation of keratinocytes to hyperosmotic stress. Keratinocyte uptake of taurine was inhibited by beta-alanine but not by other osmolytes such as betaine, inositol, or sorbitol. Accumulation of taurine protected cultured human keratinocytes from both osmotically induced and ultraviolet-induced apoptosis. Our data indicate that taurine is an important epidermal osmolyte required to maintain keratinocyte hydration in a dry environment. PMID:12880428

  18. Content and traffic of taurine in hippocampal reactive astrocytes.

    PubMed

    Junyent, Fèlix; De Lemos, Luisa; Utrera, Juana; Paco, Sonia; Aguado, Fernando; Camins, Antoni; Pallàs, Mercè; Romero, Rafael; Auladell, Carme

    2011-02-01

    Taurine is one of the most abundant free amino acids in the mammalian central nervous system, where it is crucial to proper development. Moreover, taurine acts as a neuroprotectant in various diseases; in epilepsy, for example, it has the capacity to reduce or abolish seizures. In the present study, taurine levels has been determine in mice treated with Kainic Acid (KA) and results showed an increase of this amino acid in hippocampus but not in whole brain after 3 and 7 days of KA treatment. This increase occurs when gliosis was observed. Moreover, taurine transporter (TAUT) was found in astrocytes 3 and 7 days after KA treatment, together with an increase in cysteine sulfinic acid decarboxylase (csd) mRNA, that codifies for the rate-limiting enzyme of taurine synthesis, in the hippocampus at the same times after KA treatment. Glial cultures enriched in astrocytes were developed to demonstrate that these cells are responsible for changes in taurine levels after an injury to the brain. The cultures were treated with proinflammatory cytokines to reproduce gliosis. In this experimental model, an increase in the immunoreactivity of GFAP was observed, together with an increase in CSD and taurine levels. Moreover, an alteration in the taurine uptake-release kinetics was detected in glial cells treated with cytokine. All data obtained indicate that astrocytes could play a key role in taurine level changes induced by neuronal damage. More studies are, therefore, needed to clarify the role taurine has in relation to neuronal death and repair. PMID:20082296

  19. Renal cortex taurine content regulates renal adaptive response to altered dietary intake of sulfur amino acids.

    PubMed Central

    Chesney, R W; Gusowski, N; Dabbagh, S

    1985-01-01

    Rats fed a reduced sulfur amino acid diet (LTD) or a high-taurine diet (HTD) demonstrate a renal adaptive response. The LTD results in hypotaurinuria and enhanced brush border membrane vesicle (BBMV) accumulation of taurine. The HTD causes hypertaurinuria and reduced BBMV uptake. This adaptation may relate to changes in plasma or renal cortex taurine concentration. Rats were fed a normal-taurine diet (NTD), LTD, or HTD for 14 d or they underwent: (a) 3% beta-alanine for the last 8 d of each diet; (b) 3 d of fasting; or (c) a combination of 3% beta-alanine added for 8 d and 3 d of fasting. Each maneuver lowered the cortex taurine concentration, but did not significantly lower plasma taurine values compared with controls. Increased BBMV taurine uptake occurred after each manipulation. Feeding 3% glycine did not alter the plasma, renal cortex, or urinary taurine concentrations, or BBMV uptake of taurine. Feeding 3% methionine raised plasma and urinary taurine excretion but renal tissue taurine was unchanged, as was initial BBMV uptake. Hence, nonsulfur-containing alpha-amino acids did not change beta-amino acid transport. The increase in BBMV uptake correlates with the decline in renal cortex and plasma taurine content. However, since 3% methionine changed plasma taurine without altering BBMV uptake, it is more likely that the change in BBMV uptake and the adaptive response expressed at the brush border surface relate to changes in renal cortex taurine concentrations. Finally, despite changes in urine and renal cortex taurine content, brain taurine values were unchanged, which suggests that this renal adaptive response maintains stable taurine concentrations where taurine serves as a neuromodulator. PMID:3935668

  20. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    PubMed

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. PMID:26710098

  1. Characteristics of basal taurine release in the rat striatum measured by microdialysis.

    PubMed

    Molchanova, S; Oja, S S; Saransaari, P

    2004-12-01

    Taurine is a sulfur-containing amino acid thought to be an osmoregulator, neurotransmitter or neuromodulator in the brain. Our objective was to establish how much taurine is released in the striatum and examine the mechanisms controlling extracellular taurine concentrations under resting conditions. The experiments were made on rats by microdialysis in vivo. Changes in taurine were compared with those in glutamate, glycine and the non-neuroactive amino acid threonine. Using the zero net flux approach we showed the extracellular concentration of taurine to be 25.2 +/- 5.1 muM. Glutamate was increased by tetrodotoxin and decreased by Ca2+ omission, glycine and threonine were not affected and both treatments increased extracellular taurine. The basal taurine release was increased by the taurine transport inhibitor guanidinoethanesulfonate and reduced by the anion channel blocker 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid. PMID:15549491

  2. Taurine: new implications for an old amino acid.

    PubMed

    Schuller-Levis, Georgia B; Park, Eunkyue

    2003-09-26

    Taurine is a semi-essential amino acid and is not incorporated into proteins. In mammalian tissues, taurine is ubiquitous and is the most abundant free amino acid in the heart, retina, skeletal muscle, brain, and leukocytes. In fact, taurine reaches up to 50 mM concentration in leukocytes. Taurine has been shown to be tissue-protective in many models of oxidant-induced injury. One possibility is that taurine reacts with hypochlorous acid, produced by the myeloperoxidase pathway, to produce the more stable but less toxic taurine chloramine (Tau-Cl). However, data from several laboratories demonstrate that Tau-Cl is a powerful regulator of inflammation. Specifically, Tau-Cl has been shown to down-regulate the production of pro-inflammatory mediators in both rodent and human leukocytes. Taurolidine, a derivative of taurine, is commonly used in Europe as an adjunctive therapy for various infections as well as for tumor therapy. Recent molecular studies on the function of taurine provide evidence that taurine is a constituent of biologic macromolecules. Specifically, two novel taurine-containing modified uridines have been found in both human and bovine mitochondria. Studies investigating the mechanism of action of Tau-Cl have shown that it inhibits the activation of NF-kappaB, a potent signal transducer for inflammatory cytokines, by oxidation of IkappaB-alpha at Met45. Key enzymes for taurine biosynthesis have recently been cloned. Cysteine sulfinic acid decarboxylase, a rate-limiting enzyme for taurine biosynthesis, has been cloned and sequenced in the mouse, rat and human. Another key enzyme for cysteine metabolism, cysteine dioxygenase (CDO), has also been cloned from rat liver. CDO has a critical role in determining the flux of cysteine between cysteine catabolism/taurine synthesis and glutathione synthesis. Taurine transporter knockout mice show reduced taurine, reduced fertility, and loss of vision due to severe apoptotic retinal degeneration. Apoptosis induced

  3. Role of antioxidant activity of taurine in diabetes.

    PubMed

    Schaffer, Stephen W; Azuma, Junichi; Mozaffari, Mahmood

    2009-02-01

    The unifying hypothesis of diabetes maintains that reactive oxygen species (ROS) generated in the mitochondria of glucose-treated cells promote reactions leading to the development of diabetic complications. Although the unifying hypothesis attributes the generation of oxidants solely to impaired glucose and fatty acid metabolism, diabetes is also associated with a decline in the levels of the endogenous antioxidant taurine in a number of tissues, raising the possibility that changes in taurine status might also contribute to the severity of oxidant-mediated damage. There is overwhelming evidence that taurine blocks toxicity caused by oxidative stress, but the mechanism underlying the antioxidant activity remains unclear. One established antioxidant action of taurine is the detoxification of hypochlorous acid. However, not all of the antioxidant actions of taurine are related to hypochlorous acid because they are detected in isolated cell systems lacking neutrophils. There are a few studies showing that taurine either modulates the antioxidant defenses or blocks the actions of the oxidants, but other studies oppose this interpretation. Although taurine is incapable of directly scavenging the classic ROS, such as superoxide anion, hydroxyl radical, and hydrogen peroxide, there are numerous studies suggesting that it is an effective inhibitor of ROS generation. The present review introduces a novel antioxidant hypothesis, which takes into consideration the presence of taurine-conjugated tRNAs in the mitochondria. Because tRNA conjugation is required for normal translation of mitochondrial-encoded proteins, taurine deficiency reduces the expression of these respiratory chain components. As a result, flux through the electron transport chain decreases. The dysfunctional respiratory chain accumulates electron donors, which divert electrons from the respiratory chain to oxygen, forming superoxide anion in the process. Restoration of taurine levels increases the levels of

  4. Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis.

    PubMed

    Burt, Howard J; Riedmaier, Arian Emami; Harwood, Matthew D; Crewe, H Kim; Gill, Katherine L; Neuhoff, Sibylle

    2016-10-01

    This study aimed to derive quantitative abundance values for key hepatic transporters suitable for in vitro-in vivo extrapolation within a physiologically based pharmacokinetic modeling framework. A meta-analysis was performed whereby data on abundance measurements, sample preparation methods, and donor demography were collated from the literature. To define values for a healthy Caucasian population, a subdatabase was created whereby exclusion criteria were applied to remove samples from non-Caucasian individuals, those with underlying disease, or those with subcellular fractions other than crude membrane. Where a clinically relevant active genotype was known, only samples from individuals with an extensive transporter phenotype were included. Authors were contacted directly when additional information was required. After removing duplicated samples, the weighted mean, geometric mean, standard deviation, coefficient of variation, and between-study homogeneity of transporter abundances were determined. From the complete database containing 24 transporters, suitable abundance data were available for 11 hepatic transporters from nine studies after exclusion criteria were applied. Organic anion transporting polypeptides OATP1B1 and OATP1B3 showed the highest population abundance in healthy adult Caucasians. For several transporters, the variability in abundance was reduced significantly once the exclusion criteria were applied. The highest variability was observed for OATP1B3 > OATP1B1 > multidrug resistance protein 2 > multidrug resistance gene 1. No relationship was found between transporter expression and donor age. To our knowledge, this study provides the first in-depth analysis of current quantitative abundance data for a wide range of hepatic transporters, with the aim of using these data for in vitro-in vivo extrapolation, and highlights the significance of investigating the background of tissue(s) used in quantitative transporter proteomic studies. Similar

  5. Effect of sulfide, osmotic, and thermal stresses on taurine transporter mRNA levels in the gills of the hydrothermal vent-specific mussel Bathymodiolus septemdierum.

    PubMed

    Nakamura-Kusakabe, Ikumi; Nagasaki, Toshihiro; Kinjo, Azusa; Sassa, Mieko; Koito, Tomoko; Okamura, Kei; Yamagami, Shosei; Yamanaka, Toshiro; Tsuchida, Shinji; Inoue, Koji

    2016-01-01

    Hydrothermal vent environmental conditions are characterized by high sulfide concentrations, fluctuating osmolality, and irregular temperature elevations caused by vent effluents. These parameters represent potential stressors for organisms that inhabit the area around hydrothermal vents. Here, we aimed to obtain a better understanding of the adaptation mechanisms of marine species to hydrothermal vent environments. Specifically, we examined the effect of sulfide, osmolality, and thermal stress on the expression of taurine transporter (TAUT) mRNA in the gill of the deep-sea mussel Bathymodiolus septemdierum, which is a dominant species around hydrothermal vent sites. We analyzed TAUT mRNA levels by quantitative real-time polymerase chain reaction (PCR) in the gill of mussels exposed to sulfide (0.1 or 1mg/L Na2S·9H2O), hyper- (115% seawater) and hypo- (97.5%, 95.5%, and 85% seawater) osmotic conditions, and thermal stresses (12°C and 20°C) for 24 and 48h. The results showed that mussels exposed to relatively low levels of sulfide (0.1mg/L) and moderate heat stress (12°C) exhibited higher TAUT mRNA levels than the control. Although hyper- and hypo-osmotic stress did not significantly change TAUT mRNA levels, slight induction was observed in mussels exposed to low osmolality. Our results indicate that TAUT is involved in the coping mechanism of mussels to various hydrothermal vent stresses. PMID:26431911

  6. Taurine and the renal system

    PubMed Central

    2010-01-01

    Taurine participates in a number of different physiologic and biologic processes in the kidney, often reflected by urinary excretion patterns. The kidney is key to aspects of taurine body pool size and homeostasis. This review will examine the renal-taurine interactions relative to ion reabsorption; renal blood flow and renal vascular endothelial function; antioxidant properties, especially in the glomerulus; and the role of taurine in ischemia and reperfusion injury. In addition, taurine plays a role in the renal cell cycle and apoptosis, and functions as an osmolyte during the stress response. The role of the kidney in adaptation to variations in dietary taurine intake and the regulation of taurine body pool size are described. Finally, the protective function of taurine against several kidney diseases is reviewed. PMID:20804616

  7. Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

    SciTech Connect

    Das, Joydeep; Vasan, Vandana; Sil, Parames C.

    2012-01-15

    Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ► Taurine controls blood glucose via protection of pancreatic β cells in diabetic rat. ► Taurine controls blood glucose via increasing the insulin level in diabetic rat. ► Taurine improves cardiac AKT/GLUT4 signaling

  8. Hepatic transport of bile acid and effect of conjugation.

    PubMed

    Kitani, K

    1995-06-01

    Biliary transport of bile salts was investigated by measuring: 1) biliary transport maxima values (Tm) for different conjugated bile salts; and 2) biliary excretion of unconjugated bile salts relative to their conjugates under the continuous i.v. infusion of various unconjugated bile salts. The order of Tm values found in the rat of both sexes was tauro (and glyco) ursodeoxycholate (TUDC, GUDC), tauro alpha- and beta-muricholate (T alpha-MC, T beta-MC) > taurocholate(TC) > taurochenodeoxycholate (TCDC), while in female hamsters it was TC > TCDC > TUDC. The differences in the Tm order between rats and hamsters cast doubt on the currently proposed view that the apparent Tm values of bile salts are primarily determined by their physical-chemical properties (detergent property in particular). The biliary excretion of unconjugated bile salts was most efficient with ursocholate (UC) and alpha-MC followed by beta-MC, with UDC (and probably 7 ketolithocholate) being the least efficient for excretion. Thus, while for some bile salts such as cholate and UC, the amidation is not a prerequisite to their efficient excretion, for other bile salts such as UDC, the amidation is an excellent mechanism for facilitating the biliary excretion. In an attempt to explain the above order for the efficacy of the biliary excretion of unconjugated bile salts on the basis of their physical-chemical properties, we must remember that unlike rats, the biliary excretion of dehydrocholate and cholate in dogs is more limited than their respective taurine conjugates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8541581

  9. The potential protective effects of taurine on coronary heart disease.

    PubMed

    Wójcik, Oktawia P; Koenig, Karen L; Zeleniuch-Jacquotte, Anne; Costa, Max; Chen, Yu

    2010-01-01

    In humans, taurine (2-aminoethanesulfonic acid) is mainly obtained from diet. Despite the fact that the health effects of taurine are largely unknown, taurine has become a popular supplement and ingredient in energy drinks in recent years. Evidence from mechanistic and animal studies has shown that the main biological actions of taurine include its ability to conjugate bile acids, regulate blood pressure (BP), and act as a potent antioxidant and anti-inflammatory agent. These actions suggest that high levels of taurine may be protective against coronary heart disease (CHD). However, data from epidemiologic and intervention studies in humans are limited. We review what is known about taurine's metabolism, its transportation in the body, its food sources, and evidence of its effect on cardiovascular health from in vitro, animal, and epidemiologic studies. We also discuss shortcomings of the human studies that need to be addressed in the future. The identification of taurine as a preventive factor for CHD may be of great public health importance. PMID:19592001

  10. TonEBP modulates the protective effect of taurine in ischemia-induced cytotoxicity in cardiomyocytes

    PubMed Central

    Yang, Y J; Han, Y Y; Chen, K; Zhang, Y; Liu, X; Li, S; Wang, K Q; Ge, J B; Liu, W; Zuo, J

    2015-01-01

    Taurine, which is found at high concentration in the heart, exerts several protective actions on myocardium. Physically, the high level of taurine in heart is maintained by a taurine transporter (TauT), the expression of which is suppressed under ischemic insult. Although taurine supplementation upregulates TauT expression, elevates the intracellular taurine content and ameliorates the ischemic injury of cardiomyocytes (CMs), little is known about the regulatory mechanisms of taurine governing TauT expression under ischemia. In this study, we describe the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway involved in the taurine-regulated TauT expression in ischemic CMs. Taurine inhibited the ubiquitin-dependent proteasomal degradation of TonEBP, promoted the translocation of TonEBP into the nucleus, enhanced TauT promoter activity and finally upregulated TauT expression in CMs. In addition, we observed that TonEBP had an anti-apoptotic and anti-oxidative role in CMs under ischemia. Moreover, the protective effects of taurine on myocardial ischemia were TonEBP dependent. Collectively, our findings suggest that TonEBP is a core molecule in the protective mechanism of taurine in CMs under ischemic insult. PMID:26673669

  11. TonEBP modulates the protective effect of taurine in ischemia-induced cytotoxicity in cardiomyocytes.

    PubMed

    Yang, Y J; Han, Y Y; Chen, K; Zhang, Y; Liu, X; Li, S; Wang, K Q; Ge, J B; Liu, W; Zuo, J

    2015-01-01

    Taurine, which is found at high concentration in the heart, exerts several protective actions on myocardium. Physically, the high level of taurine in heart is maintained by a taurine transporter (TauT), the expression of which is suppressed under ischemic insult. Although taurine supplementation upregulates TauT expression, elevates the intracellular taurine content and ameliorates the ischemic injury of cardiomyocytes (CMs), little is known about the regulatory mechanisms of taurine governing TauT expression under ischemia. In this study, we describe the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway involved in the taurine-regulated TauT expression in ischemic CMs. Taurine inhibited the ubiquitin-dependent proteasomal degradation of TonEBP, promoted the translocation of TonEBP into the nucleus, enhanced TauT promoter activity and finally upregulated TauT expression in CMs. In addition, we observed that TonEBP had an anti-apoptotic and anti-oxidative role in CMs under ischemia. Moreover, the protective effects of taurine on myocardial ischemia were TonEBP dependent. Collectively, our findings suggest that TonEBP is a core molecule in the protective mechanism of taurine in CMs under ischemic insult. PMID:26673669

  12. Hepatic microsomal drug oxidation and electron transport in newborn infants.

    PubMed

    Aranda, J V; MacLeod, S M; Renton, K W; Eade, N R

    1974-10-01

    Many drugs require oxidative metabolism for termination of action and/or for elimination from the body. Many oxidative reactions are catalyzed by hepatic microsomal enzymes. The activities of various drug-metabolizing enzymes, namely, NADPH cytochrome c reductase, NADPH oxidase, aminopyrine-N-demethylase, and analine P-hydroxylase, and the content of cytochrome P-450, were measured in hepatic microsomes obtained from seven newborn infants and four adult patients. The results in the newborn infant show increasing activities of these enzymes (except aminopyrine-N-demethylase) related to advancing age. Good correlation between three components of the hepatic microsomal mixed function oxidase system and aniline p-hydroxylase was established, whereas only NADPH oxidation correlated with aminopyrine N-demethylation. The rate of substrate or drug oxidation and the activities of the components of the microsomal electron transport pathway were lower than comparable values in the adult. The data demonstrate a possible biochemical basis for the transient deficiency in drug metabolism seen in newborn infants. PMID:4155438

  13. Hepatic mitochondrial glutathione: transport and role in disease and toxicity

    SciTech Connect

    Fernandez-Checa, Jose C. . E-mail: checa229@yahoo.com; Kaplowitz, Neil . E-mail: kaplowitz@hsc.usc.edu

    2005-05-01

    Synthesized in the cytosol of cells, a fraction of cytosolic glutathione (GSH) is then transported into the mitochondrial matrix where it reaches a high concentration and plays a critical role in defending mitochondria against oxidants and electrophiles. Evidence mainly from kidney and liver mitochondria indicated that the dicarboxylate and the 2-oxoglutarate carriers contribute to the transport of GSH across the mitochondrial inner membrane. However, differential features between kidney and liver mitochondrial GSH (mGSH) transport seem to suggest the existence of additional carriers the identity of which remains to be established. One of the characteristic features of the hepatic mitochondrial transport of GSH is its regulation by membrane fluidity. Conditions leading to increased cholesterol deposition in the mitochondrial inner membrane such as in alcohol-induced liver injury decrease membrane fluidity and impair the mitochondrial transport of GSH. Depletion of mitochondrial GSH by alcohol is believed to contribute to the sensitization of the liver to alcohol-induced injury through tumor necrosis factor (TNF)-mediated hepatocellular death. Through control of mitochondrial electron transport chain-generated oxidants, mitochondrial GSH modulates cell death and hence its regulation may be a key target to influence disease progression and drug-induced cell death.

  14. [Progress in research on function and mechanism of cardiac vascular system of taurine].

    PubMed

    Hua, Hao-ming; Ito, Takashi; Qiu, Zhi-gang; Azuma, Junichi

    2005-05-01

    The function for cardiac vascular system of taurine is extensive, and the mechanism is complicated. Taurine protects the cells from the cell injury caused by ischemia etc. Through repressing apoptosis, prevents endothelial dysfunction caused by hyperglycemia, hypercholesterolemia, smoking and homocysteine; suppresses the proliferation and calcification in vascular smooth muscle cells, promotes metabolization and excretion of cholesterol in the animal models of hyperlipemia, and confers the resistance to an oxidant, hypochlorous acid, produced by neutrophil on cells, and taurine chrolamine to inhibit activation of NF-kappaB, which might be associated with anti-atherosclerotic effect. Taurine mainly acts inside the cell. However, taurine transport system becomes aberrant in pathological myocardial and vascular tissue. In addition, taurine improves cardiovascular function in fructose-induced hypertension and an iron-overload murine animal models. PMID:16075725

  15. The effect of taurine, a novel biochemical modulator, on the antitumor activity of doxorubicin.

    PubMed

    Sadzuka, Yasuyuki; Matsuura, Makoto; Sonobe, Takashi

    2009-09-01

    Taurine is contained in seafood and has been studied extensively on life-style related diseases. Theanine increased the effects of the doxorubicin (DOX) as an antitumor agent in some tumors and enhanced the DOX level in tumor cells. It is expected that the advanced effect of food uptake in cancer chemotherapy may be effective from the viewpoint of quality of life (QOL) improvement, although this approach has not been investigated in detail. In this study, the effect of taurine as a functional amino acid was examined. Taurine did not change the DOX influx into M5076 cells, whereas it significantly inhibited DOX efflux, which maintained the DOX level in tumor cells. Furthermore, experiments with taurine decreased tumor weight by 40%, compared to the DOX-alone group and significantly increased its antitumor effect. Moreover, as taurine did not increase DOX concentration in normal tissue, it is suggested that it increased the antitumor effect without enhancing DOX-induced adverse effects. DOX efflux is inhibited by beta-alanine as a taurine transporter inhibitor, therefore, enhancement of the DOX level by taurine was suggested to act via taurine transport. Namely, it was clarified that taurine was useful as a modulator to enhance the therapeutic index of cancer patients and improve QOL. PMID:19721236

  16. Hepatitis

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  17. Hyperinsulinemia Enhances Hepatic Expression of the Fatty Acid Transporter Cd36 and Provokes Hepatosteatosis and Hepatic Insulin Resistance*

    PubMed Central

    Steneberg, Pär; Sykaras, Alexandros G.; Backlund, Fredrik; Straseviciene, Jurate; Söderström, Ingegerd; Edlund, Helena

    2015-01-01

    Hepatosteatosis is associated with the development of both hepatic insulin resistance and Type 2 diabetes. Hepatic expression of Cd36, a fatty acid transporter, is enhanced in obese and diabetic murine models and human nonalcoholic fatty liver disease, and thus it correlates with hyperinsulinemia, steatosis, and insulin resistance. Here, we have explored the effect of hyperinsulinemia on hepatic Cd36 expression, development of hepatosteatosis, insulin resistance, and dysglycemia. A 3-week sucrose-enriched diet was sufficient to provoke hyperinsulinemia, hepatosteatosis, hepatic insulin resistance, and dysglycemia in CBA/J mice. The development of hepatic steatosis and insulin resistance in CBA/J mice on a sucrose-enriched diet was paralleled by increased hepatic expression of the transcription factor Pparγ and its target gene Cd36 whereas that of genes implicated in lipogenesis, fatty acid oxidation, and VLDL secretion was unaltered. Additionally, we demonstrate that insulin, in a Pparγ-dependent manner, is sufficient to directly increase Cd36 expression in perfused livers and isolated hepatocytes. Mouse strains that display low insulin levels, i.e. C57BL6/J, and/or lack hepatic Pparγ, i.e. C3H/HeN, do not develop hepatic steatosis, insulin resistance, or dysglycemia on a sucrose-enriched diet, suggesting that elevated insulin levels, via enhanced CD36 expression, provoke fatty liver development that in turn leads to hepatic insulin resistance and dysglycemia. Thus, our data provide evidence for a direct role for hyperinsulinemia in stimulating hepatic Cd36 expression and thus the development of hepatosteatosis, hepatic insulin resistance, and dysglycemia. PMID:26085100

  18. Tissue Depletion of Taurine Accelerates Skeletal Muscle Senescence and Leads to Early Death in Mice

    PubMed Central

    Ito, Takashi; Yoshikawa, Natsumi; Inui, Takaaki; Miyazaki, Natsuko; Schaffer, Stephen W.; Azuma, Junichi

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is found in milimolar concentrations in mammalian tissues. One of its main functions is osmoregulation; however, it also exhibits cytoprotective activity by diminishing injury caused by stress and disease. Taurine depletion is associated with several defects, many of which are found in the aging animal, suggesting that taurine might exert anti-aging actions. Therefore, in the present study, we examined the hypothesis that taurine depletion accelerates aging by reducing longevity and accelerating aging-associated tissue damage. Tissue taurine depletion in taurine transporter knockout (TauTKO) mouse was found to shorten lifespan and accelerate skeletal muscle histological and functional defects, including an increase in central nuclei containing myotubes, a reduction in mitochondrial complex 1 activity and an induction in an aging biomarker, Cyclin-dependent kinase 4 inhibitor A (p16INK4a). Tissue taurine depletion also enhances unfolded protein response (UPR), which may be associated with an improvement in protein folding by taurine. Our data reveal that tissue taurine depletion affects longevity and cellular senescence; an effect possibly linked to a disturbance in protein folding. PMID:25229346

  19. Taurine in neonatal nutrition - revisited

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Taurine (2-aminoethanesulfonic acid) was isolated from ox (Bos Taurus) bile in 1827 but, until the mid to late 1970, it was thought to be merely a by-product of sulfur amino and metabolism. In 1975, it was noted that taurine deficiency in cats was associated with retinal degeneration which was reve...

  20. Intracellular transport and egress of hepatitis B virus.

    PubMed

    Blondot, Marie-Lise; Bruss, Volker; Kann, Michael

    2016-04-01

    Hepatitis B virus (HBV) replicates its genomic information in the nucleus via transcription and therefore has to deliver its partially double stranded DNA genome into the nucleus. Like other viruses with a nuclear replication phase, HBV genomes are transported inside the viral capsids first through the cytoplasm towards the nuclear envelope. Following the arrival at the nuclear pore, the capsids are transported through, using classical cellular nuclear import pathways. The arrest of nuclear import at the nucleoplasmic side of the nuclear pore is unique, however, and is where the capsids efficiently disassemble leading to genome release. In the latter phase of the infection, newly formed nucleocapsids in the cytosol have to move to budding sites at intracellular membranes carrying the three viral envelope proteins. Capsids containing single stranded nucleic acid are not enveloped, in contrast to empty and double stranded DNA containing capsids. A small linear domain in the large envelope protein and two areas on the capsid surface have been mapped, where point mutations strongly block nucleocapsid envelopment. It is possible that these domains are involved in the envelope - with capsid interactions driving the budding process. Like other enveloped viruses, HBV also uses the cellular endosomal sorting complexes required for transport (ESCRT) machinery for catalyzing budding through the membrane and away from the cytosol. PMID:27084037

  1. Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses.

    PubMed

    Nagai, Katsuhito; Fukuno, Shuhei; Oda, Ayano; Konishi, Hiroki

    2016-01-01

    The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppressive effects of taurine in terms of alterations in oxidative stress and apoptotic responses. DOX-induced body weight loss was completely suppressed by taurine treatment. Elevations in the serum activity levels of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase by DOX were also dose-dependently attenuated by a concurrent treatment with taurine. Superoxide dismutase activity and reduced glutathione content in the liver were decreased following the administration of DOX, whereas these changes were suppressed when 10 mg/kg taurine was given in combination with DOX. Taurine attenuated the increased expression of mRNAs for Fas and Bax after DOX exposure. Furthermore, the formation of cleaved caspase-3 protein in the group given DOX with taurine was lower than that in the group treated with DOX alone. Our results suggest that taurine can protect against DOX-induced acute hepatic damage, the underlying mechanism of which is attributable to the suppression of oxidative stress and apoptotic responses. PMID:26426519

  2. Regulation of hepatic bile acid transporters Ntcp and Bsep expression.

    PubMed

    Cheng, Xingguo; Buckley, David; Klaassen, Curtis D

    2007-12-01

    Sodium-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) are two key transporters for hepatic bile acid uptake and excretion. Alterations in Ntcp and Bsep expression have been reported in pathophysiological conditions. In the present study, the effects of age, gender, and various chemicals on the regulation of these two transporters were characterized in mice. Ntcp and Bsep mRNA levels in mouse liver were low in the fetus, but increased to its highest expression at parturition. After birth, mouse Ntcp and Bsep mRNA decreased by more than 50%, and then gradually increased to adult levels by day 30. Expression of mouse Ntcp mRNA and protein exhibit higher levels in female than male livers. No gender difference exists in BSEP/Bsep expression in human and mouse livers. Hormone replacements conducted in gonadectomized, hypophysectomized, and lit/lit mice indicate that female-predominant Ntcp expression in mouse liver is due to the inhibitory effect of male-pattern GH secretion, but not sex hormones. Ntcp and Bsep expression are in general resistant to induction by a large battery of microsomal enzyme inducers. Administration of cholestyramine increased Ntcp, whereas chenodeoxycholic acid (CDCA) increased Bsep mRNA expression. In conclusion, mouse Ntcp and Bsep are regulated by age, gender, cholestyramine, and bile acid, but resistant to induction by most microsomal enzyme inducers. PMID:17897632

  3. The effect of taurine on the cholesterol metabolism in rats fed diets supplemented with cholestyramine or high amounts of bile acid.

    PubMed

    Nishimura, Naomichi; Umeda, Chie; Oda, Hiroaki; Yokogoshi, Hidehiko

    2003-02-01

    The effects of taurine on serum cholesterol levels and hepatic cholesterol 7alpha-hydroxylase activity (CYP7A1) were studied in rats fed cholestyramine or high amounts of sodium cholate in order to alter the intestinal pool of bile acids. Rats were fed a diet supplemented with 1% cholesterol and 0.25% sodium cholate (high cholesterol, control; C), and C supplemented with 4% cholestyramine (CH) or 0.75% sodium cholate (BA) for 14 d. Taurine groups were fed the diet supplemented with 3% taurine (CT, CHT and BAT). Compared to rats fed C and BA diets, serum cholesterol levels were significantly reduced in rats fed CT and BAT diets, but a significant reduction of serum cholesterol by taurine feeding was not observed in the CHT group as compared to the CH group. An increase in hepatic CYP7A1 activity due to taurine intake was observed in the CT and BAT groups. However, the simultaneous administration of cholestyramine and taurine (CHT group) did not increase hepatic CYP7A1 activity compared the intake of cholestyramine only (CH group). A significant increase in fecal bile acid excretion due to taurine intake was found only in rats fed the CT diet. In conclusion, it is suggested that taurine facilitates hepatic CYP7A1 activity regardless of the enlarged intestinal pool of bile acids due to increased intake of exogenous bile acid, and then reduces the serum cholesterol concentration. PMID:12882392

  4. Mechanism for modulation of gating of connexin26-containing channels by taurine

    PubMed Central

    Kieken, Fabien; Tao, Liang; Sorgen, Paul L.; Harris, Andrew L.

    2011-01-01

    The mechanisms of action of endogenous modulatory ligands of connexin channels are largely unknown. Previous work showed that protonated aminosulfonates (AS), notably taurine, directly and reversibly inhibit homomeric and heteromeric channels that contain Cx26, a widely distributed connexin, but not homomeric Cx32 channels. The present study investigated the molecular mechanisms of connexin channel modulation by taurine, using hemichannels and junctional channels composed of Cx26 (homomeric) and Cx26/Cx32 (heteromeric). The addition of a 28–amino acid “tag” to the carboxyl-terminal domain (CT) of Cx26 (Cx26T) eliminated taurine sensitivity of homomeric and heteromeric hemichannels in cells and liposomes. Cleavage of all but four residues of the tag (Cx26Tc) resulted in taurine-induced pore narrowing in homomeric hemichannels, and restored taurine inhibition of heteromeric hemichannels (Cx26Tc/Cx32). Taurine actions on junctional channels were fully consistent with those on hemichannels. Taurine-induced inhibition of Cx26/Cx32T and nontagged Cx26 junctional channels was blocked by extracellular HEPES, a blocker of the taurine transporter, confirming that the taurine-sensitive site of Cx26 is cytoplasmic. Nuclear magnetic resonance of peptides corresponding to Cx26 cytoplasmic domains showed that taurine binds to the cytoplasmic loop (CL) and not the CT, and that the CT and CL directly interact. ELISA showed that taurine disrupts a pH-dependent interaction between the CT and the CT-proximal half of the CL. These studies reveal that AS disrupt a pH-driven cytoplasmic interdomain interaction in Cx26-containing channels, causing closure, and that the Cx26CT has a modulatory role in Cx26 function. PMID:21844220

  5. Role of taurine in the vasculature: an overview of experimental and human studies

    PubMed Central

    Abebe, Worku; Mozaffari, Mahmood S

    2011-01-01

    Taurine is a sulfur-containing amino acid-like endogenous compound found in substantial amounts in mammalian tissues. It exerts a diverse array of biological effects, including cardiovascular regulation, antioxidation, modulation of ion transport, membrane stabilization, osmoregulation, modulation of neurotransmission, bile acid conjugation, hypolipidemia, antiplatelet activity and modulation of fetal development. This brief review summarizes the role of taurine in the vasculature and modulation of blood pressure, based on experimental and human studies. Oral supplementation of taurine induces antihypertensive effects in various animal models of hypertension. These effects of taurine have been shown to be both centrally and peripherally mediated. Consistent with this, taurine produces endothelium-dependent and independent relaxant effects in isolated vascular tissue preparations. Oral administration of taurine also ameliorates impairment of vascular reactivity, intimal thickening, arteriosclerosis, endothelial apoptosis, oxidative stress and inflammation, associated primarily with diabetes and, to a lesser extent with obesity, hypertension and nicotine-induced vascular adverse events. In rat aortic vascular smooth muscle cells (VSMCs), taurine acts as an antiproliferative and antioxidant agent. In endothelial cells, taurine inhibits apoptosis, inflammation, oxidative stress and cell death while increasing NO generation. Oral taurine in hypertensive human patients alleviates the symptoms of hypertension and also reverses arterial stiffness and brachial artery reactivity in type 1 diabetic patients. However, despite these favorable findings, there is a need to further establish certain aspects of the reported results and also consider addressing unresolved related issues. In addition, the molecular mechanism (s) involved in the vascular effects of taurine is largely unknown and requires further investigations. Elucidation of the mechanisms through which taurine

  6. The osmolyte taurine protects against ultraviolet B radiation-induced immunosuppression.

    PubMed

    Rockel, Nicole; Esser, Charlotte; Grether-Beck, Susanne; Warskulat, Ulrich; Flögel, Ulrich; Schwarz, Agatha; Schwarz, Thomas; Yarosh, Daniel; Häussinger, Dieter; Krutmann, Jean

    2007-09-15

    Organic osmolytes, such as taurine, are involved in cell volume homeostasis and cell protection. Epidermal keratinocytes possess an osmolyte strategy, i.e., they take up taurine upon hyperosmotic stress and express the corresponding transporter TAUT. UVB irradiation also triggers taurine uptake and TAUT expression in this cell type. We therefore asked whether taurine plays a role in photoprotection. By using a TAUT-deficient mouse model, lack of taurine in the skin was found to cause a significantly higher sensitivity to UVB-induced immunosuppression. This was not due to an increased generation or decreased repair of UVB-induced DNA photoproducts in the skin of these animals. Instead, decreased skin taurine levels were associated with an increased formation of the soluble immunosuppressive molecule platelet-activating factor (PAF) from the membranes of UVB-irradiated epidermal cells. Blocking PAF activity in taut-deficient mice with a PAF receptor antagonist abrogated their increased sensitivity to UVB-induced immunosuppression. Moreover, taut -/- mice were more sensitive to PAF-mediated immunosuppression than taut +/+ mice. These data suggest that taurine uptake by epidermal cells prevents undue PAF formation, and thereby photoimmunosuppression. Thus, similar to nucleotide excision repair, taurine uptake is critically involved in photoprotection of the skin. PMID:17785795

  7. Protective effects of taurine in traumatic brain injury via mitochondria and cerebral blood flow.

    PubMed

    Wang, Qin; Fan, Weijia; Cai, Ying; Wu, Qiaoli; Mo, Lidong; Huang, Zhenwu; Huang, Huiling

    2016-09-01

    In mammalian tissues, taurine is an important natural component and the most abundant free amino acid in the heart, retina, skeletal muscle, brain, and leukocytes. This study is to examine the taurine's protective effects on neuronal ultrastructure, the function of the mitochondrial respiratory chain complex, and on cerebral blood flow (CBF). The model of traumatic brain injury (TBI) was made for SD rats by a fluid percussion device, with taurine (200 mg/kg) administered by tail intravenous injection once daily for 7 days after TBI. It was found that CBF was improved for both left and right brain at 30 min and 7 days post-injury by taurine. Reaction time was prolonged relative to the TBI-only group. Neuronal damage was prevented by 7 days taurine. Mitochondrial electron transport chain complexes I and II showed greater activity with the taurine group. The improvement by taurine of CBF may alleviate edema and elevation in intracranial pressure. Importantly taurine improved the hypercoagulable state. PMID:27156064

  8. Regulation of hepatic bile acid transporters Ntcp and Bsep expression

    PubMed Central

    Cheng, Xingguo; Buckley, David; Klaassen, Curtis D.

    2009-01-01

    Sodium-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) are two key transporters for hepatic bile acid uptake and excretion. Alterations in Ntcp and Bsep expression have been reported in pathophysiological conditions. In the present study, the effects of age, gender, and various chemicals on the regulation of these two transporters were characterized in mice. Ntcp and Bsep mRNA levels in mouse liver were low in the fetus, but increased to its highest expression at parturition. After birth, mouse Ntcp and Bsep mRNA decreased by more than 50%, and then gradually increased to adult levels by day 30. Expression of mouse Ntcp mRNA and protein exhibit higher levels in female than male livers, which is consistent with the trend of human NTCP mRNA expression between men and women. No gender difference exists in BSEP/Bsep expression in human and mouse livers. Hormone replacements conducted in gonadectomized, hypophysectomized, and lit/lit mice indicate that female-predominant Ntcp expression in mouse liver is due to the inhibitory effect of male-pattern GH secretion, but not sex hormones. Ntcp and Bsep expression are in general resistant to induction by a large battery of microsomal enzyme inducers. Administration of cholestyramine increased Ntcp, whereas chenodeoxycholic acid increased Bsep mRNA expression. In silico analysis indicates that female-predominant mouse and human Ntcp/NTCP expression may be due to GH. In conclusion, mouse Ntcp and Bsep are regulated by age, gender, cholestyramine, and bile acid, but resistant to induction by most microsomal enzyme inducers. PMID:17897632

  9. Dysregulated hepatic expression of glucose transporters in chronic disease: contribution of semicarbazide-sensitive amine oxidase to hepatic glucose uptake

    PubMed Central

    Karim, Sumera; Liaskou, Evaggelia; Fear, Janine; Garg, Abhilok; Reynolds, Gary; Claridge, Lee; Adams, David H.; Newsome, Philip N.

    2014-01-01

    Insulin resistance is common in patients with chronic liver disease (CLD). Serum levels of soluble vascular adhesion protein-1 (VAP-1) are also increased in these patients. The amine oxidase activity of VAP-1 stimulates glucose uptake via translocation of transporters to the cell membrane in adipocytes and smooth muscle cells. We aimed to document human hepatocellular expression of glucose transporters (GLUTs) and to determine if VAP-1 activity influences receptor expression and hepatic glucose uptake. Quantitative PCR and immunocytochemistry were used to study human liver tissue and cultured cells. We also used tissue slices from humans and VAP-1-deficient mice to assay glucose uptake and measure hepatocellular responses to stimulation. We report upregulation of GLUT1, -3, -5, -6, -7, -8, -9, -10, -11, -12, and -13 in CLD. VAP-1 expression and enzyme activity increased in disease, and provision of substrate to hepatic VAP-1 drives hepatic glucose uptake. This effect was sensitive to inhibition of VAP-1 and could be recapitulated by H2O2. VAP-1 activity also altered expression and subcellular localization of GLUT2, -4, -9, -10, and -13. Therefore, we show, for the first time, alterations in hepatocellular expression of glucose and fructose transporters in CLD and provide evidence that the semicarbazide-sensitive amine oxidase activity of VAP-1 modifies hepatic glucose homeostasis and may contribute to patterns of GLUT expression in chronic disease. PMID:25342050

  10. Dysregulated hepatic expression of glucose transporters in chronic disease: contribution of semicarbazide-sensitive amine oxidase to hepatic glucose uptake.

    PubMed

    Karim, Sumera; Liaskou, Evaggelia; Fear, Janine; Garg, Abhilok; Reynolds, Gary; Claridge, Lee; Adams, David H; Newsome, Philip N; Lalor, Patricia F

    2014-12-15

    Insulin resistance is common in patients with chronic liver disease (CLD). Serum levels of soluble vascular adhesion protein-1 (VAP-1) are also increased in these patients. The amine oxidase activity of VAP-1 stimulates glucose uptake via translocation of transporters to the cell membrane in adipocytes and smooth muscle cells. We aimed to document human hepatocellular expression of glucose transporters (GLUTs) and to determine if VAP-1 activity influences receptor expression and hepatic glucose uptake. Quantitative PCR and immunocytochemistry were used to study human liver tissue and cultured cells. We also used tissue slices from humans and VAP-1-deficient mice to assay glucose uptake and measure hepatocellular responses to stimulation. We report upregulation of GLUT1, -3, -5, -6, -7, -8, -9, -10, -11, -12, and -13 in CLD. VAP-1 expression and enzyme activity increased in disease, and provision of substrate to hepatic VAP-1 drives hepatic glucose uptake. This effect was sensitive to inhibition of VAP-1 and could be recapitulated by H2O2. VAP-1 activity also altered expression and subcellular localization of GLUT2, -4, -9, -10, and -13. Therefore, we show, for the first time, alterations in hepatocellular expression of glucose and fructose transporters in CLD and provide evidence that the semicarbazide-sensitive amine oxidase activity of VAP-1 modifies hepatic glucose homeostasis and may contribute to patterns of GLUT expression in chronic disease. PMID:25342050

  11. Taurine supplementation improves the utilization of sulfur-containing amino acids in rats continually administrated alcohol.

    PubMed

    Yang, Hui-Ting; Chien, Yi-Wen; Tsen, Jen-Horng; Chang, Ching-Chien; Chang, Jer-Hwa; Huang, Shih-Yi

    2009-02-01

    The main purpose of this study was to evaluate changes in brain sulfur-containing amino acid (SCAA) metabolism to determine whether taurine intervened under continuous alcohol intake. We fed 80 male Sprague-Dawley rats 30% alcohol-containing water for 4 weeks. Eighty animals were divided into two groups (with or without 2 g/kg body weight taurine supplementation), and five were killed every week in each group for monitoring SCAA changes in the brain, liver, kidneys and heart. Results indicated that the plasma alcohol concentration increased from Weeks 1-4; however, animals with taurine supplementation showed a lower plasma concentration of ethanol in Week 2. As to SCAA concentrations, cysteine and taurine were both lower after a week of alcohol ingestion in the brain and plasma; the same declining trend was shown in the liver in Week 2. In contrast, plasma and hepatic concentrations of homocysteine were elevated in Week 2, and the plasma S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio also decreased in Week 1. Furthermore, the key cofactor of transsulfuration, pyridoxal-5'-phosphate, significantly declined in the plasma after a week of the ethanol intervention, whereas an increase was observed in brain tissue. Under taurine supplementation, some recoveries were shown by delaying taurine depletion to Week 2, increasing the SAM/SAH ratio and elevating plasma and brain levels of vitamin B6 in Week 2. In conclusion, daily consumption of 30% alcohol interfered with SCAA metabolism, thus decreasing taurine's role in neurotransmission. The possible mechanism involved might be that ethanol interrupts the production of cysteine, which is the upstream SCAA of taurine, thus decreasing the homocysteine level. Additionally, taurine supplementation delayed this process. PMID:18547794

  12. Pharmacological characterization of volume-sensitive, taurine permeable anion channels in rat supraoptic glial cells

    PubMed Central

    Brès, Vanessa; Hurbin, Amandine; Duvoid, Anne; Orcel, Hélène; Moos, Françoise C; Rabié, Alain; Hussy, Nicolas

    2000-01-01

    To characterize the volume-sensitive, osmolyte permeable anion channels responsible for the osmodependent release of taurine from supraoptic nucleus (SON) astrocytes, we investigated the pharmacological properties of the [3H]-taurine efflux from acutely isolated SON.Taurine release induced by hypotonic stimulus (250 mosmol l−1) was not antagonized by the taurine transporter blocker guanidinoethyl sulphonate, confirming the lack of implication of the transporter.The osmodependent release of taurine was blocked by a variety of Cl− channel inhibitors with the order of potency: NPPB>niflumic acid>DPC>DIDS>ATP. On the other hand, release of taurine was only weakly affected by other compounds (dideoxyforskolin, 4-bromophenacyl bromide, mibefradil) known to block volume-activated anion channels in other cell preparations, and was completely insensitive to tamoxifen, a broad inhibitor of these channels.Although the molecular identity of volume-sensitive anion channels is not firmly established, a few genes have been postulated as potential candidates to encode such channels. We checked the expression in the SON of three of them, ClC3, phospholemman and VDAC1, and found that the transcripts of these genes are found in SON neurons, but not in astrocytes. Similar observation was previously reported for ClC2.In conclusion, the osmodependent taurine permeable channels of SON astrocytes display a particular pharmacological profile, suggesting the expression of a particular type or subtype of volume-sensitive anion channel, which is likely to be formed by yet unidentified proteins. PMID:10952690

  13. Pharmacological characterization of volume-sensitive, taurine permeable anion channels in rat supraoptic glial cells.

    PubMed

    Brès, V; Hurbin, A; Duvoid, A; Orcel, H; Moos, F C; Rabié, A; Hussy, N

    2000-08-01

    To characterize the volume-sensitive, osmolyte permeable anion channels responsible for the osmodependent release of taurine from supraoptic nucleus (SON) astrocytes, we investigated the pharmacological properties of the [(3)H]-taurine efflux from acutely isolated SON. Taurine release induced by hypotonic stimulus (250 mosmol l(-1)) was not antagonized by the taurine transporter blocker guanidinoethyl sulphonate, confirming the lack of implication of the transporter. The osmodependent release of taurine was blocked by a variety of Cl(-) channel inhibitors with the order of potency: NPPB>niflumic acid>DPC>DIDS>ATP. On the other hand, release of taurine was only weakly affected by other compounds (dideoxyforskolin, 4-bromophenacyl bromide, mibefradil) known to block volume-activated anion channels in other cell preparations, and was completely insensitive to tamoxifen, a broad inhibitor of these channels. Although the molecular identity of volume-sensitive anion channels is not firmly established, a few genes have been postulated as potential candidates to encode such channels. We checked the expression in the SON of three of them, ClC(3), phospholemman and VDAC(1), and found that the transcripts of these genes are found in SON neurons, but not in astrocytes. Similar observation was previously reported for ClC(2). In conclusion, the osmodependent taurine permeable channels of SON astrocytes display a particular pharmacological profile, suggesting the expression of a particular type or subtype of volume-sensitive anion channel, which is likely to be formed by yet unidentified proteins. PMID:10952690

  14. Hepatitis

    MedlinePlus

    ... has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool to ... risk for severe disease. Others A variety of viruses can affect the liver Signs and Symptoms Hepatitis ...

  15. Saturable Hepatic Extraction of Gemcitabine Involves Biphasic Uptake Mediated by Nucleoside Transporters Equilibrative Nucleoside Transporter 1 and 2.

    PubMed

    Shimada, Takuya; Nakanishi, Takeo; Tajima, Hidehiro; Yamazaki, Maiko; Yokono, Rina; Takabayashi, Makiko; Shimada, Tsutomu; Sawamoto, Kazuki; Miyamoto, Ken-Ichi; Kitagawa, Hirohisa; Ohta, Tetsuo; Tamai, Ikumi; Sai, Yoshimichi

    2015-09-01

    Hepatic arterial infusion (HAI) chemotherapy with gemcitabine (GEM) is expected to be more effective and safer method to treat hepatic metastasis of pancreatic cancer compared with intravenous administration, because it affords higher tumor exposure with lower systemic exposure. Thus, a key issue for dose selection is the saturability of hepatic uptake of GEM. Therefore, we investigated GEM uptake in rat and human isolated hepatocytes. Hepatic GEM uptake involved high- and low-affinity saturable components with Km values of micromolar and millimolar order, respectively. The uptake was inhibited concentration dependently by S-(4-nitrobenzyl)-6-thioinosine (NBMPR) and was sodium-ion-independent, suggesting a contribution of equilibrative nucleoside transporters (ENTs). The concentration dependence of uptake in the presence of 0.1 μM NBMPR showed a single low-affinity binding site. Therefore, the high- and low-affinity sites correspond to ENT1 and ENT2, respectively. Our results indicate hepatic extraction of GEM is predominantly mediated by the low-affinity site (hENT2), and at clinically relevant hepatic concentrations of GEM, hENT2-mediated uptake would not be completely saturated. This is critical for HAI, because saturation of hepatic uptake would result in a marked increase of GEM concentration in the peripheral circulation, abrogating the advantage of HAI over intravenous administration in terms of severe adverse events. PMID:26037416

  16. Alteration of human hepatic drug transporter activity and expression by cigarette smoke condensate.

    PubMed

    Sayyed, Katia; Vee, Marc Le; Abdel-Razzak, Ziad; Jouan, Elodie; Stieger, Bruno; Denizot, Claire; Parmentier, Yannick; Fardel, Olivier

    2016-07-01

    Smoking is well-known to impair pharmacokinetics, through inducing expression of drug metabolizing enzymes. In the present study, we demonstrated that cigarette smoke condensate (CSC) also alters activity and expression of hepatic drug transporters, which are now recognized as major actors of hepatobiliary elimination of drugs. CSC thus directly inhibited activities of sinusoidal transporters such as OATP1B1, OATP1B3, OCT1 and NTCP as well as those of canalicular transporters like P-glycoprotein, MRP2, BCRP and MATE1, in hepatic transporters-overexpressing cells. CSC similarly counteracted constitutive OATP, NTCP and OCT1 activities in human highly-differentiated hepatic HepaRG cells. In parallel, CSC induced expression of BCRP at both mRNA and protein level in HepaRG cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B1, OATP2B1, OAT2, NTCP, OCT1 and BSEP, and enhanced that of MRP4. Such changes in transporter gene expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin, a reference activator of the aryl hydrocarbon receptor (AhR) pathway, and were counteracted, for some of them, by siRNA-mediated AhR silencing. This suggests that CSC alters hepatic drug transporter levels via activation of the AhR cascade. Importantly, drug transporter expression regulations as well as some transporter activity inhibitions occurred for a range of CSC concentrations similar to those required for inducing drug metabolizing enzymes and may therefore be hypothesized to be relevant for smokers. Taken together, these data established human hepatic transporters as targets of cigarette smoke, which could contribute to known alteration of pharmacokinetics and some liver adverse effects caused by smoking. PMID:27450509

  17. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

    PubMed

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

    2015-11-15

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (P<0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P<0.01). qBase(+) was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P<0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. PMID:26335259

  18. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

    PubMed Central

    Gentile, Christopher L.; Nivala, Angela M.; Gonzales, Jon C.; Pfaffenbach, Kyle T.; Wang, Dong; Wei, Yuren; Jiang, Hua; Orlicky, David J.; Petersen, Dennis R.; Maclean, Kenneth N.

    2011-01-01

    The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD. PMID:21957160

  19. Taurine concentration in human blood peripheral lymphocytes: major depression and treatment with the antidepressant mirtazapine.

    PubMed

    Lima, Lucimey; Obregón, Francisco; Urbina, Mary; Carreira, Isabel; Baccichet, Edith; Peña, Solisbella

    2003-01-01

    Major depression is a serious disease with various systemic effects, including dysfunction of the immune response. Taurine has been known to be related to certain modifications of the immune system. The aim of this study was to determine the taurine concentration in lymphocytes of patients with major depression and to evaluate the influence of the antidepressant treatment with mirtazapine for six weeks on the levels of taurine. Gamma-aminobutyric acid, aspartate, glutamate and glutamine were also determined. Taurine, aspartate and glutamine levels were increased in the lymphocytes of depressed patients before mirtazapine treatment compared to the control group, and were normalized after treatment. Gamma-aminobutyric acid and glutamate did not differ between patients and controls. There was a significant and positive correlation between the severity of the disorder, measured by the Hamilton Rating Scale, and the concentration of taurine in the lymphocytes of depressed patients before treatment. This correlation was not observed after treatment and neither was there a correlation observed for the other amino acids. The present observations could be an indication of the relevance of taurine as a protective agent in the lymphocytes of patients with severe depression, and could be the result of modifications of taurine transport or efflux processes. PMID:12908614

  20. Transporter-Enzyme Interplay: Deconvoluting Effects of Hepatic Transporters and Enzymes on Drug Disposition Using Static and Dynamic Mechanistic Models.

    PubMed

    Varma, Manthena V; El-Kattan, Ayman F

    2016-07-01

    A large body of evidence suggests hepatic uptake transporters, organic anion-transporting polypeptides (OATPs), are of high clinical relevance in determining the pharmacokinetics of substrate drugs, based on which recent regulatory guidances to industry recommend appropriate assessment of investigational drugs for the potential drug interactions. We recently proposed an extended clearance classification system (ECCS) framework in which the systemic clearance of class 1B and 3B drugs is likely determined by hepatic uptake. The ECCS framework therefore predicts the possibility of drug-drug interactions (DDIs) involving OATPs and the effects of genetic variants of SLCO1B1 early in the discovery and facilitates decision making in the candidate selection and progression. Although OATP-mediated uptake is often the rate-determining process in the hepatic clearance of substrate drugs, metabolic and/or biliary components also contribute to the overall hepatic disposition and, more importantly, to liver exposure. Clinical evidence suggests that alteration in biliary efflux transport or metabolic enzymes associated with genetic polymorphism leads to change in the pharmacodynamic response of statins, for which the pharmacological target resides in the liver. Perpetrator drugs may show inhibitory and/or induction effects on transporters and enzymes simultaneously. It is therefore important to adopt models that frame these multiple processes in a mechanistic sense for quantitative DDI predictions and to deconvolute the effects of individual processes on the plasma and hepatic exposure. In vitro data-informed mechanistic static and physiologically based pharmacokinetic models are proven useful in rationalizing and predicting transporter-mediated DDIs and the complex DDIs involving transporter-enzyme interplay. PMID:27385183

  1. Dysregulation of hepatic zinc transporters in a mouse model of alcoholic liver disease

    PubMed Central

    Sun, Qian; Li, Qiong; Zhong, Wei; Zhang, Jiayang; Sun, Xiuhua; Tan, Xiaobing; Yin, Xinmin; Sun, Xinguo; Zhang, Xiang

    2014-01-01

    Zinc deficiency is a consistent phenomenon observed in patients with alcoholic liver disease, but the mechanisms have not been well defined. The objective of this study was to determine if alcohol alters hepatic zinc transporters in association with reduction of hepatic zinc levels and if oxidative stress mediates the alterations of zinc transporters. C57BL/6 mice were pair-fed with the Lieber-DeCarli control or ethanol diets for 2, 4, or 8 wk. Chronic alcohol exposure reduced hepatic zinc levels, but increased plasma and urine zinc levels, at all time points. Hepatic zinc finger proteins, peroxisome proliferator-activated receptor-α (PPAR-α) and hepatocyte nuclear factor 4α (HNF-4α), were downregulated in ethanol-fed mice. Four hepatic zinc transporter proteins showed significant alterations in ethanol-fed mice compared with the controls. ZIP5 and ZIP14 proteins were downregulated, while ZIP7 and ZnT7 proteins were upregulated, by ethanol exposure at all time points. Immunohistochemical staining demonstrated that chronic ethanol exposure upregulated cytochrome P-450 2E1 and caused 4-hydroxynonenal accumulation in the liver. For the in vitro study, murine FL-83B hepatocytes were treated with 5 μM 4-hydroxynonenal or 100 μM hydrogen peroxide for 72 h. The results from in vitro studies demonstrated that 4-hydroxynonenal treatment altered ZIP5 and ZIP7 protein abundance, and hydrogen peroxide treatment changed ZIP7, ZIP14, and ZnT7 protein abundance. These results suggest that chronic ethanol exposure alters hepatic zinc transporters via oxidative stress, which might account for ethanol-induced hepatic zinc deficiency. PMID:24924749

  2. Osmoregulation of vasopressin secretion via activation of neurohypophysial nerve terminals glycine receptors by glial taurine.

    PubMed

    Hussy, N; Brès, V; Rochette, M; Duvoid, A; Alonso, G; Dayanithi, G; Moos, F C

    2001-09-15

    Osmotic regulation of supraoptic nucleus (SON) neuron activity depends in part on activation of neuronal glycine receptors (GlyRs), most probably by taurine released from adjacent astrocytes. In the neurohypophysis in which the axons of SON neurons terminate, taurine is also concentrated in and osmo-dependently released by pituicytes, the specialized glial cells ensheathing nerve terminals. We now show that taurine release from isolated neurohypophyses is enhanced by hypo-osmotic and decreased by hyper-osmotic stimulation. The high osmosensitivity is shown by the significant increase on only 3.3% reduction in osmolarity. Inhibition of taurine release by 5-nitro-2-(3-phenylpropylamino)benzoic acid, niflumic acid, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid suggests the involvement of volume-sensitive anion channels. On purified neurohypophysial nerve endings, activation of strychnine-sensitive GlyRs by taurine or glycine primarily inhibits the high K(+)-induced rise in [Ca(2+)](i) and subsequent release of vasopressin. Expression of GlyRs in vasopressin and oxytocin terminals is confirmed by immunohistochemistry. Their implication in the osmoregulation of neurohormone secretion was assessed on isolated whole neurohypophyses. A 6.6% hypo-osmotic stimulus reduces by half the depolarization-evoked vasopressin secretion, an inhibition totally prevented by strychnine. Most importantly, depletion of taurine by a taurine transport inhibitor also abolishes the osmo-dependent inhibition of vasopressin release. Therefore, in the neurohypophysis, an osmoregulatory system involving pituicytes, taurine, and GlyRs is operating to control Ca(2+) influx in and neurohormone release from nerve terminals. This elucidates the functional role of glial taurine in the neurohypophysis, reveals the expression of GlyRs on axon terminals, and further defines the role of glial cells in the regulation of neuroendocrine function. PMID:11549721

  3. Hepatitis

    MedlinePlus

    ... be serious. Some can lead to scarring, called cirrhosis, or to liver cancer. Sometimes hepatitis goes away by itself. If it does not, it can be treated with drugs. Sometimes hepatitis lasts a lifetime. Vaccines can help prevent some viral forms.

  4. Ontogeny of Human Hepatic and Intestinal Transporter Gene Expression during Childhood: Age Matters

    PubMed Central

    Mooij, Miriam G.; Schwarz, Ute I.; de Koning, Barbara A. E.; Leeder, J. Steven; Gaedigk, Roger; Samsom, Janneke N.; Spaans, Edwin; van Goudoever, Johannes B.; Tibboel, Dick; Kim, Richard B.

    2014-01-01

    Many drugs prescribed to children are drug transporter substrates. Drug transporters are membrane-bound proteins that mediate the cellular uptake or efflux of drugs and are important to drug absorption and elimination. Very limited data are available on the effect of age on transporter expression. Our study assessed age-related gene expression of hepatic and intestinal drug transporters. Multidrug resistance protein 2 (MRP2), organic anion transporting polypeptide 1B1 (OATP1B1), and OATP1B3 expression was determined in postmortem liver samples (fetal n = 6, neonatal n = 19, infant n = 7, child n = 2, adult n = 11) and multidrug resistance 1 (MDR1) expression in 61 pediatric liver samples. Intestinal expression of MDR1, MRP2, and OATP2B1 was determined in surgical small bowel samples (neonates n = 15, infants n = 3, adults n = 14). Using real-time reverse-transcription polymerase chain reaction, we measured fetal and pediatric gene expression relative to 18S rRNA (liver) and villin (intestines), and we compared it with adults using the 2−∆∆Ct method. Hepatic expression of MRP2, OATP1B1, and OATP1B3 in all pediatric age groups was significantly lower than in adults. Hepatic MDR1 mRNA expression in fetuses, neonates, and infants was significantly lower than in adults. Neonatal intestinal expressions of MDR1 and MRP2 were comparable to those in adults. Intestinal OATP2B1 expression in neonates was significantly higher than in adults. We provide new data that show organ- and transporter-dependent differences in hepatic and intestinal drug transporter expression in an age-dependent fashion. This suggests that substrate drug absorption mediated by these transporters may be subject to age-related variation in a transporter dependent pattern. PMID:24829289

  5. Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis

    PubMed Central

    Brandoni, Anabel; Hazelhoff, María Herminia; Bulacio, Romina Paula; Torres, Adriana Mónica

    2012-01-01

    Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct. The absorption, distribution and elimination of drugs are impaired during this pathology. Prolonged cholestasis may alter both liver and kidney function. Lactam antibiotics, diuretics, non-steroidal anti-inflammatory drugs, several antiviral drugs as well as endogenous compounds are classified as organic anions. The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds. It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions. The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis, such as multidrug resistance-associated protein 2, organic anion transporting polypeptide 1, organic anion transporter 3, bilitranslocase, bromosulfophthalein/bilirubin binding protein, organic anion transporter 1 and sodium dependent bile salt transporter. The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions. PMID:23197884

  6. Regulation of Human Hepatic Drug Transporter Activity and Expression by Diesel Exhaust Particle Extract

    PubMed Central

    Le Vee, Marc; Jouan, Elodie; Stieger, Bruno; Lecureur, Valérie; Fardel, Olivier

    2015-01-01

    Diesel exhaust particles (DEPs) are common environmental air pollutants primarily affecting the lung. DEPs or chemicals adsorbed on DEPs also exert extra-pulmonary effects, including alteration of hepatic drug detoxifying enzyme expression. The present study was designed to determine whether organic DEP extract (DEPe) may target hepatic drug transporters that contribute in a major way to drug detoxification. Using primary human hepatocytes and transporter-overexpressing cells, DEPe was first shown to strongly inhibit activities of the sinusoidal solute carrier (SLC) uptake transporters organic anion-transporting polypeptides (OATP) 1B1, 1B3 and 2B1 and of the canalicular ATP-binding cassette (ABC) efflux pump multidrug resistance-associated protein 2, with IC50 values ranging from approximately 1 to 20 μg/mL and relevant to environmental exposure situations. By contrast, 25 μg/mL DEPe failed to alter activities of the SLC transporter organic cation transporter (OCT) 1 and of the ABC efflux pumps P-glycoprotein and bile salt export pump (BSEP), whereas it only moderately inhibited those of sodium taurocholate co-transporting polypeptide and of breast cancer resistance protein (BCRP). Treatment by 25 μg/mL DEPe was next demonstrated to induce expression of BCRP at both mRNA and protein level in cultured human hepatic cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B3, OATP2B1, OCT1 and BSEP. Such changes in transporter expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a reference activator of the aryl hydrocarbon receptor (AhR) pathway. This suggests that DEPe, which is enriched in known ligands of AhR like polycyclic aromatic hydrocarbons, alters drug transporter expression via activation of the AhR cascade. Taken together, these data established human hepatic transporters as targets of organic chemicals containing in DEPs, which may contribute to their

  7. Regulation of human hepatic drug transporter activity and expression by diesel exhaust particle extract.

    PubMed

    Le Vee, Marc; Jouan, Elodie; Stieger, Bruno; Lecureur, Valérie; Fardel, Olivier

    2015-01-01

    Diesel exhaust particles (DEPs) are common environmental air pollutants primarily affecting the lung. DEPs or chemicals adsorbed on DEPs also exert extra-pulmonary effects, including alteration of hepatic drug detoxifying enzyme expression. The present study was designed to determine whether organic DEP extract (DEPe) may target hepatic drug transporters that contribute in a major way to drug detoxification. Using primary human hepatocytes and transporter-overexpressing cells, DEPe was first shown to strongly inhibit activities of the sinusoidal solute carrier (SLC) uptake transporters organic anion-transporting polypeptides (OATP) 1B1, 1B3 and 2B1 and of the canalicular ATP-binding cassette (ABC) efflux pump multidrug resistance-associated protein 2, with IC50 values ranging from approximately 1 to 20 μg/mL and relevant to environmental exposure situations. By contrast, 25 μg/mL DEPe failed to alter activities of the SLC transporter organic cation transporter (OCT) 1 and of the ABC efflux pumps P-glycoprotein and bile salt export pump (BSEP), whereas it only moderately inhibited those of sodium taurocholate co-transporting polypeptide and of breast cancer resistance protein (BCRP). Treatment by 25 μg/mL DEPe was next demonstrated to induce expression of BCRP at both mRNA and protein level in cultured human hepatic cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B3, OATP2B1, OCT1 and BSEP. Such changes in transporter expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a reference activator of the aryl hydrocarbon receptor (AhR) pathway. This suggests that DEPe, which is enriched in known ligands of AhR like polycyclic aromatic hydrocarbons, alters drug transporter expression via activation of the AhR cascade. Taken together, these data established human hepatic transporters as targets of organic chemicals containing in DEPs, which may contribute to their

  8. Protein kinase C-dependent regulation of human hepatic drug transporter expression.

    PubMed

    Mayati, Abdullah; Le Vee, Marc; Moreau, Amélie; Jouan, Elodie; Bucher, Simon; Stieger, Bruno; Denizot, Claire; Parmentier, Yannick; Fardel, Olivier

    2015-12-15

    Hepatic drug transporters are now recognized as major actors of hepatobiliary elimination of drugs. Characterization of their regulatory pathways is therefore an important issue. In this context, the present study was designed to analyze the potential regulation of human hepatic transporter expression by protein kinase C (PKC) activation. Treatment by the reference PKC activator phorbol 12-myristate 13-acetate (PMA) for 48h was shown to decrease mRNA expression of various sinusoidal transporters, including OATP1B1, OATP2B1, NTCP, OCT1 and MRP3, but to increase that of OATP1B3, whereas mRNA expression of canalicular transporters was transiently enhanced (MDR1), decreased (BSEP and MRP2) or unchanged (BCRP) in human hepatoma HepaRG cells. The profile of hepatic transporter mRNA expression changes in PMA-treated HepaRG cells was correlated to that found in PMA-exposed primary human hepatocytes and was similarly observed in response to the PKC-activating marketed drug ingenol mebutate. It was associated with concomitant repression of OATP1B1 and OATP2B1 protein expression and reduction of OATP, OCT1, NTCP and MRP2 activity. The use of chemical PKC inhibitors further suggested a contribution of novel PKCs isoforms to PMA-mediated regulations of transporter mRNA expression. PMA was finally shown to cause epithelial-mesenchymal transition (EMT) in HepaRG cells and exposure to various additional EMT inducers, i.e., hepatocyte growth factor, tumor growth factor-β1 or the HNF4α inhibitor BI6015, led to transporter expression alterations highly correlated to those triggered by PMA. Taken together, these data highlight PKC-dependent regulation of human hepatic drug transporter expression, which may be closely linked to EMT triggered by PKC activation. PMID:26462574

  9. Prophylactic and therapeutic effects of taurine against aluminum-induced acute hepatotoxicity in mice.

    PubMed

    El-Sayed, Wael M; Al-Kahtani, Mohamed A; Abdel-Moneim, Ashraf M

    2011-08-30

    Aluminum is a well known neurotoxin and a possible candidate of hepatotoxins to humans. Using natural antioxidants against metal-induced hepatotoxicity is a modern approach. In the present study, Aluminum (AlCl(3)) intoxication (a single injection of 25mg Al(3+)/kg, i.p.) for 24h in mice resulted in elevations in serum alanine aminotransferase activity and serum tumor necrosis factor and hepatic malondialdehyde levels. Aluminum reduced the activities of glutathione peroxidase, glutathione S-transferase, quinone oxidoreductase, and catalase in liver. In addition, Al caused hepatic hemorrhage, cellular degeneration as well as necrosis of hepatocytes. Ultrastructure examination showed swelling of mitochondria, derangement of rough endoplasmic reticulum cisternae and pleomorphic nuclei with abnormal chromatin distribution. Taurine, a sulfur-containing amino acid was administered to mice daily for 5 days before (at 100mg/kg, i.p.) or 2h after (a single dose of 1g/kg, i.p.) aluminum administration. Treating mice with taurine at either dosing regimens, pre- or post-aluminum administration alleviated aluminum oxidative damaging effects. The rate of recovery was better when taurine was administered prior to Al. Taurine had anaphylactic and therapeutic activity against hepatotoxicity induced by aluminum in mice. PMID:21703760

  10. The hepatic bile acid transporters Ntcp and Mrp2 are downregulated in experimental necrotizing enterocolitis

    PubMed Central

    Cherrington, Nathan J.; Estrada, Teresa E.; Frisk, Harrison A.; Canet, Mark J.; Hardwick, Rhiannon N.; Dvorak, Bohuslav; Lux, Katie

    2013-01-01

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants and is characterized by an extensive hemorrhagic inflammatory necrosis of the distal ileum and proximal colon. We have previously shown that, during the development of experimental NEC, the liver plays an important role in regulating inflammation in the ileum, and accumulation of ileal bile acids (BA) along with dysregulation of ileal BA transporters contributes to ileal damage. Given these findings, we speculated that hepatic BA transporters would also be altered in experimental NEC. Using both rat and mouse models of NEC, levels of Cyp7a1, Cyp27a1, and the hepatic BA transporters Bsep, Ntcp, Oatp2, Oatp4, Mrp2, and Mrp3 were investigated. In addition, levels of hepatic BA transporters were also determined when the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-18, which are both elevated in NEC, are neutralized during disease development. Ntcp and Mrp2 were decreased in NEC, but elevated ileal BA levels were not responsible for these reductions. However, neutralization of TNF-α normalized Ntcp, whereas removal of IL-18 normalized Mrp2 levels. These data show that the hepatic transporters Ntcp and Mrp2 are downregulated, whereas Cyp27a1 is increased in rodent models of NEC. Furthermore, increased levels of TNF-α and IL-18 in experimental NEC may play a role in the regulation of Ntcp and Mrp2, respectively. These data suggest the gut-liver axis should be considered when therapeutic modalities for NEC are developed. PMID:23125159

  11. Hepatic and renal Bcrp transporter expression in mice treated with perfluorooctanoic acid

    PubMed Central

    Eldasher, Lobna M.; Wen, Xia; Little, Michael S.; Bircsak, Kristin M.; Yacovino, Lindsay L.; Aleksunes, Lauren M.

    2013-01-01

    The breast cancer resistance protein (Bcrp) is an efflux transporter that participates in the biliary and renal excretion of drugs and environmental chemicals. Recent evidence suggests that pharmacological activation of the peroxisome proliferator activated receptor alpha (PPARα) can up-regulate the hepatic expression of Bcrp. The current study investigated the regulation of hepatic and renal Bcrp mRNA and protein in mice treated with the PPARα agonist perfluorooctanoic acid (PFOA) and the ability of PFOA to alter human BCRP function in vitro. Bcrp mRNA and protein expression were quantified in the livers and kidneys of male C57BL/6 mice treated with vehicle or PFOA (1 or 3 mg/kg/day oral gavage) for 7 days. PFOA treatment increased liver weights as well as the hepatic mRNA and protein expression of the PPARα target gene, cytochrome P450 4a14. Compared to vehicle-treated control mice, PFOA increased hepatic Bcrp mRNA and protein between 1.5- and 3-fold. Immunofluorescent staining confirmed enhanced canalicular Bcrp staining in liver sections from PFOA-treated mice. The kidney expression of cytochrome P450 4a14 mRNA, but not Bcrp, was increased in mice treated with PFOA. Micromolar concentrations of PFOA decreased human BCRP ATPase activity and inhibited BCRP-mediated transport in inverted membrane vesicles. Together, these studies demonstrate that PFOA induces hepatic Bcrp expression in mice and may inhibit human BCRP transporter function at concentrations that exceed levels observed in humans. PMID:23435180

  12. AQUACAT: A TAURINE REQUIREMENT FOR COBIA.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In most animals, taurine is synthesized from methionine and cysteine. However, due to inadequacy of enzymatic machinery involved in taurine synthesis, it is considered an essential amino acid (EAA) for cats. Cobia (Rachycentron canadum) are marine carnivorous fishes with global distribution. In fish...

  13. 21 CFR 573.980 - Taurine.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food...

  14. 21 CFR 573.980 - Taurine.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food...

  15. 21 CFR 573.980 - Taurine.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food...

  16. 21 CFR 573.980 - Taurine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food...

  17. 21 CFR 573.980 - Taurine.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Taurine. 573.980 Section 573.980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.980 Taurine. The food...

  18. Manganese exposure inhibits the clearance of extracellular GABA and influences taurine homeostasis in the striatum of developing rats

    PubMed Central

    Fordahl, Steve C.; Anderson, Joel G.; Cooney, Paula T.; Weaver, Tara L.; Colyer, Christa L.; Erikson, Keith M.

    2010-01-01

    Manganese (Mn) accumulation in the brain has been shown to alter the neurochemistry of the basal ganglia. Mn-induced alterations in dopamine biology are fairly well understood, but recently more evidence has emerged characterizing the role of γ-aminobutyric acid (GABA) in this dysfunction. The purpose of this study was to determine if the previously observed Mn-induced increase in extracellular GABA (GABAEC) was due to altered GABA transporter (GAT) function, and whether Mn perturbs other amino acid neurotransmitters, namely taurine and glycine (known modulators of GABA). Extracellular GABA, taurine, and glycine concentrations were collected from the striatum of control (CN) or Mn-exposed Sprague-Dawley rats using in vivo microdialysis, and the GAT inhibitor nipecotic acid (NA) was used to probe GAT function. Tissue and extracellular Mn levels were significantly increased, and the Fe:Mn ratio was decreased 36-fold in the extracellular space due to Mn exposure. NA led to a 2-fold increase in GABAEC of CNs, a response that was attenuated by Mn. Taurine responded inversely to GABA, and a novel 10-fold increase in taurine was observed after the removal of NA in CNs. Mn blunted this response and nearly abolished extracellular taurine throughout collection. Striatal taurine transporter (Slc6a6) mRNA levels were significantly increased with Mn exposure, and Mn significantly increased 3H-Taurine uptake after 3-minute exposure in primary rat astrocytes. These data suggest that Mn increases GABAEC by inhibiting the function of GAT, and that perturbed taurine homeostasis potentially impacts neural function by jeopardizing the osmoregulatory and neuromodulatory functions of taurine in the brain. PMID:20832424

  19. Organic anion transporting polypeptides in the hepatic uptake of PBDE congeners in mice

    SciTech Connect

    Pacyniak, Erik; Hagenbuch, Bruno; The University of Kansas Cancer Center, Kansas City, KS ; Klaassen, Curtis D.; Lehman-McKeeman, Lois; Guo, Grace L.

    2011-11-15

    BDE47, BDE99 and BDE153 are the predominant polybrominated diphenyl ether (PBDE) congeners detected in humans and can induce drug metabolizing enzymes in the liver. We have previously demonstrated that several human liver organic anion transporting polypeptides (humans: OATPs; rodents: Oatps) can transport PBDE congeners. Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. However, the mechanism of the hepatic PBDE uptake in mice is not known. Therefore, the purpose of the current study was to test the hypothesis that BDE47, BDE99, and BDE153 are substrates of mouse hepatic Oatps (Oatp1a1, Oatp1a4, Oatp1b2, and Oatp2b1). We used Human Embryonic Kidney 293 (HEK293) cells transiently expressing individual Oatps and quantified the uptake of BDE47, BDE99, and BDE153. Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners, whereas Oatp1a1 did transport none. Kinetic studies demonstrated that Oatp1a4 and Oatp1b2 transported BDE47 with the greatest affinity, followed by BDE99 and BDE153. In contrast, Oatp2b1 transported all three PBDE congeners with similar affinities. The importance of hepatic Oatps for the liver accumulation of BDE47 was confirmed using Oatp1a4-, and Oatp1b2-null mice. -- Highlights: Black-Right-Pointing-Pointer PBDE congeners are substrates of OATPs expressed in human hepatocytes. Black-Right-Pointing-Pointer Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. Black-Right-Pointing-Pointer Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners in vitro. Black-Right-Pointing-Pointer In vivo Oatp1a4 plays a minor and Oatp1b2 a major role in BDE47 liver accumulation.

  20. Chlorination of Taurine by Human Neutrophils

    PubMed Central

    Weiss, Stephen J.; Klein, Roger; Slivka, Adam; Wei, Maria

    1982-01-01

    The model hydrogen peroxide-myeloperoxidase-chloride system is capable of generating the powerful oxidant hypochlorous acid, which can be quantitated by trapping the generated species with the β-amino acid, taurine. The resultant stable product, taurine chloramine, can be quantitated by its ability to oxidize the sulfhydryl compound, 5-thio-2-nitro-benzoic acid to the disulfide, 5,5′-dithiobis(2-nitroben-zoic acid) or to oxidize iodide to iodine. Using this system, purified myeloperoxidase in the presence of chloride and taurine converted stoichiometric quantities of hydrogen peroxide to taurine chloramine. Chloramine generation was absolutely dependent on hydrogen peroxide, myeloperoxidase, and chloride and could be inhibited by catalase, myeloperoxidase inhibitors, or chloride-free conditions. In the presence of taurine, intact human neutrophils stimulated with either phorbol myristate acetate or opsonized zymosan particles generated a stable species capable of oxidizing 5-thio-2-nitrobenzoic acid or iodide. Resting cells did not form this species. The oxidant formed by the stimulated neutrophils was identified as taurine chloramine by both ultraviolet spectrophotometry and electrophoresis. Taurine chloramine formation by the neutrophil was dependent on the taurine concentration, time, and cell number. Neutrophil-dependent chloramine generation was inhibited by catalase, the myeloperoxidase inhibitors, azide, cyanide, or aminotriazole and by chloride-free conditions, but not by superoxide dismutase or hydroxyl radical scavengers. Thus, it appears that stimulated human neutrophils can utilize the hydrogen peroxide-myeloperoxidase-chloride system to generate taurine chloramine. Based on the demonstrated ability of the myeloperoxidase system to generate free hypochlorous acid we conclude that neutrophils chlorinate taurine by producing this powerful oxidant. The biologic reactivity and cytotoxic potential of hypochlorous acid and its chloramine derivatives

  1. Regulation of hepatic ABCC transporters by xenobiotics and in disease states

    PubMed Central

    Gu, Xinsheng; Manautou, Jose E.

    2015-01-01

    The subfamily of ABCC transporters consists of 13 members in mammals, including the multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and the cystic fibrosis transmembrane conductance regulator (CFTR). These proteins play roles in chemical detoxification, disposition, and normal cell physiology. ABCC transporters are expressed differentially in the liver and are regulated at the transcription and translation level. Their expression and function are also controlled by post-translational modification and membrane-trafficking events. These processes are tightly regulated. Information about alterations in the expression of hepatobiliary ABCC transporters could provide important insights into the pathogenesis of diseases and disposition of xenobiotics. In this review, we describe the regulation of hepatic ABCC transporters in humans and rodents by a variety of xenobiotics, under disease states and in genetically modified animal models deficient in transcription factors, transporters, and cell-signaling molecules. PMID:20233023

  2. Advances in Drug Design Based on the Amino Acid Approach: Taurine Analogues for the Treatment of CNS Diseases

    PubMed Central

    Chung, Man Chin; Malatesta, Pedro; Bosquesi, Priscila Longhin; Yamasaki, Paulo Renato; dos Santos, Jean Leandro; Vizioli, Ednir Oliveira

    2012-01-01

    Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid) this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer’s, Parkinson’s, epilepsy and in the damage of retinal neurons. This review describes the CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment. PMID:24281261

  3. Clinical CYP3A inhibitor alternatives to ketoconazole, clarithromycin and itraconazole, are not transported into the liver by hepatic organic anion transporting polypeptides and organic cation transporter 1.

    PubMed

    Higgins, J William; Ke, Alice B; Zamek-Gliszczynski, Maciej J

    2014-11-01

    Ketoconazole is no longer available for clinical determination of worst-case victim drug-drug interaction (DDI) potential for cytochrome P450 3A (CYP3A)-substrate drugs; clarithromycin and itraconazole are the proposed replacements. Ketoconazole DDIs are described by unbound systemic exposures due to absence of carrier-facilitated hepatic uptake, but this aspect of clarithromycin and itraconazole disposition has not been investigated. At present, transport of clarithromycin, itraconazole, and hydroxyitraconazole by hepatic organic anion transporting polypeptides (OATPs) and organic cation transporter 1 (OCT1) was examined in vitro and in vivo. As for ketoconazole, uptake of clarithromycin, itraconazole, and hydroxyitraconazole into OATP1B1, OATP1B3, OATP2B1, and OCT1 expressing human embryonic kidney 293 (HEK293) cells was not greater than in vector controls. Uptake into these HEK293 cells and human hepatocytes was not impaired by the prototypical OATP, OCT, and sodium/taurocholate cotransporting polypeptide inhibitors bromosulfophthalein, imipramine, and taurocholate, respectively. In contrast, uptake of the positive controls, atorvastatin for OATPs and metformin for OCT1, was significantly enhanced by relevant transporter expression, and uptake into both these HEK293 cells and human hepatocytes was significantly impaired by prototypical inhibitors. In Oatp1a/1b gene cluster knockout mice, which lack the major hepatic Oatps, and in Oct1/2 knockout mice, ketoconazole, clarithromycin, itraconazole, and hydroxyitraconazole oral exposure was not increased, and the liver-to-blood partition coefficient (Kp) was not decreased. By contrast relative to wild-type mice, in Oatp1a/1b- and Oct1/2-knockout mice, atorvastatin and metformin oral exposure was significantly increased, and liver Kp was significantly decreased. The present studies provide in vitro and in vivo evidence that, like ketoconazole, clarithromycin, itraconazole, and hydroxyitraconazole are not transported

  4. Knockout of the murine cysteine dioxygenase gene results in severe impairment in ability to synthesize taurine and an increased catabolism of cysteine to hydrogen sulfide

    PubMed Central

    Ueki, Iori; Roman, Heather B.; Valli, Alessandro; Fieselmann, Krista; Lam, Jimmy; Peters, Rachel; Hirschberger, Lawrence L.

    2011-01-01

    Cysteine homeostasis is dependent on the regulation of cysteine dioxygenase (CDO) in response to changes in sulfur amino acid intake. CDO oxidizes cysteine to cysteinesulfinate, which is further metabolized to either taurine or to pyruvate plus sulfate. To gain insight into the physiological function of CDO and the consequence of a loss of CDO activity, mice carrying a null CDO allele (CDO+/− mice) were crossed to generate CDO−/−, CDO+/−, and CDO+/+ mice. CDO−/− mice exhibited postnatal mortality, growth deficit, and connective tissue pathology. CDO−/− mice had extremely low taurine levels and somewhat elevated cysteine levels, consistent with the lack of flux through CDO-dependent catabolic pathways. However, plasma sulfate levels were slightly higher in CDO−/− mice than in CDO+/− or CDO+/+ mice, and tissue levels of acid-labile sulfide were elevated, indicating an increase in cysteine catabolism by cysteine desulfhydration pathways. Null mice had lower hepatic cytochrome c oxidase levels, suggesting impaired electron transport capacity. Supplementation of mice with taurine improved survival of male pups but otherwise had little effect on the phenotype of the CDO−/− mice. H2S has been identified as an important gaseous signaling molecule as well as a toxicant, and pathology may be due to dysregulation of H2S production. Control of cysteine levels by regulation of CDO may be necessary to maintain low H2S/sulfane sulfur levels and facilitate the use of H2S as a signaling molecule. PMID:21693692

  5. Altered regulation of hepatic efflux transporters disrupts acetaminophen disposition in pediatric nonalcoholic steatohepatitis.

    PubMed

    Canet, Mark J; Merrell, Matthew D; Hardwick, Rhiannon N; Bataille, Amy M; Campion, Sarah N; Ferreira, Daniel W; Xanthakos, Stavra A; Manautou, Jose E; A-Kader, H Hesham; Erickson, Robert P; Cherrington, Nathan J

    2015-06-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, representing a spectrum of liver pathologies that include simple hepatic steatosis and the more advanced nonalcoholic steatohepatitis (NASH). The current study was conducted to determine whether pediatric NASH also results in altered disposition of acetaminophen (APAP) and its two primary metabolites, APAP-sulfate and APAP-glucuronide. Pediatric patients with hepatic steatosis (n = 9) or NASH (n = 3) and healthy patients (n = 12) were recruited in a small pilot study design. All patients received a single 1000-mg dose of APAP. Blood and urine samples were collected at 1, 2, and 4 hours postdose, and APAP and APAP metabolites were determined by high-performance liquid chromatography. Moreover, human liver tissues from patients diagnosed with various stages of NAFLD were acquired from the Liver Tissue Cell Distribution System to investigate the regulation of the membrane transporters, multidrug resistance-associated protein 2 and 3 (MRP2 and MRP3, respectively). Patients with the more severe disease (i.e., NASH) had increased serum and urinary levels of APAP-glucuronide along with decreased serum levels of APAP-sulfate. Moreover, an induction of hepatic MRP3 and altered canalicular localization of the biliary efflux transporter, MRP2, describes the likely mechanism for the observed increase in plasma retention of APAP-glucuronide, whereas altered regulation of sulfur activation genes may explain decreased sulfonation activity in NASH. APAP-glucuronide and APAP-sulfate disposition is altered in NASH and is likely due to hepatic membrane transporter dysregulation as well as altered intracellular sulfur activation. PMID:25788542

  6. Proteomic analysis for the impact of hypercholesterolemia on expressions of hepatic drug transporters and metabolizing enzymes.

    PubMed

    Liu, Yan; Pu, Qiang-Hong; Wu, Ming-Jun; Yu, Chao

    2016-10-01

    1. Our objective is to investigate the alterations of hepatic drug transporters and metabolizing enzymes in hypercholesterolemia. Male Sprague-Dawley rats were fed high-cholesterol chows for 8 weeks to induce hypercholesterolemia. Protein levels of hepatic drug transporters and metabolizing enzymes were analyzed by iTRAQ labeling coupled with LC TRIPLE-TOF. 2. Total 239 differentially expressed proteins were identified using proteomic analysis. Among those, protein levels of hepatic drug transporters (MRP2, ABCD3, OAT2, SLC25A12, SCL38A3, SLC2A2 and SLC25A5) and metabolizing enzymes (CYP2B3, CYP2C7, CYP2C11, CYP2C13, CYP4A2 and UGT2B) were markedly reduced, but the levels of CYP2C6 and CYP2E1 were increased in hypercholesterolemia group compared to control. Decreased expressions of drug transporters MRP2 and OAT2 were further confirmed by real time quantitative PCR (RT-qPCR) and western blot. 3. Ingenuity pathway analysis revealed that these differentially expressed proteins were regulated by various signaling pathways including nuclear receptors and inflammatory cytokines. One of the nuclear receptor candidates, liver X receptor alpha (LXRα), was further validated by RT-qPCR and western blot. Additionally, LXRα agonist T0901317 rescued the reduced expressions of MRP2 and OAT2 in HepG2 cells in hypercholesterolemic serum treatment. 4. Our present results indicated that hypercholesterolemia affected the expressions of various drug transporters and metabolizing enzymes in liver via nuclear receptors pathway. Especially, decreased function of LXRα contributes to the reduced expressions of MRP2 and OAT2. PMID:26887802

  7. The evolution of the OATP hepatic uptake transport protein family in DMPK sciences: from obscure liver transporters to key determinants of hepatobiliary clearance.

    PubMed

    Fenner, Katherine S; Jones, Hannah M; Ullah, Mohammed; Kempshall, Sarah; Dickins, Maurice; Lai, Yurong; Morgan, Paul; Barton, Hugh A

    2012-01-01

    Over the last two decades the impact on drug pharmacokinetics of the organic anion transporting polypeptides (OATPs: OATP-1B1, 1B3 and 2B1), expressed on the sinusoidal membrane of the hepatocyte, has been increasingly recognized. OATP-mediated uptake into the hepatocyte coupled with subsequent excretion into bile via efflux proteins, such as MRP2, is often referred to as hepatobiliary excretion. OATP transporter proteins can impact some drugs in several ways including pharmacokinetic variability, pharmacodynamic response and drug-drug interactions (DDIs). The impact of transporter mediated hepatic clearance is illustrated with case examples, from the literature and also from the Pfizer portfolio. The currently available in vitro techniques to study the hepatic transporter proteins involved in the hepatobiliary clearance of drugs are reviewed herein along with recent advances in using these in vitro data to predict the human clearance of compounds recognized by hepatic uptake transporters. PMID:22077101

  8. Hepatitis D Virus Infection of Mice Expressing Human Sodium Taurocholate Co-transporting Polypeptide

    PubMed Central

    Mao, Fengfeng; Jing, Zhiyi; Li, Yunfei; Liu, Yang; Peng, Bo; Yan, Huan; Qi, Yonghe; Sun, Yinyan; Guo, Ju-Tao; Sui, Jianhua; Wang, Fengchao; Li, Wenhui

    2015-01-01

    Hepatitis D virus (HDV) is the smallest virus known to infect human. About 15 million people worldwide are infected by HDV among those 240 million infected by its helper hepatitis B virus (HBV). Viral hepatitis D is considered as one of the most severe forms of human viral hepatitis. No specific antivirals are currently available to treat HDV infection and antivirals against HBV do not ameliorate hepatitis D. Liver sodium taurocholate co-transporting polypeptide (NTCP) was recently identified as a common entry receptor for HDV and HBV in cell cultures. Here we show HDV can infect mice expressing human NTCP (hNTCP-Tg). Antibodies against critical regions of HBV envelope proteins blocked HDV infection in the hNTCP-Tg mice. The infection was acute yet HDV genome replication occurred efficiently, evident by the presence of antigenome RNA and edited RNA species specifying large delta antigen in the livers of infected mice. The resolution of HDV infection appears not dependent on adaptive immune response, but might be facilitated by innate immunity. Liver RNA-seq analyses of HDV infected hNTCP-Tg and type I interferon receptor 1 (IFNα/βR1) null hNTCP-Tg mice indicated that in addition to induction of type I IFN response, HDV infection was also associated with up-regulation of novel cellular genes that may modulate HDV infection. Our work has thus proved the concept that NTCP is a functional receptor for HDV infection in vivo and established a convenient small animal model for investigation of HDV pathogenesis and evaluation of antiviral therapeutics against the early steps of infection for this important human pathogen. PMID:25902143

  9. A case of taurine-containing drink induced anaphylaxis.

    PubMed

    Lee, Seung-Eun; Lee, Suh-Young; Jo, Eun-Jung; Kim, Mi-Young; Yang, Min-Suk; Chang, Yoon-Seok; Kim, Sae-Hoon

    2013-01-01

    Taurine is one of most abundant free amino acids in mammalian tissue. It has been used for various health functional foods as a main ingredient in food industry. A 33-year-old female patient repeatedly experienced generalized itching, urticaria, dyspnea and dizziness after drinking taurine-containing drinks. The patient showed positive response to oral challenge tests with taurine-containing drinks. The patient also showed positive response with synthetic taurine but not with natural taurine. Skin prick test and basophil activation test with the synthetic taurine were negative. To our knowledge, there has been no report of taurine-induced hypersensitivity reactions. We herein report the first case of taurine-containing drink induced anaphylaxis, especially by synthetic taurine. PMID:23404176

  10. Taurine Boosts Cellular Uptake of Small D-Peptides for Enzyme-Instructed Intracellular Molecular Self-Assembly.

    PubMed

    Zhou, Jie; Du, Xuewen; Li, Jie; Yamagata, Natsuko; Xu, Bing

    2015-08-19

    Due to their biostability, D-peptides are emerging as an important molecular platform for biomedical applications. Being proteolytically resistant, D-peptides lack interactions with endogenous transporters and hardly enter cells. Here we show that taurine, a natural amino acid, drastically boosts the cellular uptake of small D-peptides in mammalian cells by >10-fold, from 118 μM (without conjugating taurine) to >1.6 mM (after conjugating taurine). The uptake of a large amount of the ester conjugate of taurine and D-peptide allows intracellular esterase to trigger intracellular self-assembly of the D-peptide derivative, further enhancing their cellular accumulation. The study on the mechanism of the uptake reveals that the conjugates enter cells via both dynamin-dependent endocytosis and macropinocytosis, but likely not relying on taurine transporters. Differing fundamentally from the positively charged cell-penetrating peptides, the biocompatibility, stability, and simplicity of the enzyme-cleavable taurine motif promise new ways to promote the uptake of bioactive molecules for countering the action of efflux pump and contributing to intracellular molecular self-assembly. PMID:26235707

  11. Taurine Boosts Cellular Uptake of Small d-Peptides for Enzyme-Instructed Intracellular Molecular Self-Assembly

    PubMed Central

    2016-01-01

    Due to their biostability, d-peptides are emerging as an important molecular platform for biomedical applications. Being proteolytically resistant, d-peptides lack interactions with endogenous transporters and hardly enter cells. Here we show that taurine, a natural amino acid, drastically boosts the cellular uptake of small d-peptides in mammalian cells by >10-fold, from 118 μM (without conjugating taurine) to >1.6 mM (after conjugating taurine). The uptake of a large amount of the ester conjugate of taurine and d-peptide allows intracellular esterase to trigger intracellular self-assembly of the d-peptide derivative, further enhancing their cellular accumulation. The study on the mechanism of the uptake reveals that the conjugates enter cells via both dynamin-dependent endocytosis and macropinocytosis, but likely not relying on taurine transporters. Differing fundamentally from the positively charged cell-penetrating peptides, the biocompatibility, stability, and simplicity of the enzyme-cleavable taurine motif promise new ways to promote the uptake of bioactive molecules for countering the action of efflux pump and contributing to intracellular molecular self-assembly. PMID:26235707

  12. The first supramolecular peptidic hydrogelator containing taurine

    PubMed Central

    Kuang, Yi; Gao, Yuan; Shi, Junfeng; Li, Jie; Xu, Bing

    2014-01-01

    The conjugation of taurine with a dipeptide derivative affords a cell compatible, small molecular hydrogelator to form hydrogels that exhibit rich phase transition behaviors response to sonication and the change of pH or temperature. PMID:24480853

  13. A specific taurine recognition site in the rabbit brain is responsible for taurine effects on thermoregulation

    PubMed Central

    Frosini, Maria; Sesti, Casilde; Saponara, Simona; Ricci, Lorenzo; Valoti, Massimo; Palmi, Mitri; Machetti, Fabrizio; Sgaragli, Giampietro

    2003-01-01

    Taurine and GABA are recognized as endogenous cryogens. In a previous study, some structural analogues of taurine, namely 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2-hydroxyethanesulfonic (ISE) and (±)cis-2-aminocyclohexane sulfonic acids (CAHS) have been shown to displace [3H]taurine binding from rabbit brain synaptic membrane preparations, without interacting either with GABA-ergic systems, nor with taurine uptake mechanism, thus behaving like direct taurinergic agents. To answer the question whether the role of taurine as an endogenous cryogen depends on the activation of GABA receptors or that of specific taurine receptor(s), taurine or the above structural analogues were injected intracerebroventricularly in conscious, restrained rabbits singularly or in combination and their effects on rectal (RT)- and ear–skin temperature and gross motor behavior (GMB) were monitored. Taurine (1.2 × 10−6–4.8 × 10−5 mol) induced a dose-related hypothermia, vasodilation at ear vascular bed and inhibition of GMB. CAHS, at the highest dose tested (4.8 × 10−5 mol) induced a taurine-like effect either on RT or GMB. On the contrary ISE, injected at the same doses of taurine, induced a dose-related hyperthermia, vasoconstriction and excitation of GMB. AEA and TAG caused a dose-related hyperthermia, but at doses higher than 1.2 × 10−7 mol caused death within 24 h after treatment. CAHS (4.8 × 10−5 mol) antagonized the hyperthermic effect induced by TAG (1.2 × 10−6 mol), AEA (1.2 × 10−8 mol) or ISE (4.8 × 10−5 mol). In conclusion, these findings may indicate the existence of a recognition site specific for taurine, responsible for its effects on thermoregulation. PMID:12788808

  14. HPLC Determination of Taurine in Sports Drinks

    NASA Astrophysics Data System (ADS)

    Orth, Dale L.

    2001-06-01

    The amino acid taurine (2-aminoethanesulfonic acid) is present as a nutritional supplement in many sports drinks. An experiment, suitable for a junior-senior level instrumental analysis course, is described to measure the amount of taurine in these sports drinks. A pre-column derivatization with Sanger's reagent, 2,4-dinitrofluorobenzene, is followed by an HPLC separation utilizing a gradient elution, and detection at 360 nm.

  15. [Taurine chloramine and its potential therapeutical application].

    PubMed

    Walczewska, Maria; Marcinkiewicz, Janusz

    2011-01-01

    Taurine chloramine (TauCl) is generated at the site of inflammation as a result of reaction of taurine with hypochlorous acid (HOCl), the product of myeloperoxidase-halide system of neutrophils. It has been shown in vitro that TauCl exerts both anti-inflammatory and anti-microbial properties. This review is an attempt to summarize the recent clinical studies in which TauCl was used for local treatment of infectious and inflammatory diseases. PMID:22039673

  16. Signals for Bidirectional Nucleocytoplasmic Transport in the Duck Hepatitis B Virus Capsid Protein

    PubMed Central

    Mabit, Helene; Breiner, Klaus M.; Knaust, Andreas; Zachmann-Brand, Beate; Schaller, Heinz

    2001-01-01

    Hepadnavirus genome replication involves cytoplasmic and nuclear stages, requiring balanced targeting of cytoplasmic nucleocapsids to the nuclear compartment. In this study, we analyze the signals determining capsid compartmentalization in the duck hepatitis B virus (DHBV) animal model, as this system also allows us to study hepadnavirus infection of cultured primary hepatocytes. Using fusions to the green fluorescent protein as a functional assay, we have identified a nuclear localization signal (NLS) that mediates nuclear pore association of the DHBV nucleocapsid and nuclear import of DHBV core protein (DHBc)-derived polypeptides. The DHBc NLS mapped is unique. It bears homology to repetitive NLS elements previously identified near the carboxy terminus of the capsid protein of hepatitis B virus, the human prototype of the hepadnavirus family, but it maps to a more internal position. In further contrast to the hepatitis B virus core protein NLS, the DHBc NLS is not positioned near phosphorylation target sites that are generally assumed to modulate nucleocytoplasmic transport. In functional assays with a knockout mutant, the DHBc NLS was found to be essential for nuclear pore association of the nucleocapsid. The NLS was found to be also essential for virus production from the full-length DHBV genome in transfected cells and from hepatocytes infected with transcomplemented mutant virus. Finally, the DHBc additionally displayed activity indicative of a nuclear export signal, presumably counterbalancing NLS function in the productive state of the infected cell and thereby preventing nucleoplasmic accumulation of nucleocapsids. PMID:11160696

  17. Characterization of nuclear targeting signal of hepatitis delta antigen: nuclear transport as a protein complex.

    PubMed Central

    Xia, Y P; Yeh, C T; Ou, J H; Lai, M M

    1992-01-01

    Hepatitis delta antigen (HDAg) is the only protein encoded by hepatitis delta virus (HDV). HDAg has been demonstrated in the nuclei of HDV-infected hepatocytes, and its nuclear transport may be important for the replication of HDV RNA. In this report, we investigated the mechanism of nuclear transport of HDAg. By expressing fusion proteins consisting of the different portions of HDAg and alpha-globin, we have identified a nuclear localization signal (NLS) within the N-terminal one-third of HDAg. It consists of two stretches of basic amino acid domains separated by a short run of nonbasic amino acids. Both of the basic domains are necessary for the efficient nuclear transport of HDAg. The nonbasic spacer amino acids could be removed without affecting the nuclear targeting of HDAg significantly. Thus, the HDAg NLS belongs to a newly identified class of NLS which consists of two discontiguous stretches of basic amino acids. This NLS is separated from a stretch of steroid receptor NLS-like sequence, which is also present but not functioning as an NLS, in HDAg. Furthermore, we have shown that subfragments of HDAg which do not contain the NLS can be passively transported into the nucleus by a trans-acting full-length HDAg, provided that these subfragments contain the region with a leucine zipper sequence. Thus, our results indicate that HDAg forms aggregates in the cytoplasm and that the HDAg oligomerization is probably mediated by the leucine zipper sequence. Therefore, HDAg is likely transported into the nucleus as a protein complex. Images PMID:1731113

  18. Combined administration of taurine and meso 2,3-dimercaptosuccinic acid in the treatment of chronic lead intoxication in rats.

    PubMed

    Flora, S J S; Pande, Manisha; Bhadauria, Smrati; Kannan, G M

    2004-04-01

    The present study describes the dose-dependent effect of taurine, an amino acid and a known antioxidant, either alone or in combination with meso 2,3-dimercaptosuccinic acid (DMSA) in the treatment of subchronic lead intoxication in male rats. The effects of these treatments in influencing the lead-induced alterations in haem synthesis, hepatic, renal or brain oxidative stress and lead concentration from soft tissues were investigated. Exposure to lead produced a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD) activity, reduction in glutathione (GSH) and an increase in zinc protoporphyrin (ZPP) suggesting an altered haem synthesis pathway. Only DMSA was able to increase the activity of ALAD, while both taurine and DMSA were able to significantly increase GSH level towards normal. Animals treated with taurine significantly reduced the alterations in some of the biochemical parameters indicative of oxidative stress. Thiobarbituric acid reactive substance (TBARS) levels reduced significantly in liver, kidney and red blood cells, while GSH level increased. Activity of superoxide dismutase (SOD) also showed an increase in blood and brain in animals treated with taurine. The data also provided a promising role of taurine during chelation of lead by potentiating the depletion of blood, liver and brain lead compared to DMSA alone. It can thus be concluded from the study that concomitant administration of an antioxidant could play a significant and important role in abating a number of toxic effects of lead when administered along with the thiol chelators. PMID:15171566

  19. Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance

    PubMed Central

    Dietrich, Christoph G; Götze, Oliver; Geier, Andreas

    2016-01-01

    Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma. The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function. This review summarizes the regulatory and functional changes in phase I and phase II metabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients. Interestingly, phase I enzymes are generally downregulated transcriptionally, while phase II enzymes are mostly preserved transcriptionally but are reduced in their function. Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis. Lipid and glucose metabolism are characterized by insulin resistance and catabolism, leading to the disturbance of energy expenditure and wasting. Possible non-invasive tests, especially breath tests, for components of liver metabolism are discussed. The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients. Additionally, studies in humans are rare, and species differences preclude the transferability of data from rodents to humans. In clinical practice, some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis, but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests. PMID:26755861

  20. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    PubMed

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P < 0.01), respectively, and (2) that taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P < 0.01), respectively. Overall, our results indicated that taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR. PMID:24676564

  1. Variability in hepatic expression of organic anion transporter 7/SLC22A9, a novel pravastatin uptake transporter: impact of genetic and regulatory factors.

    PubMed

    Emami Riedmaier, A; Burk, O; van Eijck, B A C; Schaeffeler, E; Klein, K; Fehr, S; Biskup, S; Müller, S; Winter, S; Zanger, U M; Schwab, M; Nies, A T

    2016-08-01

    Human organic anion transporter 7 (OAT7, SLC22A9) is a hepatic transport protein poorly characterized so far. We therefore sought to identify novel OAT7 substrates and factors contributing to variable hepatic OAT7 expression. Using OAT7-expressing cells, pravastatin was identified as a substrate. Hepatic SLC22A9/OAT7 mRNA and protein expression varied 28-fold and 15-fold, respectively, in 126 Caucasian liver samples. Twenty-four variants in SLC22A9 were genotyped, including three rare missense variants (rs377211288, rs61742518, rs146027075), which occurred only heterozygously. No variant significantly affected hepatic SLC22A9/OAT7 expression. The three missense variants, however, showed functional consequences when expressed in vitro. Hepatic nuclear factor 4-alpha (HNF4α) emerged as a major transcriptional regulator of SLC22A9 by a series of in silico and in vitro analyses. In conclusion, pravastatin is the first identified OAT7 drug substrate. Substantial inter-individual variability in hepatic OAT7 expression, majorly driven by HNF4α, may contribute to pravastatin drug disposition and might affect response.The Pharmacogenomics Journal advance online publication, 4 August 2015; doi:10.1038/tpj.2015.55. PMID:26239079

  2. Effects of graded taurine levels on juvenile cobia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Taurine, which has multiple important physiological roles in teleost fish and mammals, is an amino acid not found in alternative protein sources not derived from animals. Although taurine is found in fish-meal-based feeds, its high water solubility leads to lower taurine levels in reduction-process-...

  3. The Altered Renal and Hepatic Expression of Solute Carrier Transporters (SLCs) in Type 1 Diabetic Mice

    PubMed Central

    Xu, Chenghao; Zhu, Ling; Chan, Ting; Lu, Xiaoxi; Shen, Weiyong; Gillies, Mark C.; Zhou, Fanfan

    2015-01-01

    Diabetes mellitus is a chronic metabolic disorder that significantly affects human health and well-being. The Solute carrier transporters (SLCs), particularly the Organic anion/cation transporters (Oats/Octs/Octns), Organic anion transporting polypeptides (Oatps) and Oligopeptide transporters (Pepts) are essential membrane proteins responsible for cellular uptake of many endogenous and exogenous substances such as clinically important drugs. They are widely expressed in mammalian key organs especially the kidney and liver, in which they facilitate the influx of various drug molecules, thereby determining their distribution and elimination in body. The altered expression of SLCs in diabetes mellitus could have a profound and clinically significant influence on drug therapies. In this study, we extensively investigated the renal and hepatic expression of twenty essential SLCs in the type 1 diabetic Ins2Akita murine model that develops both hyperglycemia and diabetes-related complications using real-time PCR and immunoblotting analysis. We found that the renal expression of mOatp1a1, mOatp1a6, mOat1, mOat3, mOat5, mOct2 and mPept2 was decreased; while that of mPept1 was increased at the mRNA level in the diabetic mice compared with non-diabetic controls. We found up-regulated mRNA expression of mOatp1a4, mOatp1c1, mOctn2, mOct3 and mPept1 as well as down-regulation of mOatp1a1 in the livers of diabetic mice. We confirmed the altered protein expression of several SLCs in diabetic mice, especially the decreased renal and hepatic expression of mOatp1a1. We also found down-regulated protein expression of mOat3 and mOctn1 in the kidneys as well as increased protein expression of mOatp1a4 and mOct3 in the livers of diabetic mice. Our findings contribute to better understanding the modulation of SLC transporters in type 1 diabetes mellitus, which is likely to affect the pharmacokinetic performance of drugs that are transported by these transporters and therefore, forms the

  4. Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats.

    PubMed

    Flora, Swaran J S; Chouhan, Swapnila; Kannan, Gurusamy M; Mittal, Megha; Swarnkar, Harimohan

    2008-01-01

    Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA), administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks) were treated with taurine (100 mg/kg, i.p., once daily), monoisoamyl dimercaptosuccinic acid (MiADMSA) (50 mg/kg, oral, once daily) either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood delta-aminolevulinic acid dehydratase (ALAD) activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP) level. Clinical hematological variables like white blood cells (WBC), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) showed significant decrease with a significant elevation in platelet (PLT) count. These changes were accompanied by significant decrease in superoxide dismutase (SOD) activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH) level and an increase in oxidized glutathione (GSSG). These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co

  5. Effect of taurine supplementation on the alterations in amino Acid content in skeletal muscle with exercise in rat.

    PubMed

    Ishikura, Keisuke; Miyazaki, Teruo; Ra, Song-Gyu; Endo, Shoji; Nakamura, Yusuke; Matsuzaka, Takashi; Miyakawa, Shumpei; Ohmori, Hajime

    2011-01-01

    Taurine included abundantly in skeletal muscle, particularly in the slow-twitch fibers, enhances exercise performance. However, the exact mechanisms for this effect have been unclear. The present study investigated the influence of taurine supplementation on amino acids profile in skeletal muscles as one of mechanisms in the enhancement of exercise performance induced by taurine. In the rats that received taurine solution, amino acids concentrations were comprehensively quantified in two portions with different fiber compositions in the fast-twitch fiber dominant (FFD) gastrocnemius muscle after 2 weeks, and in the gastrocnemius and additional other FFD muscles, liver, and plasma with exhausted exercise after 3 weeks. In the FFD muscles after 2 weeks, a common phenomenon that decreased concentrations of threonine (-16%), serine (-15~-16%), and glycine (-6~-16%) were observed, and they are categorized in the pyruvate precursors for hepatic gluconeogenesis rather than biosynthesis, polar, and side-chain structures. The decreases in the three amino acids were significantly emphasized after an additional week of taurine supplementation in the FFD muscles (p values in three amino acids in these tissues were less than 0.001-0.05), but not in the liver and plasma, accompanied with significantly increase of running time to exhaustion (p <0.05). In contrast, the three amino acids (threonine and serine; p < 0.05, glycine; p < 0.01) and alanine (p < 0.01) in the liver were significantly decreased and increased, respectively, following the exhaustive exercise. In conclusion, the taurine-induced reductions of these amino acids in skeletal muscle might be one of the mechanisms which underpin the enhancement of exercise performance by taurine. Key pointsTaurine ingestion significantly decreased certain amino acids in skeletal muscles accompanied with enhanced exercise performance.The decreased amino acids in common were threonine, serine, and glycine, but not alanine; pyruvate

  6. Raman spectra of deuteriated taurine single crystals

    NASA Astrophysics Data System (ADS)

    Souza, J. M. de; Lima, R. J. C.; Freire, P. T. C.; Sasaki, J. M.; Melo, F. E. A.; Filho, J. Mendes; Jones, Derry W.

    2005-05-01

    The polarized Raman spectra of partially deuteriated taurine [(ND 3+) 0.65(NH 3+) 0.35(CH 2) 2SO 3-] crystals from x( zz) x and x( zy) x scattering geometries of the A g and B g irreducible representations of the factor group C 2h are reported. The temperature-dependent Raman spectra of partially deuteriated taurine do not reveal any evidence of the structural phase transition undergone by normal taurine at about 250 K, but an anomaly observed in the 180 cm -1 band at ˜120 K implies a different dynamic for this band (which is involved in a pressure-induced phase transition) in the deuteriated crystal.

  7. Neuroprotective Mechanisms of Taurine against Ischemic Stroke

    PubMed Central

    Menzie, Janet; Prentice, Howard; Wu, Jang-Yen

    2013-01-01

    Ischemic stroke exhibits a multiplicity of pathophysiological mechanisms. To address the diverse pathophysiological mechanisms observed in ischemic stroke investigators seek to find therapeutic strategies that are multifaceted in their action by either investigating multipotential compounds or by using a combination of compounds. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions. It exhibits antioxidative properties, stabilizes membrane, functions as an osmoregulator, modulates ionic movements, reduces the level of pro-inflammators, regulates intracellular calcium concentration; all of which contributes to its neuroprotective effect. Data are accumulating that show the neuroprotective mechanisms of taurine against stroke pathophysiology. In this review, we describe the neuroprotective mechanisms employed by taurine against ischemic stroke and its use in clinical trial for ischemic stroke. PMID:24961429

  8. Taurine Inhibits K+-Cl− Cotransporter KCC2 to Regulate Embryonic Cl− Homeostasis via With-no-lysine (WNK) Protein Kinase Signaling Pathway*

    PubMed Central

    Inoue, Koichi; Furukawa, Tomonori; Kumada, Tatsuro; Yamada, Junko; Wang, Tianying; Inoue, Rieko; Fukuda, Atsuo

    2012-01-01

    GABA inhibits mature neurons and conversely excites immature neurons due to lower K+-Cl− cotransporter 2 (KCC2) expression. We observed that ectopically expressed KCC2 in embryonic cerebral cortices was not active; however, KCC2 functioned in newborns. In vitro studies revealed that taurine increased KCC2 inactivation in a phosphorylation-dependent manner. When Thr-906 and Thr-1007 residues in KCC2 were substituted with Ala (KCC2T906A/T1007A), KCC2 activity was facilitated, and the inhibitory effect of taurine was not observed. Exogenous taurine activated the with-no-lysine protein kinase 1 (WNK1) and downstream STE20/SPS1-related proline/alanine-rich kinase (SPAK)/oxidative stress response 1 (OSR1), and overexpression of active WNK1 resulted in KCC2 inhibition in the absence of taurine. Phosphorylation of SPAK was consistently higher in embryonic brains compared with that of neonatal brains and down-regulated by a taurine transporter inhibitor in vivo. Furthermore, cerebral radial migration was perturbed by a taurine-insensitive form of KCC2, KCC2T906A/T1007A, which may be regulated by WNK-SPAK/OSR1 signaling. Thus, taurine and WNK-SPAK/OSR1 signaling may contribute to embryonic neuronal Cl− homeostasis, which is required for normal brain development. PMID:22544747

  9. The nuclear receptor FXR regulates hepatic transport and metabolism of glutamine and glutamate.

    PubMed

    Renga, Barbara; Mencarelli, Andrea; Cipriani, Sabrina; D'Amore, Claudio; Zampella, Angela; Monti, Maria Chiara; Distrutti, Eleonora; Fiorucci, Stefano

    2011-11-01

    Hepatic transport and metabolism of glutamate and glutamine are regulated by intervention of several proteins. Glutamine is taken up by periportal hepatocytes and is the major source of ammonia for urea synthesis and glutamate for N-acetylglutamate (NAG) synthesis, which is catalyzed by the N-acetylglutamate synthase (NAGS). Glutamate is taken up by perivenous hepatocytes and is the main source for the synthesis of glutamine, catalyzed by glutamine synthase (GS). Accumulation of glutamate and ammonia is a common feature of chronic liver failure, but mechanism that leads to failure of the urea cycle in this setting is unknown. The Farnesoid X Receptor (FXR) is a bile acid sensor in hepatocytes. Here, we have investigated its role in the regulation of the metabolism of both glutamine and glutamate. In vitro studies in primary cultures of hepatocytes from wild type and FXR(-/-) mice and HepG2 cells, and in vivo studies, in FXR(-/-) mice as well as in a rodent model of hepatic liver failure induced by carbon tetrachloride (CCl(4)), demonstrate a role for FXR in regulating this metabolism. Further on, promoter analysis studies demonstrate that both human and mouse NAGS promoters contain a putative FXRE, an ER8 sequence. EMSA, ChIP and luciferase experiments carried out to investigate the functionality of this sequence demonstrate that FXR is essential to induce the expression of NAGS. In conclusion, FXR activation regulates glutamine and glutamate metabolism and FXR ligands might have utility in the treatment of hyperammonemia states. PMID:21757002

  10. Host defense--a role for the amino acid taurine?

    PubMed

    Stapleton, P P; O'Flaherty, L; Redmond, H P; Bouchier-Hayes, D J

    1998-01-01

    Taurine (2-aminoethane sulphonic acid), a ubiquitous beta-amino acid is conditionally essential in man. It is not utilized in protein synthesis but found free or in some simple peptides. Derived from methionine and cysteine metabolism, taurine is known to play a pivotal role in numerous physiological functions. Some of the roles with which taurine has been associated include osmoregulation, antioxidation, detoxification and stimulation of glycolysis and glycogenesis. Intracellular taurine is maintained at high concentrations in a variety of cell types and alteration of cell taurine levels is difficult. The role of taurine within the cell appears to be determined by the cell type. Recent research has determined a regulatory role for taurinechloramine, the product formed by the reaction between taurine and neutrophil derived hypochlorous acid on macrophage function. Plasma taurine levels are also high, although decreases are observed in response to surgical injury and numerous pathological conditions including cancer and sepsis. Supplementary taurine replenishes decreased plasma taurine. Although commonly used as a dietary supplement in the Far East, the potential advantages of dietary taurine supplementation have not as yet been fully recognized in the Western World; this is an area which could prove to be beneficial in the clinical arena. PMID:9437654

  11. Interaction of sirolimus and everolimus with hepatic and intestinal organic anion-transporting polypeptide transporters.

    PubMed

    Picard, Nicolas; Levoir, Laure; Lamoureux, Fabien; Yee, Sook Wah; Giacomini, Kathleen M; Marquet, Pierre

    2011-09-01

    The goal of this study was to assess the interaction of the mTOR inhibitors (ImTORs) sirolimus and everolimus with the human organic anion-transporting polypeptides (OATPs) expressed in hepatocytes and enterocytes by conducting uptake experiments using (i) transfected HEK293T cells, (ii) the hepatocyte-like HepaRG cell line and (iii) the enterocyte-like Caco-2 cell line. Sirolimus and everolimus inhibited in a dose-dependent manner the uptake of [³H]-estrone sulphate by OATP1A2 and OATP1B1 and that of mycophenolic acid 7-O-glucuronide (MPAG) by OATP1B3. ImTOR apparent 50% inhibitory concentrations (IC₅₀) for OATPs were 11.9 µM (OATP1A2), 9.8 µM (OATP1B1) and 1.3 µM (OATP1B3) for sirolimus and 4.2 µM (OATP1A2), 4.1 µM (OATP1B1) and 4.3 µM (OATP1B3) for everolimus. No transport of sirolimus or everolimus by OATP1A2, OATP1B1 or OATP1B3 was observed in HEK-transfected cells and the OAT/OATP/MRP chemical inhibitor probenecid did not significantly decrease the uptake of sirolimus and everolimus in HepaRG and Caco-2 cells, but tended to increase their intracellular accumulation presumably through efflux inhibition. In conclusion, our data suggest that the major OATP transporters expressed in the liver and the intestine do not contribute to the pharmacokinetics of sirolimus and everolimus. However, ImTORs are inhibitors of these transporters. PMID:21524191

  12. Gene Expression Variability in Human Hepatic Drug Metabolizing Enzymes and Transporters

    PubMed Central

    Yang, Lun; Price, Elvin T.; Chang, Ching-Wei; Li, Yan; Huang, Ying; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang

    2013-01-01

    Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications. PMID:23637747

  13. Review: Taurine: A “very essential” amino acid

    PubMed Central

    Shen, Wen

    2012-01-01

    Taurine is an organic osmolyte involved in cell volume regulation, and provides a substrate for the formation of bile salts. It plays a role in the modulation of intracellular free calcium concentration, and although it is one of the few amino acids not incorporated into proteins, taurine is one of the most abundant amino acids in the brain, retina, muscle tissue, and organs throughout the body. Taurine serves a wide variety of functions in the central nervous system, from development to cytoprotection, and taurine deficiency is associated with cardiomyopathy, renal dysfunction, developmental abnormalities, and severe damage to retinal neurons. All ocular tissues contain taurine, and quantitative analysis of ocular tissue extracts of the rat eye revealed that taurine was the most abundant amino acid in the retina, vitreous, lens, cornea, iris, and ciliary body. In the retina, taurine is critical for photoreceptor development and acts as a cytoprotectant against stress-related neuronal damage and other pathological conditions. Despite its many functional properties, however, the cellular and biochemical mechanisms mediating the actions of taurine are not fully known. Nevertheless, considering its broad distribution, its many cytoprotective attributes, and its functional significance in cell development, nutrition, and survival, taurine is undoubtedly one of the most essential substances in the body. Interestingly, taurine satisfies many of the criteria considered essential for inclusion in the inventory of neurotransmitters, but evidence of a taurine-specific receptor has yet to be identified in the vertebrate nervous system. In this report, we present a broad overview of the functional properties of taurine, some of the consequences of taurine deficiency, and the results of studies in animal models suggesting that taurine may play a therapeutic role in the management of epilepsy and diabetes. PMID:23170060

  14. Calcium channel blockers ameliorate iron overload-associated hepatic fibrosis by altering iron transport and stellate cell apoptosis.

    PubMed

    Zhang, Ying; Zhao, Xin; Chang, Yanzhong; Zhang, Yuanyuan; Chu, Xi; Zhang, Xuan; Liu, Zhenyi; Guo, Hui; Wang, Na; Gao, Yonggang; Zhang, Jianping; Chu, Li

    2016-06-15

    Liver fibrosis is the principal cause of morbidity and mortality in patients with iron overload. Calcium channel blockers (CCBs) can antagonize divalent cation entry into renal and myocardial cells and inhibit fibrogenic gene expression. We investigated the potential of CCBs to resolve iron overload-associated hepatic fibrosis. Kunming mice were assigned to nine groups (n=8 per group): control, iron overload, deferoxamine, high and low dose verapamil, high and low dose nimodipine, and high and low dose diltiazem. Iron deposition and hepatic fibrosis were measured in mouse livers. Expression levels of molecules associated with transmembrane iron transport were determined by molecular biology approaches. In vitro HSC-T6 cells were randomized into nine groups (the same groups as the mice). Changes in proliferation, apoptosis, and metalloproteinase expression in cells were detected to assess the anti-fibrotic effects of CCBs during iron overload conditions. We found that CCBs reduced hepatic iron content, intracellular iron deposition, the number of hepatic fibrotic areas, collagen expression levels, and hydroxyproline content. CCBs rescued abnormal expression of α1C protein in L-type voltage-dependent calcium channel (LVDCC) and down-regulated divalent metal transporter-1 (DMT-1) expression in mouse livers. In iron-overloaded HSC-T6 cells, CCBs reduced iron deposition, inhibited proliferation, induced apoptosis, and elevated expression of matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1). CCBs are potential therapeutic agents that can be used to address hepatic fibrosis during iron overload. They resolve hepatic fibrosis probably correlated with regulating transmembrane iron transport and inhibiting HSC growth. PMID:27095094

  15. The protective effects of taurine on acute ammonia toxicity in grass carp Ctenopharynodon idellus.

    PubMed

    Xing, Xiaodan; Li, Ming; Yuan, Lixia; Song, Meize; Ren, Qianyan; Shi, Ge; Meng, Fanxing; Wang, Rixin

    2016-09-01

    The four experimental groups were carried out to test the response of grass carp Ctenopharyngodon idella to ammonia toxicity and taurine: group 1 was injected with NaCl, group 2 was injected with ammonium acetate, group 3 was injected with ammonium acetate and taurine, and group 4 was injected taurine. Fish in group 2 had the highest ammonia content in the liver and brain, and alanine, arginine, glutamine, glutamate and glycine contents in liver. Brain alanine and glutamate of fish in group 2 were significantly higher than those of fish in group 1. Malondialdehyde content of fish in group 2 was the highest, but superoxide dismutase and glutathione activities were the lowest. Although fish in group 2 had the lowest red cell count and hemoglobin, the highest alkaline phosphatase, complement C3, C4 and total immunoglobulin contents appeared in this group. In addition, superoxide dismutase and glutathione activities, red cell count and hemoglobin of fish in group 3 were significantly higher than those of fish in group 2, but malondialdehyde content is the opposite. This study indicates that ammonia exerts its toxic effects by interfering with amino acid transport, inducing reactive oxygen species generation and malondialdehyde accumulation, leading to blood deterioration and over-activation of immune response. The exogenous taurine could mitigate the adverse effect of high ammonia level on fish physiological disorder. PMID:27514785

  16. Niemann-Pick C1-Like 1 (NPC1L1) Protein in Intestinal and Hepatic Cholesterol Transport

    PubMed Central

    Jia, Lin; Betters, Jenna L.; Yu, Liqing

    2014-01-01

    Increased blood cholesterol is an independent risk factor for atherosclerotic cardiovascular disease. Cholesterol homeostasis in the body is controlled mainly by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann-Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It functions as a sterol transporter to mediate intestinal cholesterol absorption and counterbalances hepatobiliary cholesterol excretion. NPC1L1 is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that is widely used in treating hypercholesterolemia. Recent findings suggest that NPC1L1 deficiency or ezetimibe treatment also prevents diet-induced hepatic steatosis and obesity in addition to reducing blood cholesterol. Future studies should focus on molecular mechanisms underlying NPC1L1-dependent cholesterol transport and elucidation of how a cholesterol transporter modulates the pathogenesis of metabolic diseases. PMID:20809793

  17. Effect of taurine on platelets and the plasma coagulation system.

    PubMed

    Miglis, Mitchell; Wilder, Donna; Reid, Thomas; Bakaltcheva, Irina

    2002-02-01

    It is not yet clear what exact mechanisms are at work in hibernating animals that prevent clot formation and maintain tissue perfusion under conditions of very slow blood flow and increased blood viscosity brought about by the low temperatures. It has been shown that the total amino acid pool increases more then two fold in hibernating animals with taurine accounting for about 50% of this increase [Storey et al., Proc Natl Acad Sci USA 1988; 85(21): 8350-4]. This work investigates the effect of taurine on platelets and the plasma coagulation system. Taurine was added at different concentrations in the range between 5 and 25 mM to donor plasma. Using STA/STA Compact coagulation analyzer the following tests were performed: prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). At the highest concentration tested (25 mM) taurine prolonged TT by 9%. The prolongation was statistically significant but not clinically significant retaining TT within normal limits (16.7-20.7 s). PT and APTT remained unchanged by taurine. The effect of taurine on platelets was assessed by platelet aggregation by thrombin, extent of platelet shape change (ESC) induced by ADP, and thrombelastography. Taurine at 5 mM final concentration inhibited platelet aggregation by 10%. Increasing taurine concentration to 25 mM did not result in a further augmentation of the inhibitory effect. ESC was unaffected by taurine. Clot strength determined by thrombelastography also remained unchanged by taurine. PMID:11918831

  18. Role of taurine in the pathogenesis of obesity.

    PubMed

    Murakami, Shigeru

    2015-07-01

    Taurine is a sulfur-containing amino acid that is present in mammalian tissues in millimolar concentrations. Taurine is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation. The prevalence of obesity and being overweight continues to rise worldwide at an alarming rate. Obesity is associated with a higher risk of metabolic and cardiovascular diseases, cancer, and other clinical conditions. Ingestion of taurine has been shown to alleviate metabolic diseases such as hyperlipidemia, diabetes, hypertension, and obesity in animal models. A global epidemiological survey showed that 24-h urinary taurine excretion, as a marker of dietary taurine intake, was inversely associated with BMI, blood pressure, and plasma cholesterol in humans. In addition, taurine chloramine, an endogenous product derived from activated neutrophils, has been reported to suppress obesity-induced oxidative stress and inflammation in adipocytes. Synthetic activity and concentration of taurine in adipose tissues and plasma have been shown to decrease in humans and animals during the development of obesity, suggesting a relationship between taurine deficiency and obesity. In this review, I summarize the effects of taurine on the progression of obesity in animal models and humans. Furthermore, I discuss possible mechanisms underlying the antiobesity effects of taurine. PMID:25787113

  19. Taurine provides neuroprotection against retinal ganglion cell degeneration.

    PubMed

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  20. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    PubMed Central

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  1. Endotoxin-Mediated Downregulation of Hepatic Drug Transporters in HIV-1 Transgenic Rats.

    PubMed

    Ghoneim, Ragia H; Piquette-Miller, Micheline

    2016-05-01

    Altered expression of drug transporters and metabolic enzymes is known to occur in infection-induced inflammation. We hypothesize that in human immunodeficiency virus (HIV)-infected individuals, further alteration could occur as a result of augmented inflammation. The HIV-1 transgenic (Tg) rat is used to simulate HIV pathologies associated with the presence of HIV viral proteins. Therefore, the objective of this study was to examine the effect of endotoxin administration on the gene expression of drug transporters in the liver of HIV-Tg rats. Male and female HIV-Tg and wild-type (WT) littermates were injected with 5 mg/kg endotoxin or saline (n= 7-9/group). Eighteen hours later, rats were euthanized and tissues were collected. Quantitative real-time polymerase chain reaction and Western blot analysis were used to measure hepatic gene and protein expression, respectively, and enzyme-linked immunosorbent assay was used to measure serum cytokine levels. Although an augmented inflammatory response was seen in HIV-Tg rats, similar endotoxin- mediated downregulation of Abcb1a, Abcc2, Abcg2, Abcb11, Slco1a1, Slco1a2, Slco1b2, Slc10a1, Slc22a1, Cyp3a2, and Cyp3a9 gene expression was seen in the HIV-Tg and WT groups. A significantly greater endotoxin- mediated downregulation of Ent1/Slc29a1 was seen in female HIV-Tg rats. Basal expression of inflammatory mediators was not altered in the HIV-Tg rat; likewise, the basal expression of most transporters was not significantly different between HIV-Tg and WT rats. Our findings suggest that hepatobiliary clearances of endogenous and exogenous substrates are altered in the HIV-Tg rat after endotoxin exposure. This is of particular importance because HIV-infected individuals frequently present with bacterial or viral infections, which are a potential source for drug-disease interactions. PMID:26977098

  2. Preventive effect of taurine on experimental type II diabetic nephropathy

    PubMed Central

    2010-01-01

    Background It has been verified that taurine has some preventive effects on diabetes and its complications when used alone or together with other drugs, but there are few reports about taurine on the prevention of diabetic nephropathy, the mechanisms of which are still unknown. Methods Taurine was administered to type Ⅱ diabetic rats induced by high fat high sugar diet combined with STZ injection. The preventive effect of taurine on diabetic nephropathy was investigated by detecting blood glucose, lipid metabolism, kidney function and glomerular basement membrane metabolism. Results Taurine could lower blood glucose, TG, TC, BUN, Scr, NAG, U-PRO, the expression of laminin B1( LBN1) mRNA, and increase HDL-C of diabetic rats. Conclusions The results indicated that taurine could prevent the occurrence and development of diabetic nephropathy by decreasing blood glucose, improving lipid metabolism, glomerular basement membrane metabolism, and kidney function. PMID:20804623

  3. 33S NMR cryogenic probe for taurine detection

    NASA Astrophysics Data System (ADS)

    Hobo, Fumio; Takahashi, Masato; Maeda, Hideaki

    2009-03-01

    With the goal of a S33 nuclear magnetic resonance (NMR) probe applicable to in vivo NMR on taurine-biological samples, we have developed the S33 NMR cryogenic probe, which is applicable to taurine solutions. The NMR sensitivity gain relative to a conventional broadband probe is as large as 3.5. This work suggests that improvements in the preamplifier could allow NMR measurements on 100 μM taurine solutions, which is the level of sensitivity necessary for biological samples.

  4. OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin

    PubMed Central

    Chen, Ligong; Shu, Yan; Liang, Xiaomin; Chen, Eugene C.; Yee, Sook Wah; Zur, Arik A.; Li, Shuanglian; Xu, Lu; Keshari, Kayvan R.; Lin, Michael J.; Chien, Huan-Chieh; Zhang, Youcai; Morrissey, Kari M.; Liu, Jason; Ostrem, Jonathan; Younger, Noah S.; Kurhanewicz, John; Shokat, Kevan M.; Ashrafi, Kaveh; Giacomini, Kathleen M.

    2014-01-01

    Organic cation transporter 1, OCT1 (SLC22A1), is the major hepatic uptake transporter for metformin, the most prescribed antidiabetic drug. However, its endogenous role is poorly understood. Here we show that similar to metformin treatment, loss of Oct1 caused an increase in the ratio of AMP to ATP, activated the energy sensor AMP-activated kinase (AMPK), and substantially reduced triglyceride (TG) levels in livers from healthy and leptin-deficient mice. Conversely, livers of human OCT1 transgenic mice fed high-fat diets were enlarged with high TG levels. Metabolomic and isotopic uptake methods identified thiamine as a principal endogenous substrate of OCT1. Thiamine deficiency enhanced the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase. Metformin and the biguanide analog, phenformin, competitively inhibited OCT1-mediated thiamine uptake. Acute administration of metformin to wild-type mice reduced intestinal accumulation of thiamine. These findings suggest that OCT1 plays a role in hepatic steatosis through modulation of energy status. The studies implicate OCT1 as well as metformin in thiamine disposition, suggesting an intriguing and parallel mechanism for metformin and its major hepatic transporter in metabolic function. PMID:24961373

  5. Effect of cadmium on calcium transport in a human fetal hepatic cell line (WRL-68 cells).

    PubMed

    Souza, V; Bucio, L; Jay, D; Chávez, E; Gutiérrez-Ruiz, M C

    1996-08-16

    Toxic metals appear to use the transport pathways that exist for biologically essential metals. Calcium uptake in cells occurs through specific membrane channels. Since cadmium inhibits calcium uptake, this study was carried on to elucidate the mechanism of Cd interference with calcium transport using the fetal hepatic cell line WRL-68 as an in vitro model. Ca accumulation by WRL-68 cells presented an initial rapid phase, followed by a sustained phase of slower accumulation over a 60 min period. A concentration of 50 microM CdCl2 produced 39% inhibition of the uptake of CaCl2 (100 microM), while 100 microM nifedipine or verapamil decreased Ca accumulation by 35 and 63%, respectively. All Cd concentrations tested produced significant decrease in Ca uptake in a concentration-dependent manner at 1 min and thereafter, although with 10 microM CdCl2 no significant difference was found after 30 min of incubation. From the Lineweaver-Burk plot, we found that Cd exerted a competitive inhibition on Ca uptake, since there was no significant effect on the Vmax but an increased K(m). A second order rate constant of Cd inactivation of 0.061 mM-1.s-1 was determined from the course of Ca uptake during Cd inhibition. SH groups seemed to play an essential role in Ca inhibition uptake by Cd because the inhibition of Ca accumulation by 50 microM Cd was practically reversed after the addition of dithiothreitol. PMID:8814339

  6. Regulation of Hepatic Cholesteryl Ester Transfer Protein Expression and Reverse Cholesterol Transport by Inhibition of DNA Topoisomerase II*

    PubMed Central

    Liu, Mengyang; Chen, Yuanli; Zhang, Ling; Wang, Qixue; Ma, Xingzhe; Li, Xiaoju; Xiang, Rong; Zhu, Yan; Qin, Shucun; Yu, Yang; Jiang, Xian-cheng; Duan, Yajun; Han, Jihong

    2015-01-01

    Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from high density lipoprotein to triglyceride-rich lipoproteins. CETP expression can be transcriptionally activated by liver X receptor (LXR). Etoposide and teniposide are DNA topoisomerase II (Topo II) inhibitors. Etoposide has been reported to inhibit atherosclerosis in rabbits with un-fully elucidated mechanisms. In this study we determined if Topo II activity can influence cholesterol metabolism by regulating hepatic CETP expression. Inhibition of Topo II by etoposide, teniposide, or Topo II siRNA increased CETP expression in human hepatic cell line, HepG2 cells, which was associated with increased CETP secretion and mRNA expression. Meanwhile, inhibition of LXR expression by LXR siRNA attenuated induction of CETP expression by etoposide and teniposide. Etoposide and teniposide induced LXRα expression and LXRα/β nuclear translocation while inhibiting expression of receptor interacting protein 140 (RIP140), an LXR co-repressor. In vivo, administration of teniposide moderately reduced serum lipid profiles, induced CETP expression in the liver, and activated reverse cholesterol transport in CETP transgenic mice. Our study demonstrates a novel function of Topo II inhibitors in cholesterol metabolism by activating hepatic CETP expression and reverse cholesterol transport. PMID:25914138

  7. Inhibitory effect of taurine on veratridine-evoked D-[3H]aspartate release from murine corticostriatal slices: involvement of chloride channels and mitochondria.

    PubMed

    Molchanova, Svetlana M; Oja, Simo S; Saransaari, Pirjo

    2007-01-26

    We have previously shown that the inhibitory neuromodulator taurine attenuates the release of preloaded D-[3H]aspartate from murine corticostriatal slices evoked by ischemic conditions or by application of the sodium channel agonist veratridine. The release of D-[3H]aspartate (a non-metabolized analog of glutamate) was used as an index of glutamate release. The aim of the present study was to reveal the molecular mechanisms responsible for this inhibitory effect of taurine. It was shown that 10 mM taurine suppresses D-[3H]aspartate release evoked by 0.1 mM veratridine, but does not affect the high-K+ -(50 mM) or ouabain- (0.1 mM) evoked release. Taurine had no effect in Ca2+ -free medium when the synaptic exocytosis of D-[3H]aspartate was inhibited. Nor did it suppress the release from slices preloaded with the competitive glutamate uptake blocker DL-threo-beta-hydroxyaspartate (THBA), which inhibits D-[3H]aspartate release mediated by the reverse action of glutamate transporters. Omission of Cl- from the incubation medium reduced the effect of taurine, signifying the involvement of a Cl- channel. The glycine receptor antagonist strychnine and the GABA(A) receptor antagonist bicuculline did not block the taurine effect, although picrotoxin, a less specific blocker of agonist-gated chloride channels, completely prevented the effect of taurine on veratridine-induced D-[3H]aspartate release. The respiratory chain blocker rotenone or mitochondrial protonophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP) in combination with the mitochondrial ATPase inhibitor oligomycin, which inhibits the mitochondrial Ca2+ uniporter, also reduced the effect of taurine. The results obtained in the present study show that taurine acts specifically on the release of preloaded D-[3H]aspartate evoked by veratridine, but not on that evoked by other depolarizing agents, and affects the release mediated both by synaptic exocytosis and the reverse action of glutamate transporter. Taurine

  8. Proteomic Analysis of the Developmental Trajectory of Human Hepatic Membrane Transporter Proteins in the First Three Months of Life.

    PubMed

    Mooij, Miriam G; van de Steeg, Evita; van Rosmalen, Joost; Windster, Jonathan D; de Koning, Barbara A E; Vaes, Wouter H J; van Groen, Bianca D; Tibboel, Dick; Wortelboer, Heleen M; de Wildt, Saskia N

    2016-07-01

    Human hepatic membrane-embedded transporter proteins are involved in trafficking endogenous and exogenous substrates. Even though impact of transporters on pharmacokinetics is recognized, little is known on maturation of transporter protein expression levels, especially during early life. We aimed to study the protein expression of 10 transporters in liver tissue from fetuses, infants, and adults. Transporter protein expression levels [ATP-binding cassette transporter (ABC)B1, ABCG2, ABCC2, ABCC3, bile salt efflux pump, glucose transporter 1, monocarboxylate transporter 1, organic anion transporter polypeptide (OATP)1B1, OATP2B1, and organic cation/carnitine transporter 2) were quantified using ultraperformance liquid chromatography tandem mass spectrometry in snap-frozen postmortem fetal, infant, and adult liver samples. Protein expression was quantified in isolated crude membrane fractions. The possible association between postnatal and postmenstrual age versus protein expression was studied. We studied 25 liver samples, as follows: 10 fetal [median gestational age 23.2 wk (range 16.4-37.9)], 12 infantile [gestational age at birth 35.1 wk (27.1-41.0), postnatal age 1 wk (0-11.4)], and 3 adult. The relationship of protein expression with age was explored by comparing age groups. Correlating age within the fetal/infant age group suggested four specific protein expression patterns, as follows: stable, low to high, high to low, and low-high-low. The impact of growth and development on human membrane transporter protein expression is transporter-dependent. The suggested age-related differences in transporter protein expression may aid our understanding of normal growth and development, and also may impact the disposition of substrate drugs in neonates and young infants. PMID:27103634

  9. Role of hepatic lipase and endothelial lipase in high-density lipoprotein-mediated reverse cholesterol transport.

    PubMed

    Annema, Wijtske; Tietge, Uwe J F

    2011-06-01

    Reverse cholesterol transport (RCT) constitutes a key part of the atheroprotective properties of high-density lipoproteins (HDL). Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol levels. Although overexpression of EL decreases overall macrophage-to-feces RCT, knockout of both HL and EL leaves RCT essentially unaffected. With respect to important individual steps of RCT, current data on the role of EL and HL in cholesterol efflux are not conclusive. Both enzymes increase hepatic selective cholesterol uptake; however, this does not translate into altered biliary cholesterol secretion, which is regarded the final step of RCT. Also, the impact of HL and EL on atherosclerosis is not clear cut; rather it depends on respective experimental conditions and chosen models. More mechanistic insights into the diverse biological properties of these enzymes are therefore required to firmly establish EL and HL as targets for the treatment of atherosclerotic cardiovascular disease. PMID:21424685

  10. Taurine in the osmoregulation of the Brattleboro rat

    SciTech Connect

    Nieminen, M.J.; Tuomisto, L.; Solatunturi, E.; Eriksson, L.; Paasonen, M.K.

    1988-01-01

    The function of taurine in mammalian osmoregulation was studied in the Brattleboro rat with hereditary hypothalamic diabetes insipidus (DI). DI rats are chronically dehydrated because of their inability to synthesize vasopressin. One day of water deprivation did not affect the water balance in rats with normal vasopressin synthesis, whereas DI rats were markedly dehydrated and lost considerably body weight. Taurine content and /sup 3/H-taurine accumulation by platelets were significantly higher in DI rats, with a further increase after one day of water deprivation. In DI rats, water deprivation also evoked a clear taurine increase in skeletal muscle and in the brain. These findings indicate that taurine has an osmoregulatory function in mammals.

  11. Taurine activates GABAergic networks in the neocortex of immature mice

    PubMed Central

    Sava, Bogdan A.; Chen, Rongqing; Sun, Haiyan; Luhmann, Heiko J.; Kilb, Werner

    2014-01-01

    Although it has been suggested that taurine is the main endogenous neurotransmitter acting on glycine receptors, the implications of glycine receptor-mediated taurine actions on immature neocortical networks have not been addressed yet. To investigate the influence of taurine on the excitability of neuronal networks in the immature neocortex, we performed whole-cell patch-clamp recordings from visually identified pyramidal neurons and interneurons in coronal slices from C57Bl/6 and GAD67-green fluorescent protein (GFP) transgenic mice (postnatal days 2–4). In 46% of the pyramidal neurons bath-application of taurine at concentrations ≥ 300 μM significantly enhanced the frequency of postsynaptic currents (PSCs) by 744.3 ± 93.8% (n = 120 cells). This taurine-induced increase of PSC frequency was abolished by 0.2 μM tetrodotoxin (TTX), 1 μM strychnine or 3 μM gabazine, but was unaffected by the glutamatergic antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (±) R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP), suggesting that taurine specifically activates GABAergic network activity projecting to pyramidal neurons. Cell-attached recordings revealed that taurine enhanced the frequency of action potentials (APs) in pyramidal neurons, indicating an excitatory action of the GABAergic PSCs. In order to identify the presynaptic targets of taurine we demonstrate that bath application of taurine induced in GAD67-GFP labeled interneurons an inward current that is mainly mediated by glycine receptors and can generate APs in these cells. We conclude from these results that taurine can enhance network excitability in the immature neocortex by selectively activating GABAergic interneurons via interactions with glycine receptors. PMID:24550782

  12. Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice.

    PubMed

    Vasandani, Chandna; Kafrouni, Abdallah I; Caronna, Antonella; Bashmakov, Yuriy; Gotthardt, Michael; Horton, Jay D; Spady, David K

    2002-05-01

    We determined the effects of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on parameters of plasma lipoprotein and hepatic lipid metabolism in LDL receptor (LDLr) knockout mice. Dietary n-3 PUFA decreased the rate of appearance and increased the hepatic clearance of IDL/LDL resulting in a marked decrease in the plasma concentration of these particles. Dietary n-3 PUFA increased the hepatic clearance of IDL/LDL through a mechanism that appears to involve apolipoprotein (apo)E but is independent of the LDLr, the LDLr related protein (LRP), the scavenger receptor B1, and the VLDLr. The decreased rate of appearance of IDL/VLDL in the plasma of animals fed n-3 PUFA could be attributed to a marked decrease in the plasma concentration of precursor VLDL. Decreased plasma VLDL concentrations were due in part to decreased hepatic secretion of VLDL triglyceride and cholesteryl esters, which in turn was associated with decreased concentrations of these lipids in liver. Decreased hepatic triglyceride concentrations in animals fed n-3 PUFA were due in part to suppression of fatty acid synthesis as a result of a decrease in sterol regulatory element binding protein-1 (SREBP-1) expression and processing. In conclusion, these studies indicate that n-3 PUFA can markedly decrease the plasma concentration of apoB-containing lipoproteins and enhance hepatic LDL clearance through a mechanism that does not involve the LDLr pathway or LRP. PMID:11971949

  13. Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs): Influence of Protein Expression on Drug–Drug Interactions

    PubMed Central

    2012-01-01

    The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug–drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors. PMID:22541068

  14. Involvement of organic anion-transporting polypeptides in the hepatic uptake of dioscin in rats and humans.

    PubMed

    Zhang, Aijie; Wang, Changyuan; Liu, Qi; Meng, Qiang; Peng, Jinyong; Sun, Huijun; Ma, Xiaochi; Huo, Xiaokui; Liu, Kexin

    2013-05-01

    The objective of this study was to clarify the mechanism underlying hepatic uptake of dioscin (diosgenyl 2,4-di-O-a-L-rhamnopyranosyl-p-D-glucopyranoside), an herbal ingredient with antihepatitis activity, in rats and humans. The liver uptake index (LUI) in vivo, perfused rat liver in situ, rat liver slices, isolated rat hepatocytes, and human organic anion-transporting polypeptide (OATP)-transfected cells in vitro were used to evaluate hepatic uptake of dioscin. Values of 11.9% ± 1.6% and 15.0% ± 0.9% of dose for uptake of dioscin were observed by LUI in vivo and perfused rat livers in situ, respectively. The time course of dioscin uptake by rat liver slices was temperature-dependent. Uptake of dioscin by rat liver slices and isolated rat hepatocytes was inhibited significantly by Oatp modulators, such as ibuprofen (Oatp1a1 inhibitor), digoxin (Oatp1a4 substrate), and glycyrrhizic acid (Oatp1b2 inhibitor), but not by TEA or p-aminohippurate. Uptake of dioscin in rat hepatocytes and OATP1B3-human embryonic kidney (HEK) 293 cells indicated a saturable process with a Km of 3.75 ± 0.51 μM and 2.08 ± 0.27 μM, respectively. (-)-Epigallocatechin gallate, cyclosporin A, rifampicin, and telmisartan inhibited transport of dioscin in OATP1B3-HEK293 cells. However, transcellular transport of dioscin in OATP1B1- or OATP1B1/multidrug resistance-associated protein 2-Madin-Darby canine kidney strain II cells was not observed. These results indicate that hepatic uptake of dioscin is involved in OATP1B3 in humans, and multiple Oatps might participate in this process in rats. PMID:23396419

  15. Effects of taurine on human embryo development in vitro.

    PubMed

    Devreker, F; Van den Bergh, M; Biramane, J; Winston, R L; Englert, Y; Hardy, K

    1999-09-01

    Glutamine and taurine are reported to be beneficial for mouse embryo development in vitro, and we have recently shown that glutamine improves human blastocyst formation in vitro. This randomized study compared the development of supernumerary human embryos in the presence of 1 mmol/l glutamine and/or 5 mmol/l taurine from the 2-4-cell stage to the blastocyst stage. Blastocyst development and cell numbers were similar in the presence of glutamine or taurine: 52.6% and 58.3% of the embryos reached the blastocyst stage, respectively. Pyruvate uptake was similar in the presence of glutamine or taurine throughout development, as was lactate production after the 8-cell stage. Before this stage, lactate production was 4-fold higher in the presence of taurine (P < 0.001). The proportion of embryos reaching the blastocyst stage was similar with glutamine alone or with glutamine and taurine (62.5% and 47.2% respectively), as were the blastocyst cell numbers (63.0 +/- 4.6 and 61.0 +/- 5.1 respectively). In conclusion, taurine supports development of 2-4-cell human embryos to the blastocyst stage, although it does not further augment the beneficial effects of glutamine. PMID:10469709

  16. Transport of AMPA receptors during long-term potentiation is impaired in rats with hepatic encephalopathy.

    PubMed

    Monfort, Pilar; Piedrafita, Blanca; Felipo, Vicente

    2009-12-01

    Cognitive function is impaired in patients with hepatic encephalopathy. Learning ability is also impaired in rats with hepatic encephalopathy due to portacaval shunts. Long-term potentiation (LTP) in hippocampus, considered the basis of some forms of learning and memory, is impaired in rats with portacaval shunt. We analyzed the mechanisms by which LTP is impaired in these rats. In control rats, application of the tetanus to induce LTP increases phosphorylation of Thr286 of calcium-calmodulin dependent protein kinase II. This activates the kinase which phosphorylates the GluR1 subunit of AMPA receptors in Ser831 and induces its translocation to the post-synaptic densities. All these steps are completely prevented in rats with hepatic encephalopathy in which the tetanus does not induce phosphorylation of CaMKII or GluR1 nor translocation of this subunit to the post-synaptic membrane. This would explain the impairment in LTP in these rats. PMID:19450629

  17. Age-related changes in mRNA levels of hepatic transporters, cytochrome P450 and UDP-glucuronosyltransferase in female rats.

    PubMed

    Kawase, Atsushi; Ito, Ayami; Yamada, Ayano; Iwaki, Masahiro

    2015-06-01

    Hepatic transporters and metabolic enzymes affect drug pharmacokinetics. Limited information exists on the alteration in mRNA levels of hepatic transporters and metabolic enzymes with aging. We examined the effects of aging on the mRNA levels of representative hepatic drug transporters and metabolic enzymes by analyzing their levels in 10-, 30- and 50-week-old male and female rats. Levels of mRNA of drug transporters including multidrug resistance protein (Mdr)1a, multidrug resistance-associated protein (Mrp)2, breast cancer resistance protein (Bcrp) and organic anion-transporting polypeptide (Oatp)1a1, and the metabolic enzymes cytochrome P450 (CYP)3A1, CYP3A2 and UDP-glucuronosyltransferase (UGT)1A1 were analyzed using real-time reverse transcriptase polymerase chain reaction. The mRNA levels of transporters in male rats did not decrease with age, while the mRNA levels of Bcrp and Oatp1a1 in female rats decreased with age. The mRNA levels of CYP3A1 and CYP3A2 in male rats were higher than those in female rats. The mRNA levels of metabolic enzymes decreased with age in female but not male rats. In particular, the mRNA levels of UGT1A1 in 10-week-old female rats were higher than those in male rats. mRNA expression of hepatic transporters and metabolic enzymes are more susceptible to aging in female than male rats. The age-related decreases in the mRNA levels of Bcrp, Oatp1a1, CYP3A1 and CYP3A2 in female rats may affect the metabolism and transport of substrates. This study showed that aging affected the mRNA expression of hepatic transporters and metabolic enzymes in rats. PMID:24899460

  18. Lentiviral hepatitis B pseudotype entry requires sodium taurocholate co-transporting polypeptide and additional hepatocyte-specific factors.

    PubMed

    Meredith, L W; Hu, K; Cheng, X; Howard, C R; Baumert, T F; Balfe, P; van de Graaf, K F; Protzer, U; McKeating, J A

    2016-01-01

    Hepatitis B virus (HBV) is one of the world's major unconquered infections, resulting in progressive liver disease, and current treatments rarely cure infection. A limitation to discovering new therapies is our limited knowledge of HBV entry and dissemination pathways that hinders the development of in vitro culture systems. To address this gap in our understanding we optimized the genesis of infectious lentiviral pseudoparticles (HBVpps). The recent discovery that the bile salt transporter sodium taurocholate co-transporting polypeptide (NTCP) acts as a receptor for HBV enabled us to assess the receptor dependency of HBVpp infection. HBVpps preferentially infect hepatoma cells expressing NTCP, whereas other non-liver cells engineered to express NTCP do not support infection, suggesting that additional hepatocyte-specific factors are required for HBVpp internalization. These results highlight the value of the HBVpp system to dissect the pathways of HBV entry and dissemination. PMID:26474824

  19. Triclosan Disrupts Thyroxine: Contribution of Hepatic Transport to the Mode of Action

    EPA Science Inventory

    Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) (TCS) decreases serum thyroxine (T4) in rats. In previous work, TCS upregulated Phase I and II hepatic metabolism after 4-day exposures in rats. A major data gap in our characterization of the mode of action (MOA) of TCS-induced ...

  20. Meta-analysis of expression of hepatic organic anion-transporting polypeptide (OATP) transporters in cellular systems relative to human liver tissue.

    PubMed

    Badée, Justine; Achour, Brahim; Rostami-Hodjegan, Amin; Galetin, Aleksandra

    2015-04-01

    Organic anion-transporting polypeptide (OATP)1B1, OATP1B3, and OATP2B1 transporters play an important role in hepatic drug disposition. Recently, an increasing number of studies have reported proteomic expression data for OATP transporters. However, systematic analysis and understanding of the actual differences in OATP expression between liver tissue and commonly used cellular systems is lacking. In the current study, meta-analysis was performed to assess the protein expression of OATP transporters reported in hepatocytes relative to liver tissue and to identify any potential correlations in transporter expression levels in the same individual. OATP1B1 was identified as the most abundant uptake transporter at 5.9 ± 8.3, 5.8 ± 3.3, and 4.2 ± 1.7 fmol/μg protein in liver tissue, sandwich-cultured human hepatocytes (SCHH), and cryopreserved suspended hepatocytes, respectively. The rank order in average expression in liver tissue and cellular systems was OATP1B1 > OATP1B3 ≈ OATP2B1. Abundance levels of the OATP transporters investigated were not significantly different between liver and cellular systems, with the exception of OATP2B1 expression in SCHH relative to liver tissue. Analysis of OATP1B1, OATP1B3, and OATP2B1 liver expression data in the same individuals (n = 86) identified weak (OATP1B1-OATP2B1) to moderately (OATP1B3-OATP2B1) significant correlations. A significant weak correlation was noted between OATP1B1 abundance and age of human donors, whereas expression of the OATPs investigated was independent of sex. Implications of the current analysis on the in vitro-in vivo extrapolation of transporter-mediated drug disposition using physiologically based pharmacokinetic models are discussed. PMID:25564656

  1. Taurine in milk and yoghurt marketed in Italy.

    PubMed

    Manzi, Pamela; Pizzoferrato, Laura

    2013-02-01

    Taurine, a free amino acid, was studied as natural compound of different typologies of milk: pasteurized, ultra-high temperature (UHT), microfiltered whole and semi-skimmed cow's milk; pasteurized and UHT goat's whole milk and raw buffalo's whole milk. Moreover, taurine contents in yoghurt from cow and goat's milk were evaluated. The data obtained in this research showed that no significant variations of taurine occurred in cow's milk subjected to different technological processes and between whole and semi-skimmed milk. The amount of taurine was less (p < 0.05) in cow's milk (0.60 mg/100 g) than in goat and buffalo's milk (6.55 and 7.32 mg/100 g, respectively). No significant differences in taurine occurred between goat and buffalo's samples. The amounts of taurine in yoghurt reflected, substantially, the content of this molecule in the milk of the relevant animal species. These results are noteworthy because data available in the literature on this molecule in commercial dairy products are old or few. PMID:22779912

  2. Perinatal taurine exposure affects adult arterial pressure control.

    PubMed

    Roysommuti, Sanya; Wyss, J Michael

    2014-01-01

    Taurine is an abundant, free amino acid found in mammalian cells that contributes to many physiologic functions from that of a simple cell osmolyte to a programmer of adult health and disease. Taurine's contribution extends from conception throughout life, but its most critical exposure period is during perinatal life. In adults, taurine supplementation prevents or alleviates cardiovascular disease and related complications. In contrast, low taurine consumption coincides with increased risk of cardiovascular disease, obesity and type II diabetes. This review focuses on the effects that altered perinatal taurine exposure has on long-term mechanisms that control adult arterial blood pressure and could thereby contribute to arterial hypertension through its ability to program these cardiovascular regulatory mechanisms very early in life. The modifications of these mechanisms can last a lifetime and transfer to the next generation, suggesting that epigenetic mechanisms underlie the changes. The ability of perinatal taurine exposure to influence arterial pressure control mechanisms and hypertension in adult life appears to involve the regulation of growth and development, the central and autonomic nervous system, the renin-angiotensin system, glucose-insulin interaction and changes to heart, blood vessels and kidney function. PMID:23070226

  3. [Taurine is a possible anti-atherosclerotic agent].

    PubMed

    Ito, Takashi; Azuma, Junichi

    2004-05-01

    Atherosclerosis-related ischemic heart diseases are the principal cause of death in the last few years. Recently, several reports implicated that taurine, sulfur-containing beta-amino acid, prevented the progression of atherosclerosis through various anti-pathogenetic modifications. Firstly, taurine treatment inhibited lipid peroxidation and/or lowered serum LDL/VLDL cholesterol and elevated HDL, and as a result, it prevented lipid accumulation on the aortic valve in hypercholesterolaemic animals. Secondly, taurine administration prevented endothelial dysfunction, one of the initial events in the formation of lesions of atherosclerosis, through the amelioration of the impairment of monocyte function. Thirdly, while it is well known that taurine scavenges hypochlorous acid (HOCl) produced by myeloperoxidase in neutrophils and macrophages, recent studies revealed that HOCl was one of the major factors oxidizing LDL, implying that the anti-oxidative role of taurine contributes to the anti-atherosclerotic effect. Additionally, TauCl, produced by the reaction of taurine with HOCl, inhibits the activation of NF-kappaB followed by the inhibition of the production of the pro-inflammatory mediators. PMID:15118255

  4. Neurotrophic effects of taurine on spiral ganglion neurons in vitro.

    PubMed

    Rak, Kristen; Völker, Johannes; Jürgens, Lukas; Scherzad, Agmal; Schendzielorz, Philipp; Radeloff, Andreas; Jablonka, Sibylle; Mlynski, Robert; Hagen, Rudolf

    2014-11-12

    Taurine is an ubiquitary expressed aminosulfonic acid known to play an important role in the development and maintenance of the nervous system. It is distributed in the inner ear, contributing toward the protection of hair cells against aminoglycoside-induced or bilirubin-induced ototoxicity. Thus, the question arises whether taurine also has an influence on the cellular integrity of the auditory neurons. To test this hypothesis, isolated cells of the spiral ganglion were cocultured with taurine or the neurotrophic factors brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) as controls. The analysis included cellular survival rate and neurite outgrowth. With application of taurine, the survival of glial cells and neurons was stimulated in a similar pattern, whereas BDNF and NT-3 only effected neuronal survival. Furthermore, administration of taurine resulted in enhanced neurite outgrowth comparable with the effect of the neurotrophic factors. These new insights on the neuromodulatory effects of taurine on auditory neurons suggest the use of this aminosulfonic acid to reduce the degeneration of auditory neurons in sensorineural hearing loss. Consecutively, a new therapeutical approach for the therapy of hearing impairment could be discussed. PMID:25202928

  5. Effects of taurine on gut microbiota and metabolism in mice.

    PubMed

    Yu, Haining; Guo, Zhengzhao; Shen, Shengrong; Shan, Weiguang

    2016-07-01

    As being a necessary amino acid, taurine plays an important role in the regulation of neuroendocrine functions and nutrition. In this study, effects of taurine on mice gut microbes and metabolism were investigated. BALB/C mice were randomly divided into three experimental groups: The first group was administered saline (CK), the second was administered 165 mg/kg natural taurine (NE) and the third one administered 165 mg/kg synthetic taurine (CS). Gut microbiota composition in mice feces was analyzed by metagenomics technology, and the content of short-chain fatty acids (SCFA) in mice feces was detected by gas chromatography (GC), while the concentrations of lipopolysaccharide (LPS) and superoxide dismutase (SOD) were detected by a LPS ELISA kit and a SOD assay kit, respectively. The results showed that the effect of taurine on gut microbiota could reduce the abundance of Proteobacteria, especially Helicobacter. Moreover, we found that the SCFA content was increased in feces of the NE group while LPS content was decreased in serum of the NE group; the SOD activity in serum and livers of the NE and CS groups were not changed significantly compare to that of the CK group. In conclusion, taurine could regulate the gut micro-ecology, which might be of benefit to health by inhibiting the growth of harmful bacteria, accelerating the production of SCFA and reducing LPS concentration. PMID:27026373

  6. Two Distinct Modes of Hypoosmotic Medium-Induced Release of Excitatory Amino Acids and Taurine in the Rat Brain In Vivo

    PubMed Central

    Haskew-Layton, Renée E.; Rudkouskaya, Alena; Jin, Yiqiang; Feustel, Paul J.; Kimelberg, Harold K.; Mongin, Alexander A.

    2008-01-01

    A variety of physiological and pathological factors induce cellular swelling in the brain. Changes in cell volume activate several types of ion channels, which mediate the release of inorganic and organic osmolytes and allow for compensatory cell volume decrease. Volume-regulated anion channels (VRAC) are thought to be responsible for the release of some of organic osmolytes, including the excitatory neurotransmitters glutamate and aspartate. In the present study, we compared the in vivo properties of the swelling-activated release of glutamate, aspartate, and another major brain osmolyte taurine. Cell swelling was induced by perfusion of hypoosmotic (low [NaCl]) medium via a microdialysis probe placed in the rat cortex. The hypoosmotic medium produced several-fold increases in the extracellular levels of glutamate, aspartate and taurine. However, the release of the excitatory amino acids differed from the release of taurine in several respects including: (i) kinetic properties, (ii) sensitivity to isoosmotic changes in [NaCl], and (iii) sensitivity to hydrogen peroxide, which is known to modulate VRAC. Consistent with the involvement of VRAC, hypoosmotic medium-induced release of the excitatory amino acids was inhibited by the anion channel blocker DNDS, but not by the glutamate transporter inhibitor TBOA or Cd2+, which inhibits exocytosis. In order to elucidate the mechanisms contributing to taurine release, we studied its release properties in cultured astrocytes and cortical synaptosomes. Similarities between the results obtained in vivo and in synaptosomes suggest that the swelling-activated release of taurine in vivo may be of neuronal origin. Taken together, our findings indicate that different transport mechanisms and/or distinct cellular sources mediate hypoosmotic medium-induced release of the excitatory amino acids and taurine in vivo. PMID:18958155

  7. Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor.

    PubMed

    Yamada, Akihiro; Maeda, Kazuya; Kamiyama, Emi; Sugiyama, Daisuke; Kondo, Tsunenori; Shiroyanagi, Yoshiyuki; Nakazawa, Hayakazu; Okano, Teruo; Adachi, Masashi; Schuetz, John D; Adachi, Yasuhisa; Hu, Zhuohan; Kusuhara, Hiroyuki; Sugiyama, Yuichi

    2007-12-01

    Olmesartan, a novel angiotensin II AT1-receptor antagonist, is excreted into both bile and urine, with minimal metabolism. Because olmesartan is a hydrophilic anionic compound, some transporters could be involved in its hepatic and renal clearance. In this study, we characterized the role of human drug transporters in the pharmacokinetics of olmesartan and determined the contribution of each transporter to the overall clearance of olmesartan. Olmesartan was significantly taken up into human embryonic kidney 293 cells expressing organic anion-transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, and OAT3. We also observed its saturable uptake into human hepatocytes and kidney slices. Estimated from the relative activity factor method and application of specific inhibitors, the relative contributions of OATP1B1 and OATP1B3 to the uptake of olmesartan in human hepatocytes were almost the same, whereas OAT3 was predominantly involved in its uptake in kidney slices. The vectorial transport of olmesartan was observed in OATP1B1/multidrug resistance-associated protein (MRP) 2 double transfectants, but not in OATP1B1/multidrug resistance (MDR) 1 and OATP1B1/breast cancer resistance protein (BCRP) transfectants. ATP-dependent transport into membrane vesicles expressing human MRP2 and MRP4 was clearly observed, with K(m) values of 14.9 and 26.2 microM, respectively, whereas the urinary excretion of olmesartan in Mrp4-knockout mice was not different from that of control mice. We also investigated the transcellular transport of olmesartan medoxomil, a prodrug of olmesartan. Vectorial basal-to-apical transport was observed in OATP1B1/MRP2, OATP1B1/MDR1 double, and OATP1B1/BCRP double transfectants, suggesting the possible involvement of MRP2, MDR1, and BCRP in the limit of intestinal absorption of olmesartan medoxomil. From these results, we suggest that multiple transporters make a significant contribution to the pharmacokinetics of olmesartan and

  8. Lycopene protects against atrazine-induced hepatic ionic homeostasis disturbance by modulating ion-transporting ATPases.

    PubMed

    Lin, Jia; Zhao, Hua-Shan; Xiang, Li-Run; Xia, Jun; Wang, Li-Li; Li, Xue-Nan; Li, Jin-Long; Zhang, Ying

    2016-01-01

    The aim of this study was to evaluate the possible chemoprotective role of lycopene (LYC) against atrazine (ATR)-induced ionic disorder and hepatotoxicity in mice. Male kunming mice were treated with LYC (5mg/kg) and/or ATR (50mg/kg or 200mg/kg) by lavage administration for 21days. Ionic disorder was assessed by determining the Na(+), K(+) and Ca(2+) content and the alteration in ATP enzymes (ATPases) including Na(+)-K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase and Ca(2+)-Mg(2+)-ATPase and the mRNA levels of ATPase's subunits in liver. ATR caused the increases of alanine aminotransferase and aspartate aminotransferase activities and histological changes. LYC pretreatment significantly protected liver against ATR-caused alternation. The significant effect of ATR and LYC on the K(+) and Mg(2+) content in liver was not observed, but ATR increased hepatic Na(+)-K(+)-ATPase activity and decreased Mg(2+)-ATPase and Ca(2+)-Mg(2+)-ATPase activity. The mRNA expressions of Na(+)-K(+)-ATPase subunits were regulated significantly by ATR. A significant increase of Ca(2+) content and seven down-regulated mRNA expressions of Ca(2+)-ATPase subunits and a decrease of Ca(2+)-ATPase activity were observed in the ATR-treated mice. Notably, LYC modulated these ATR-induced alterations of ATPase activity and mRNA expression of their subunits. These results suggest that ATR presents hepatotoxicity via regulating hepatic ATPase's activities and their subunit transcriptions and inducing ionic disorder. LYC protects liver against ATR-induced hepatotoxicity, significantly. LYC modulated hepatic ionic homeostasis disturbance via regulation of ATPase activities and their subunits' (1a1, 1b3, 1b4 and 2b4) transcriptions. In summary, these effects play a critical role of LYC-mediated chemoprevention against ATR-induced hepatotoxicity. PMID:26476475

  9. Anti-Inflammatory Effect of Taurine in Burned Patients

    PubMed Central

    Lak, Sima; Ostadrahimi, Alireza; Nagili, Behrooz; Asghari-Jafarabadi, Mohammad; Beigzali, Sanaz; Salehi, Feridoon; Djafarzadeh, Roxana

    2015-01-01

    Purpose: Burn induced inflammatory response can be mediated by reactive oxygen metabolites and accompanied by multiple organ dysfunction. Taurine has protective effects against various inflammatory conditions. The aim of this study was to determine the effect of Taurine supplement in thermal burn victims. Methods: Thirty patients with severe thermal burns were enrolled in this randomized double-blinded clinical trial. These patients were randomly divided into two equal groups (namely Control and Taurine groups), where both received isocaloric and isonitrogenous formula. One group was supplemented with 50 mg/kg of Taurine per day for a duration of 10 days. Blood samples were obtained to measure Interleukin-10 (IL-10), high-sensitivity C-reactive protein (hs-CRP), and Tumor Necrosis Factor alpha (TNF-α) levels at the beginning and the end of the study. Results: Change in serum level of IL-10 in Taurine group was more than Control group [-13.60(-31.40, -10.40) compared to -4.00(-20.00, -0.20) respectively; P = 0.030]. This change was significant in patients with more than 30% TBSA of burn [-14.20(-31.40, -10.40) compared to -2.40(-9.60, 0.40) respectively; P = 0.013]. As for the hs-CRP and TNF-α levels, the difference between the two groups were not significant. Conclusion: Based on the results obtained, Taurine supplement showed a positive outcome on anti-inflammatory cytokine IL-10 in all burn patients. This effect was even more significant in patients with higher percentage of burn area. Taurine had no significant effect on the inflammatory marker hs-CRP and the pro-inflammatory cytokine TNF-α level. For a more thorough verification, measurement of a wider range of inflammatory cytokines in more frequent time intervals are suggested. PMID:26819926

  10. Effect of allyl alcohol on hepatic transporter expression: Zonal patterns of expression and role of Kupffer cell function

    PubMed Central

    Campion, Sarah N.; Tatis-Rios, Cristina; Augustine, Lisa M.; Goedken, Michael J.; van Rooijen, Nico; Cherrington, Nathan J.; Manautou, José E.

    2015-01-01

    During APAP toxicity, activation of Kupffer cells is critical for protection from hepatotoxicity and up-regulation of multidrug resistance-associated protein 4 (Mrp4) in centrilobular hepatocytes. The present study was performed to determine the expression profile of uptake and efflux transporters in mouse liver following treatment with allyl alcohol (AlOH), a periportal hepatotoxicant. This study also investigated the role of Kupffer cells in AlOH hepatotoxicity, and whether changes in transport protein expression by AlOH are dependent on the presence of Kupffer cells. C57BL/6J mice received 0.1 ml clodronate liposomes to deplete Kupffer cells or empty liposomes 48 h prior to dosing with 60 mg/kg AlOH, i.p. Hepatotoxicity was assessed by plasma ALT and histopathology. Hepatic transporter mRNA and protein expression were determined by branched DNA signal amplification assay and Western blotting, respectively. Depletion of Kupffer cells by liposomal clodronate treatment resulted in heightened susceptibility to AlOH toxicity. Exposure to AlOH increased mRNA levels of several Mrp genes, while decreasing organic anion transporting polypeptides (Oatps) mRNA expression. Protein analysis mirrored many of these mRNA changes. The presence of Kupffer cells was not required for the observed changes in uptake and efflux transporters induced by AlOH. Immunofluorescent analysis revealed enhanced Mrp4 staining exclusively in centrilobular hepatocytes of AlOH treated mice. These findings demonstrate that Kupffer cells are protective from AlOH toxicity and that induction of Mrp4 occurs in liver regions away from areas of AlOH damage independent of Kupffer cell function. These results suggest that Kupffer cell mediators do not play a role in mediating centrilobular Mrp4 induction in response to periportal damage by AlOH. PMID:19371622

  11. Roles of changes in active glutamine transport in brain edema development during hepatic encephalopathy: an emerging concept.

    PubMed

    Zielińska, Magdalena; Popek, Mariusz; Albrecht, Jan

    2014-01-01

    Excessive glutamine (Gln) synthesis in ammonia-overloaded astrocytes contributes to astrocytic swelling and brain edema, the major complication of hepatic encephalopathy (HE). Much of the newly formed Gln is believed to enter mitochondria, where it is recycled to ammonia, which causes mitochondrial dysfunction (a "Trojan horse" mode of action). A portion of Gln may increase osmotic pressure in astrocytes and the interstitial space, directly and independently contributing to brain tissue swelling. Here we discuss the possibility that altered functioning of Gln transport proteins located in the cellular or mitochondrial membranes, modulates the effects of increased Gln synthesis. Accumulation of excess Gln in mitochondria involves a carrier-mediated transport which is activated by ammonia. Studies on the expression of the cell membrane N-system transporters SN1 (SNAT3) and SN2 (SNAT5), which mediate Gln efflux from astrocytes rendered HE model-dependent effects. HE lowered the expression of SN1 at the RNA and protein level in the cerebral cortex (cc) in the thioacetamide (TAA) model of HE and the effect paralleled induction of cerebral cortical edema. Neither SN1 nor SN2 expression was affected by simple hyperammonemia, which produces no cc edema. TAA-induced HE is also associated with decreased expression of mRNA coding for the system A carriers SAT1 and SAT2, which stimulate Gln influx to neurons. Taken together, changes in the expression of Gln transporters during HE appear to favor retention of Gln in astrocytes and/or the interstitial space of the brain. HE may also affect arginine (Arg)/Gln exchange across the astrocytic cell membrane due to changes in the expression of the hybrid Arg/Gln transporter y(+)LAT2. Gln export from brain across the blood-brain barrier may be stimulated by HE via its increased exchange with peripheral tryptophan. PMID:24072671

  12. Effect of allyl alcohol on hepatic transporter expression: Zonal patterns of expression and role of Kupffer cell function

    SciTech Connect

    Campion, Sarah N.; Tatis-Rios, Cristina; Augustine, Lisa M.; Goedken, Michael J.; Rooijen, Nico van; Cherrington, Nathan J.; Manautou, Jose E.

    2009-04-01

    During APAP toxicity, activation of Kupffer cells is critical for protection from hepatotoxicity and up-regulation of multidrug resistance-associated protein 4 (Mrp4) in centrilobular hepatocytes. The present study was performed to determine the expression profile of uptake and efflux transporters in mouse liver following treatment with allyl alcohol (AlOH), a periportal hepatotoxicant. This study also investigated the role of Kupffer cells in AlOH hepatotoxicity, and whether changes in transport protein expression by AlOH are dependent on the presence of Kupffer cells. C57BL/6J mice received 0.1 ml clodronate liposomes to deplete Kupffer cells or empty liposomes 48 h prior to dosing with 60 mg/kg AlOH, i.p. Hepatotoxicity was assessed by plasma ALT and histopathology. Hepatic transporter mRNA and protein expression were determined by branched DNA signal amplification assay and Western blotting, respectively. Depletion of Kupffer cells by liposomal clodronate treatment resulted in heightened susceptibility to AlOH toxicity. Exposure to AlOH increased mRNA levels of several Mrp genes, while decreasing organic anion transporting polypeptides (Oatps) mRNA expression. Protein analysis mirrored many of these mRNA changes. The presence of Kupffer cells was not required for the observed changes in uptake and efflux transporters induced by AlOH. Immunofluorescent analysis revealed enhanced Mrp4 staining exclusively in centrilobular hepatocytes of AlOH treated mice. These findings demonstrate that Kupffer cells are protective from AlOH toxicity and that induction of Mrp4 occurs in liver regions away from areas of AlOH damage independent of Kupffer cell function. These results suggest that Kupffer cell mediators do not play a role in mediating centrilobular Mrp4 induction in response to periportal damage by AlOH.

  13. Characterization of Transporters in the Hepatic Uptake of TAK-475 M-I, a Squalene Synthase Inhibitor, in Rats and Humans.

    PubMed

    Ebihara, T; Takeuchi, T; Moriya, Y; Tagawa, Y; Kondo, T; Moriwaki, T; Asahi, S

    2016-06-01

    TAK-475 (lapaquistat acetate) is a squalene synthase inhibitor and M-I is a pharmacologically active metabolite of TAK-475. Preclinical pharmacokinetic studies have demonstrated that most of the dosed TAK-475 was hydrolyzed to M-I during the absorption process and the concentrations of M-I in the liver, the main organ of cholesterol biosynthesis, were much higher than those in the plasma after oral administration to rats. In the present study, the mechanism of the hepatic uptake of M-I was investigated.The uptake studies of (14)C-labeled M-I into rat and human hepatocytes indicated that the uptakes of M-I were concentrative, temperature-dependent and saturable in both species with Km values of 4.7 and 2.8 μmol/L, respectively. M-I uptake was also inhibited by cyclosporin A, an inhibitor for hepatic uptake transporters including organic anion transporting polypeptide (OATP). In the human hepatocytes, M-I uptake was hardly inhibited by estrone 3-sulfate as an inhibitor for OATP1B1, and most of the M-I uptake was Na(+)-independent. Uptake studies using human transporter-expressing cells revealed the saturable uptake of M-I for OATP1B3 with a Km of 2.13 μmol/L. No obvious uptake of M-I was observed in the OATP1B1-expressing cells.These results indicated that M-I was taken up into hepatocytes via transporters in both rats and humans. OATP1B3 would be mainly involved in the hepatic uptake of M-I in humans. These findings suggested that hepatic uptake transporters might contribute to the liver-selective inhibition of cholesterol synthesis by TAK-475. This is the first to clarify a carrier-mediated hepatic uptake mechanism for squalene synthase inhibitors. PMID:27011383

  14. Inhibition of Human Hepatic Bile Acid Transporters by Tolvaptan and Metabolites: Contributing Factors to Drug-Induced Liver Injury?

    PubMed

    Slizgi, Jason R; Lu, Yang; Brouwer, Kenneth R; St Claire, Robert L; Freeman, Kimberly M; Pan, Maxwell; Brock, William J; Brouwer, Kim L R

    2016-01-01

    Tolvaptan is a vasopressin V(2)-receptor antagonist that has shown promise in treating Autosomal Dominant Polycystic Kidney Disease (ADPKD). Tolvaptan was, however, associated with liver injury in some ADPKD patients. Inhibition of bile acid transporters may be contributing factors to drug-induced liver injury. In this study, the ability of tolvaptan and two metabolites, DM-4103 and DM-4107, to inhibit human hepatic transporters (NTCP, BSEP, MRP2, MRP3, and MRP4) and bile acid transport in sandwich-cultured human hepatocytes (SCHH) was explored. IC(50) values were determined for tolvaptan, DM-4103 and DM-4107 inhibition of NTCP (∼41.5, 16.3, and 95.6 μM, respectively), BSEP (31.6, 4.15, and 119 μM, respectively), MRP2 (>50, ∼51.0, and >200 μM, respectively), MRP3 (>50, ∼44.6, and 61.2 μM, respectively), and MRP4 (>50, 4.26, and 37.9 μM, respectively). At the therapeutic dose of tolvaptan (90 mg), DM-4103 exhibited a C(max)/IC(50) value >0.1 for NTCP, BSEP, MRP2, MRP3, and MRP4. Tolvaptan accumulation in SCHH was extensive and not sodium-dependent; intracellular concentrations were ∼500 μM after a 10-min incubation duration with tolvaptan (15 μM). The biliary clearance of taurocholic acid (TCA) decreased by 43% when SCHH were co-incubated with tolvaptan (15 μM) and TCA (2.5 μM). When tolvaptan (15 μM) was co-incubated with 2.5 μM of chenodeoxycholic acid, taurochenodeoxycholic acid, or glycochenodeoxycholic acid in separate studies, the cellular accumulation of these bile acids increased by 1.30-, 1.68-, and 2.16-fold, respectively. Based on these data, inhibition of hepatic bile acid transport may be one of the biological mechanisms underlying tolvaptan-associated liver injury in patients with ADPKD. PMID:26507107

  15. mTOR ensures increased release and reduced uptake of the organic osmolyte taurine under hypoosmotic conditions in mouse fibroblasts.

    PubMed

    Lambert, Ian Henry; Jensen, Jane Vendelbo; Pedersen, Per Amstrup

    2014-06-01

    Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that modulates translation in response to growth factors and alterations in nutrient availability following hypoxia and DNA damage. Here we demonstrate that mTOR activity in Ehrlich Lettré ascites (ELA) cells is transiently increased within minutes following osmotic cell swelling and that inhibition of phosphatidylinositol-3-phosphatase (PTEN) counteracts the upstream phosphatidylinositol kinase and potentiates mTOR activity. PTEN inhibition concomitantly potentiates swelling-induced taurine release via the volume-sensitive transporter for organic osmolytes and anion channels (VSOAC) and enhances swelling-induced inhibition of taurine uptake via the taurine-specific transporter (TauT). Chronic osmotic stress, i.e., exposure to hypotonic or hypertonic media for 24 h, reduces and increases mTOR activity in ELA cells, respectively. Using rapamycin, we demonstrate that mTOR inhibition is accompanied by reduction in TauT activity and increase in VSOAC activity in cells expressing high (NIH3T3 fibroblasts) or low (ELA) amounts of mTOR protein. The effect of mTOR inhibition on TauT activity reflects reduced TauT mRNA, TauT protein abundance, and an overall reduction in protein synthesis, whereas the effect on VSOAC is mimicked by catalase inhibition and correlates with reduced catalase mRNA abundance. Hence, mTOR activity favors loss of taurine following hypoosmotic cell swelling, i.e., release via VSOAC and uptake via TauT during acute hypotonic exposure is potentiated and reduced, respectively, by phosphorylation involving mTOR and/or the kinases upstream to mTOR. Decrease in TauT activity during chronic hypotonic exposure, on the other hand, involves reduction in expression/activity of TauT and enzymes in antioxidative defense. PMID:24696147

  16. Alterations in hepatic mRNA expression of phase II enzymes and xenobiotic transporters after targeted disruption of hepatocyte nuclear factor 4 alpha.

    PubMed

    Lu, Hong; Gonzalez, Frank J; Klaassen, Curtis

    2010-12-01

    Hepatocyte nuclear factor 4 alpha (HNF4a) is a liver-enriched master regulator of liver function. HNF4a is important in regulating hepatic expression of certain cytochrome P450s. The purpose of this study was to use mice lacking HNF4a expression in liver (HNF4a-HNull) to elucidate the role of HNF4a in regulating hepatic expression of phase II enzymes and transporters in mice. Compared with male wild-type mice, HNF4a-HNull male mouse livers had (1) markedly lower messenger RNAs (mRNAs) encoding the uptake transporters sodium taurocholate cotransporting polypeptide, organic anion transporting polypeptide (Oatp) 1a1, Oatp2b1, organic anion transporter 2, sodium phosphate cotransporter type 1, sulfate anion transporter 1, sodium-dependent vitamin C transporter 1, the phase II enzymes Uridine 5'-diphospho (UDP)-glucuronosyltransferase (Ugt) 2a3, Ugt2b1, Ugt3a1, Ugt3a2, sulfotransferase (Sult) 1a1, Sult1b1, Sult5a1, the efflux transporters multidrug resistance-associated protein (Mrp) 6, and multidrug and toxin extrusion 1; (2) moderately lower mRNAs encoding Oatp1b2, organic cation transporter (Oct) 1, Ugt1a5, Ugt1a9, glutathione S-transferase (Gst) m4, Gstm6, and breast cancer resistance protein; but (3) higher mRNAs encoding Oatp1a4, Octn2, Ugt1a1, Sult1e1, Sult2a2, Gsta4, Gstm1-m3, multidrug resistance protein (Mdr) 1a, Mrp3, and Mrp4. Hepatic signaling of nuclear factor E2-related factor 2 and pregnane X receptor appear to be activated in HNF4a-HNull mice. In conclusion, HNF4a deficiency markedly alters hepatic mRNA expression of a large number of phase II enzymes and transporters, probably because of the loss of HNF4a, which is a transactivator and a determinant of gender-specific expression and/or adaptive activation of signaling pathways important in hepatic regulation of these phase II enzymes and transporters. PMID:20935164

  17. Sulphoacetaldehyde acetyltransferase yields acetyl phosphate: purification from Alcaligenes defragrans and gene clusters in taurine degradation.

    PubMed

    Ruff, Jürgen; Denger, Karin; Cook, Alasdair M

    2003-01-15

    The facultatively anaerobic bacterium Alcaligenes defragrans NKNTAU was found to oxidize taurine (2-aminoethanesulphonate) with nitrate as the terminal electron acceptor. Taurine was transaminated to 2-sulphoacetaldehyde. This was not converted into sulphite and acetate by a "sulphoacetaldehyde sulpho-lyase" (EC 4.4.1.12), but into sulphite and acetyl phosphate, which was identified by three methods. The enzyme, which required the addition of phosphate, thiamin diphosphate and Mg(2+) ions for activity, was renamed sulphoacetaldehyde acetyltransferase (Xsc; EC 2.3.1.-). Inducible Xsc was expressed at high levels, and a three-step 11-fold purification yielded an essentially homogeneous soluble protein, which was a homotetramer in its native form; the molecular mass of the subunit was found to be between about 63 kDa (SDS/PAGE) and 65.3 kDa (matrix-assisted laser-desorption ionization-time-of-flight MS). The N-terminal and two internal amino acid sequences were determined, and PCR primers were generated. The xsc gene was amplified and sequenced; the derived molecular mass of the processed protein was 65.0 kDa. The downstream gene presumably encoded the inducible phosphate acetyltransferase (Pta) found in crude extracts. The desulphonative enzymes ("EC 4.4.1.12") from Achromobacter xylosoxidans NCIMB 10751 and Desulfonispora thiosulfatigenes GKNTAU were shown to be Xscs. We detected at least three subclasses of xsc in Proteobacteria and in Gram-positive bacteria, and they comprised a distinct group within the acetohydroxyacid synthase supergene family. Genome sequencing data revealed xsc genes in Burkholderia fungorum (80% sequence identity) and Sinorhizobium meliloti (61%) with closely linked pta genes. Different patterns of regulation for the transport and dissimilation of taurine were hypothesized for S. meliloti and B. fungorum. PMID:12358600

  18. Sulphoacetaldehyde acetyltransferase yields acetyl phosphate: purification from Alcaligenes defragrans and gene clusters in taurine degradation.

    PubMed Central

    Ruff, Jürgen; Denger, Karin; Cook, Alasdair M

    2003-01-01

    The facultatively anaerobic bacterium Alcaligenes defragrans NKNTAU was found to oxidize taurine (2-aminoethanesulphonate) with nitrate as the terminal electron acceptor. Taurine was transaminated to 2-sulphoacetaldehyde. This was not converted into sulphite and acetate by a "sulphoacetaldehyde sulpho-lyase" (EC 4.4.1.12), but into sulphite and acetyl phosphate, which was identified by three methods. The enzyme, which required the addition of phosphate, thiamin diphosphate and Mg(2+) ions for activity, was renamed sulphoacetaldehyde acetyltransferase (Xsc; EC 2.3.1.-). Inducible Xsc was expressed at high levels, and a three-step 11-fold purification yielded an essentially homogeneous soluble protein, which was a homotetramer in its native form; the molecular mass of the subunit was found to be between about 63 kDa (SDS/PAGE) and 65.3 kDa (matrix-assisted laser-desorption ionization-time-of-flight MS). The N-terminal and two internal amino acid sequences were determined, and PCR primers were generated. The xsc gene was amplified and sequenced; the derived molecular mass of the processed protein was 65.0 kDa. The downstream gene presumably encoded the inducible phosphate acetyltransferase (Pta) found in crude extracts. The desulphonative enzymes ("EC 4.4.1.12") from Achromobacter xylosoxidans NCIMB 10751 and Desulfonispora thiosulfatigenes GKNTAU were shown to be Xscs. We detected at least three subclasses of xsc in Proteobacteria and in Gram-positive bacteria, and they comprised a distinct group within the acetohydroxyacid synthase supergene family. Genome sequencing data revealed xsc genes in Burkholderia fungorum (80% sequence identity) and Sinorhizobium meliloti (61%) with closely linked pta genes. Different patterns of regulation for the transport and dissimilation of taurine were hypothesized for S. meliloti and B. fungorum. PMID:12358600

  19. Mechanism of Polybrominated Diphenyl Ether Uptake into the Liver: PBDE Congeners Are Substrates of Human Hepatic OATP Transporters

    PubMed Central

    Pacyniak, Erik; Roth, Megan; Hagenbuch, Bruno; Guo, Grace L.

    2010-01-01

    Polybrominated diphenyl ethers (PBDEs) are flame-retardants that upon chronic exposure enter the liver where they are biotransformed to potentially toxic metabolites. The mechanism by which PBDEs enter the liver is not known. However, due to their large molecular weights (MWs ∼485 to 1000 Da), they cannot enter hepatocytes by simple diffusion. Organic anion–transporting polypeptides (OATPs) are responsible for hepatic uptake of a variety of amphipathic compounds of MWs larger than 350 Da. Therefore, in the present study, Chinese hamster ovary cell lines expressing OATP1B1, OATP1B3, and OATP2B1 were used to test the hypothesis that OATPs expressed in human hepatocytes would be responsible for the uptake of PBDE congeners 47, 99, and 153. The results demonstrated that PBDE congeners inhibited OATP1B1- and OATP1B3-mediated uptake of estradiol-17-β-glucuronide as well as OATP2B1-mediated uptake of estrone-3-sulfate in a concentration-dependent manner. Direct uptake studies confirmed that all three PBDE congeners are substrates for the three tested hepatic OATPs. Detailed kinetic analysis revealed that OATP1B1 transported 2,2′,4,4′-tetrabromodiphenyl ether (BDE47) with the highest affinity (Km = 0.31μM) followed by 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99) (Km = 0.91μM) and 2,2′,4,4′,5,5′-hexabromodiphenyl ether (BDE153) (Km = 1.91μM). For OATP1B3, the order was the same (BDE47: Km = 0.41μM; BDE99: Km = 0.70μM; BDE153: Km = 1.66μM), while OATP2B1 transported all three congeners with similar affinities (BDE47: Km = 0.81μM; BDE99: Km = 0.87μM; BDE153: Km = 0.65μM). These results clearly suggest that uptake of PBDEs via these OATPs is a mechanism responsible for liver-specific accumulation of PBDEs. PMID:20176623

  20. Persistent Hepatitis C Virus Infection Impairs Ribavirin Antiviral Activity through Clathrin-Mediated Trafficking of Equilibrative Nucleoside Transporter 1

    PubMed Central

    Panigrahi, Rajesh; Chandra, Partha K.; Ferraris, Pauline; Kurt, Ramazan; Song, Kyoungsub; Garry, Robert F.; Reiss, Krzysztof; Coe, Imogen R.; Furihata, Tomomi; Balart, Luis A.; Wu, Tong

    2014-01-01

    ABSTRACT Ribavirin (RBV) continues to be an important component of interferon-free hepatitis C treatment regimens, as RBV alone does not inhibit hepatitis C virus (HCV) replication effectively; the reason for this ineffectiveness has not been established. In this study, we investigated the RBV resistance mechanism using a persistently HCV-infected cell culture system. The antiviral activity of RBV against HCV was progressively impaired in the persistently infected culture, whereas interferon lambda 1 (IFN-λ1), a type III IFN, showed a strong antiviral response and induced viral clearance. We found that HCV replication in persistently infected cultures induces an autophagy response that impairs RBV uptake by preventing the expression of equilibrative nucleoside transporter 1 (ENT1). The Huh-7.5 cell line treated with an autophagy inducer, Torin 1, downregulated membrane expression of ENT1 and terminated RBV uptake. In contrast, the autophagy inhibitors hydroxychloroquine (HCQ), 3-methyladenine (3-MA), and bafilomycin A1 (BafA1) prevented ENT1 degradation and enhanced RBV antiviral activity. The HCV-induced autophagy response, as well as treatment with Torin 1, degrades clathrin heavy chain expression in a hepatoma cell line. Reduced expression of the clathrin heavy chain by HCV prevents ENT1 recycling to the plasma membrane and forces ENT1 to the lysosome for degradation. This study provides a potential mechanism for the impairment of RBV antiviral activity in persistently HCV-infected cell cultures and suggests that inhibition of the HCV-induced autophagy response could be used as a strategy for improving RBV antiviral activity against HCV infection. IMPORTANCE The results from this work will allow a review of the competing theories of antiviral therapy development in the field of HCV virology. Ribavirin (RBV) remains an important component of interferon-free hepatitis C treatment regimens. The reason why RBV alone does not inhibit HCV replication effectively has

  1. The beneficial effects of taurine in preventing metabolic syndrome.

    PubMed

    Chen, Wen; Guo, Junxia; Zhang, Yanzhen; Zhang, Jing

    2016-04-20

    Metabolic syndrome, a cluster of risk factors for diabetes and cardiovascular disease, has become a very serious public health concern. A number of studies have provided evidence that taurine has an efficient action against metabolic syndrome, which includes reducing triglycerides to prevent obesity, improving insulin resistance to regulate glucose metabolism, lowering cholesterol (especially decreasing VLDL + LDL cholesterol and increasing HDL cholesterol) to prevent diet-induced hypercholesterolemia, and regulating the renin-angiotensin-aldosterone system and the kallikrein-kinin system etc. to reduce blood pressure. This review summarizes the data from in vitro, animal and limited human studies of beneficial effects of taurine on obesity, dyslipidaemia, diabetes mellitus and hypertension, and addresses the possible metabolic and molecular mechanisms of the prevention of metabolic syndrome by taurine. PMID:26918249

  2. Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model

    PubMed Central

    Lee, Eun Soo; Hyun, Miri; Kim, Hong Min; Choi, Yoon Jung; Lee, Eun Young; Yadav, Dhananjay; Chung, Choon Hee

    2014-01-01

    The overexpression of vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n = 10), OLETF rats as diabetic control group (n = 10), and OLETF rats treated with taurine group (n = 10). We treated taurine (200 mg/kg/day) for 20 weeks and treated high glucose (HG, 30 mM) with or without taurine (30 mM) in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS) levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model. PMID:24707287

  3. Two Different Conformations in Hepatitis C Virus p7 Protein Account for Proton Transport and Dye Release

    PubMed Central

    Vararattanavech, Ardcharaporn; Torres, Jaume

    2014-01-01

    The p7 protein from the hepatitis C virus (HCV) is a 63 amino acid long polypeptide that is essential for replication, and is involved in protein trafficking and proton transport. Therefore, p7 is a possible target for antivirals. The consensus model for the channel formed by p7 protein is a hexameric or heptameric oligomer of α-helical hairpin monomers, each having two transmembrane domains, TM1 and TM2, where the N-terminal TM1 would face the lumen of this channel. A reported high-throughput functional assay to search for p7 channel inhibitors is based on carboxyfluorescein (CF) release from liposomes after p7 addition. However, the rationale for the dual ability of p7 to serve as an ion or proton channel in the infected cell, and to permeabilize membranes to large molecules like CF is not clear. We have recreated both activities in vitro, examining the conformation present in these assays using infrared spectroscopy. Our results indicate that an α-helical form of p7, which can transport protons, is not able to elicit CF release. In contrast, membrane permeabilization to CF is observed when p7 contains a high percentage of β-structure, or when using a C-terminal fragment of p7, encompassing TM2. We propose that the reported inhibitory effect of some small compounds, e.g., rimantadine, on both CF release and proton transport can be explained via binding to the membrane-inserted C-terminal half of p7, increasing its rigidity, in a similar way to the influenza A M2-rimantadine interaction. PMID:24409277

  4. Localization of Xenobiotic Transporter OCTN1/SLC22A4 in Hepatic Stellate Cells and Its Protective Role in Liver Fibrosis.

    PubMed

    Tang, Yaliang; Masuo, Yusuke; Sakai, Yoshio; Wakayama, Tomohiko; Sugiura, Tomoko; Harada, Ryuichi; Futatsugi, Azusa; Komura, Takuya; Nakamichi, Noritaka; Sekiguchi, Hirotaka; Sutoh, Keita; Usumi, Koji; Iseki, Shoichi; Kaneko, Shuichi; Kato, Yukio

    2016-05-01

    Xenobiotic transporters play key roles in disposition of certain therapeutic agents, although limited information is available on their roles other than pharmacokinetic issues. Here, suppressive effect of multispecific organic cation transporter OCTN1/SLC22A4 on liver fibrosis was proposed in liver injury models. After injection of hepatotoxins such as dimethylnitrosamine (DMN) or concanavalin A, hepatic fibrosis, and oxidative stress, evaluated in terms of Sirius red and 4-hydroxy-2-nonenal staining, respectively, were more severe in liver of octn1/slc22a4 gene knockout (octn1(-/-)) mice than that in wild-type mice. DMN treatment markedly increased α-smooth muscle actin and F4/80, markers of activated stellate and Kupffer cells, respectively, in liver of octn1(-/-), but had less effect in wild-type mice. Thus, octn1/slc22a4 gene deletion results in more severe hepatic fibrosis, oxidative stress, and inflammation. DMN-treated wild-type mice showed increased Octn1 staining and hepatic concentration of its food-derived antioxidant ergothioneine (ERGO). The upregulated Octn1 was co-localized with α-smooth muscle actin. Functional expression of Octn1 was demonstrated in activated human hepatic stellate cell lines, LI90 and LX-2. Provision of ERGO-rich feed ameliorated DMN-induced liver fibrosis and oxidative stress. Overall, Octn1 is upregulated in activated stellate cells, resulting in increased delivery of its substrate antioxidant ERGO and a protective effect against liver fibrosis. PMID:27020986

  5. The effect of 48-hour fasting on taurine status in healthy adult dogs.

    PubMed

    Gray, K; Alexander, L G; Staunton, R; Colyer, A; Watson, A; Fascetti, A J

    2016-06-01

    Low circulating taurine concentrations may be a risk factor for dilated cardiomyopathy (DCM) in dogs. Circulating taurine is typically measured in the clinic 4-5 h after feeding, largely because the impact of later sampling is not known. The objective of this study was to measure taurine in the blood during a 48-h fast in 12 healthy adult Labrador Retrievers to refine sampling methodology for determination of taurine status. Plasma and whole blood (WB) taurine concentrations did not fall to levels indicative of clinical deficiency throughout fasting; WB was the more reliable indicator of taurine status. This study shows that blood samples can be taken for assessment of taurine status any time up to 48 h after ingestion of a meal in healthy adult dogs. PMID:26250395

  6. Impact of processing on the taurine content in processed seafood and their corresponding unprocessed raw materials.

    PubMed

    Dragnes, Bjørn T; Larsen, Rune; Ernstsen, Marita Holm; Mæhre, Hanne; Elvevoll, Edel O

    2009-03-01

    Processing of foods can lead to losses of water-soluble components, and some of these may have beneficial health effects. Taurine has lately attracted attention due to its suggested strong contribution to the health-promoting effects of seafood. The lack of systematic information on the content of conditionally essential nutrients, such as taurine, has led to this study. The taurine concentrations in a variety of common marine dinners and spreads, and their corresponding raw materials, have been determined. Losses of taurine in processed products ranged up to 100% when compared with the taurine content of freshly caught specimens. Products soaked in brines or products subjected to rough processing conditions such as mincing and washing had greater loss compared with products with more intact muscle. Levels of taurine in processed seafood vary according to product type and brand, showing a potential for the industry to take measures in preventing losses of taurine and other water-soluble components. PMID:18608559

  7. Multidrug ATP-binding cassette transporters are essential for hepatic development of Plasmodium sporozoites.

    PubMed

    Rijpma, Sanna R; van der Velden, Maarten; González-Pons, Maria; Annoura, Takeshi; van Schaijk, Ben C L; van Gemert, Geert-Jan; van den Heuvel, Jeroen J M W; Ramesar, Jai; Chevalley-Maurel, Severine; Ploemen, Ivo H; Khan, Shahid M; Franetich, Jean-Francois; Mazier, Dominique; de Wilt, Johannes H W; Serrano, Adelfa E; Russel, Frans G M; Janse, Chris J; Sauerwein, Robert W; Koenderink, Jan B; Franke-Fayard, Blandine M

    2016-03-01

    Multidrug resistance-associated proteins (MRPs) belong to the C-family of ATP-binding cassette (ABC) transport proteins and are known to transport a variety of physiologically important compounds and to be involved in the extrusion of pharmaceuticals. Rodent malaria parasites encode a single ABC transporter subfamily C protein, whereas human parasites encode two: MRP1 and MRP2. Although associated with drug resistance, their biological function and substrates remain unknown. To elucidate the role of MRP throughout the parasite life cycle, Plasmodium berghei and Plasmodium falciparum mutants lacking MRP expression were generated. P. berghei mutants lacking expression of the single MRP as well as P. falciparum mutants lacking MRP1, MRP2 or both proteins have similar blood stage growth kinetics and drug-sensitivity profiles as wild type parasites. We show that MRP1-deficient parasites readily invade primary human hepatocytes and develop into mature liver stages. In contrast, both P. falciparum MRP2-deficient parasites and P. berghei mutants lacking MRP protein expression abort in mid to late liver stage development, failing to produce mature liver stages. The combined P. berghei and P. falciparum data are the first demonstration of a critical role of an ABC transporter during Plasmodium liver stage development. PMID:26332724

  8. Effects of chronic kidney disease and uremia on hepatic drug metabolism and transport.

    PubMed

    Yeung, Catherine K; Shen, Danny D; Thummel, Kenneth E; Himmelfarb, Jonathan

    2014-03-01

    The pharmacokinetics of non-renally cleared drugs in patients with chronic kidney disease is often unpredictable. Some of this variability may be due to alterations in the expression and activity of extra renal drug-metabolizing enzymes and transporters, primarily localized in the liver and intestine. Studies conducted in rodent models of renal failure have shown decreased mRNA and protein expression of many members of the cytochrome P450 enzyme (CYP) gene family and the ATP-binding cassette (ABC) and solute carrier (SLC) gene families of drug transporters. Uremic toxins interfere with transcriptional activation, cause downregulation of gene expression mediated by proinflammatory cytokines, and directly inhibit the activity of the cytochrome P450s and drug transporters. While much has been learned about the effects of kidney disease on non-renal drug disposition, important questions remain regarding the mechanisms of these effects, as well as the interplay between drug-metabolizing enzymes and drug transporters in the uremic milieu. In this review, we have highlighted the existing gaps in our knowledge and understanding of the impact of chronic kidney disease on non-renal drug clearance, and identified areas of opportunity for future research. PMID:24132209

  9. Ontogeny of Hepatic Drug Transporters and Relevance to Drugs Used in Pediatrics.

    PubMed

    Elmorsi, Yasmine; Barber, Jill; Rostami-Hodjegan, Amin

    2016-07-01

    Most of the pharmacokinetic studies conducted to calculate pediatric drug doses are based on scaling from adult data using various allometric parameters related to body size. However, these uniform scaling methods cannot account for all physiologic changes occurring during maturation, which influence various drugs in different ways. The ontogeny of physiologic and biologic functions accompanying the progression from infancy to childhood to adulthood does not proceed in a simple monotonic rate with body size for various elimination pathways. The transporters and their interplay with enzymes have a substantial role in drug metabolism and disposition. Although much is known about enzymes and their ontogeny, there is a scarcity of information on the ontogenic profile of drug transporters, particularly during the early years of human life. These ontogeny data are required for the enhancement of physiologically based pharmacokinetic models, and consequently for the prediction of pharmacokinetic profiles of new therapeutic compounds in pediatric populations. This review points to the relative ontogeny rate for enzymes and transporters and how these may confound our understanding of the role that transporters may or may not play in childhood compared with adulthood. PMID:26712821

  10. Kinetics for the synthetic bile acid 75-selenohomocholic acid-taurine in humans: comparison with (/sup 14/C)taurocholate

    SciTech Connect

    Jazrawi, R.P.; Ferraris, R.; Bridges, C.; Northfield, T.C.

    1988-07-01

    The apparent fractional turnover rate of the gamma-labeled bile acid analogue 75-selenohomocholic acid-taurine (75-SeHCAT) was assessed from decline in radioactivity over the gallbladder area on 4 successive days using a gamma-camera, and was compared in the same subjects with the fractional turnover rate of the corresponding natural bile acid, cholic acid-taurine, labeled with 14C ((14C)CAT) using the classical Lindstedt technique. Very similar results were obtained in 5 healthy individuals (coefficient of variation 4.8%, medians 0.35 and 0.34, respectively). By contrast, the fractional deconjugation rate assessed from zonal scanning of glycine- and taurine-conjugated bile acids on thin-layer chromatography was much less for 75-SeHCAT than for (14C)CAT (0.02 and 0.13, respectively; p less than 0.05). The fractional rate for deconjugation plus dehydroxylation was also determined by zonal scanning, and gave lower values for 75-SeHCAT than for (14C)CAT (0.02 and 0.12, respectively; p less than 0.05). There was a striking similarity between the fractional rate for deconjugation alone and that for deconjugation plus dehydroxylation for both bile acids in individual samples (r = 0.999, p less than 0.001), suggesting that these two processes might occur simultaneously and probably involve the same bacteria. We conclude that our scintiscanning technique provides an accurate, noninvasive method of measuring fractional turnover rate of a bile acid in humans, and that the finding that 75SeHCAT remains conjugated with taurine during enterohepatic recycling means that absorption should be specific for the ileal active transport site, thus rendering it an ideal substance for assessing ileal function.

  11. Activity-dependent endogenous taurine release facilitates excitatory neurotransmission in the neocortical marginal zone of neonatal rats

    PubMed Central

    Qian, Taizhe; Chen, Rongqing; Nakamura, Masato; Furukawa, Tomonori; Kumada, Tatsuro; Akita, Tenpei; Kilb, Werner; Luhmann, Heiko J.; Nakahara, Daiichiro; Fukuda, Atsuo

    2014-01-01

    In the developing cerebral cortex, the marginal zone (MZ), consisting of early-generated neurons such as Cajal-Retzius cells, plays an important role in cell migration and lamination. There is accumulating evidence of widespread excitatory neurotransmission mediated by γ-aminobutyric acid (GABA) in the MZ. Cajal-Retzius cells express not only GABAA receptors but also α2/β subunits of glycine receptors, and exhibit glycine receptor-mediated depolarization due to high [Cl−]i. However, the physiological roles of glycine receptors and their endogenous agonists during neurotransmission in the MZ are yet to be elucidated. To address this question, we performed optical imaging from the MZ using the voltage-sensitive dye JPW1114 on tangential neocortical slices of neonatal rats. A single electrical stimulus evoked an action-potential-dependent optical signal that spread radially over the MZ. The amplitude of the signal was not affected by glutamate receptor blockers, but was suppressed by either GABAA or glycine receptor antagonists. Combined application of both antagonists nearly abolished the signal. Inhibition of Na+, K+-2Cl− cotransporter by 20 µM bumetanide reduced the signal, indicating that this transporter contributes to excitation. Analysis of the interstitial fluid obtained by microdialysis from tangential neocortical slices with high-performance liquid chromatography revealed that GABA and taurine, but not glycine or glutamate, were released in the MZ in response to the electrical stimulation. The ambient release of taurine was reduced by the addition of a voltage-sensitive Na+ channel blocker. Immunohistochemistry and immunoelectron microscopy indicated that taurine was stored both in Cajal-Retzius and non-Cajal-Retzius cells in the MZ, but was not localized in presynaptic structures. Our results suggest that activity-dependent non-synaptic release of endogenous taurine facilitates excitatory neurotransmission through activation of glycine receptors in

  12. Interactions of taurine and structurally related analogues with the GABAergic system and taurine binding sites of rabbit brain

    PubMed Central

    Frosini, Maria; Sesti, Casilde; Dragoni, Stefania; Valoti, Massimo; Palmi, Mitri; Dixon, Henry B F; Machetti, Fabrizio; Sgaragli, Giampietro

    2003-01-01

    The aim of this study was to find taurinergic compounds that do not interact with brain GABA ergic systems. Washed synaptic membranes (SM) from whole rabbit brain were able to bind [3H]muscimol. Saturation experiments of the binding of [3H]GABA to GABAB receptors showed that SM possess two binding components; twice Triton X-100-treated SM contained 0.048 mmol endogenous taurine/kg protein and bound [3H]taurine in a saturable manner (Kd=249.0±6.3 nM and Bmax=3.4±1.0 pmol mg−1 prot). Among the 19 structural analogues of taurine, 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2-hydroxyethanesulfonic (ISE) and (±)cis-2-aminocyclohexane sulfonic acids (CAHS) displaced [3H]taurine binding (Ki=0.13, 0.13, 13.5 and 4.0 μM, respectively). These analogues did not interact with GABAA and GABAB receptors and did not affect taurine- and GABA-uptake systems and GABA-transaminase activity. 3-Aminopropanesulfonic acid (OMO), β-alanine, pyridine-3-sulfonic acid, N,N,N-trimethyltaurine (TMT), 2-(guanidino)ethanesulfonic acid (GES), ethanolamine-O-sulphate, N,N-dimethyltaurine (DMT), taurine and (±)piperidine-3-sulfonic acid (PSA) inhibited [3H]muscimol binding to GABAA receptors with different affinities (Ki=0.013, 7.9, 24.6, 47.5, 52.0, 91.0, 47.5, 118.1 and 166.3 μM, respectively). Taurine, 2-aminoethylphosphonic acid, DMT, TMT and OMO inhibited the binding of [3H]GABA to GABAB receptors with Ki's in the μM range (0.8, 3.5, 4.4, 11.3 and 5.0, respectively). GES inhibited taurine uptake (IC50=3.72 μM) and PSA GABA transaminase activity (IC50=103.0 μM). In conclusion, AEA, TAG, ISE and CAHS fulfill the criteria for taurinergic agents. PMID:12684273

  13. Transport, metabolism, and effect of chronic feeding of lagodeoxycholic acid. A new, natural bile acid.

    PubMed

    Schmassmann, A; Angellotti, M A; Clerici, C; Hofmann, A F; Ton-Nu, H T; Schteingart, C D; Marcus, S N; Hagey, L R; Rossi, S S; Aigner, A

    1990-10-01

    Ursodeoxycholic acid, the 7 beta-hydroxy epimer of chenodeoxycholic acid, is more hydrophilic and less hepatotoxic than chenodeoxycholic acid. Because "lagodeoxycholic acid," the 12 beta-hydroxy epimer of deoxycholic acid, is also more hydrophilic than deoxycholic acid, it was hypothesized that it should also be less hepatotoxic than deoxycholic acid. To test this, lagodeoxycholic acid was synthesized, and its transport and metabolism were examined in the rat, rabbit, and hamster. The taurine conjugate of lagodeoxycholic acid was moderately well transported by the perfused rat ileum (Tmax = 2 mumol/min.kg). In rats and hamsters with biliary fistulas, the taurine conjugate of lagodeoxycholic acid was well transported by the liver with a Tmax greater than 20 mumol/min.kg; for the taurine conjugate of deoxycholic acid, doses infused at a rate greater than 2.5 mumol/min.kg are known to cause cholestasis and death. Hepatic biotransformation of lagodeoxycholic acid in the rabbit was limited to conjugation with glycine; in the hamster, lagodeoxycholic acid was conjugated with glycine or taurine; in addition, 7-hydroxylation occurred to a slight extent (approximately 10%). When lagodeoxycholic acid was instilled in the rabbit colon, it was absorbed as such although within hours it was progressively epimerized by bacteria to deoxycholic acid. When injected intravenously and allowed to circulate enterohepatically, lagodeoxycholic acid was largely epimerized to deoxycholic acid in 24 hours. Surgical creation of a distal ileostomy abolished epimerization in the rabbit, indicating that exposure to colonic bacterial enzymes was required for the epimerization. Lagodeoxycholic acid was administered for 3 weeks at a dose of 180 mumol/day (0.1% by weight of a chow diet; 2-4 times the endogenous bile acid synthesis rate); other groups received identical doses of deoxycholic acid (hamster) or cholyltaurine, a known precursor of deoxycholic acid (rabbit). After 3 weeks of

  14. Diurnal Variations of Mouse Plasma and Hepatic Bile Acid Concentrations as well as Expression of Biosynthetic Enzymes and Transporters

    PubMed Central

    Zhang, Yu-Kun Jennifer; Guo, Grace L.; Klaassen, Curtis D.

    2011-01-01

    Background Diurnal fluctuation of bile acid (BA) concentrations in the enterohepatic system of mammals has been known for a long time. Recently, BAs have been recognized as signaling molecules beyond their well-established roles in dietary lipid absorption and cholesterol homeostasis. Methods and Results The current study depicted diurnal variations of individual BAs detected by ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) in serum and livers collected from C57BL/6 mice fed a regular chow or a chow containing cholestyramine (resin). Circadian rhythms of mRNA of vital BA-related nuclear receptors, enzymes, and transporters in livers and ilea were determined in control- and resin-fed mice, as well as in farnesoid X receptor (FXR) null mice. The circadian profiles of BAs showed enhanced bacterial dehydroxylation during the fasting phase and efficient hepatic reconjugation of BAs in the fed phase. The resin removed more than 90% of BAs with β-hydroxy groups, such as muricholic acids and ursodeoxycholic acid, from serum and livers, but did not exert as significant influence on CA and CDCA in both compartments. Both resin-fed and FXR-null mouse models indicate that BAs regulate their own biosynthesis through the FXR-regulated ileal fibroblast growth factor 15. BA flux also influences the daily mRNA levels of multiple BA transporters. Conclusion BA concentration and composition exhibit circadian variations in mouse liver and serum, which influences the circadian rhythms of BA metabolizing genes in liver and ileum. The diurnal variations of BAs appear to serve as a signal that coordinates daily nutrient metabolism in mammals. PMID:21346810

  15. Endogenous N-acyl taurines regulate skin wound healing.

    PubMed

    Sasso, Oscar; Pontis, Silvia; Armirotti, Andrea; Cardinali, Giorgia; Kovacs, Daniela; Migliore, Marco; Summa, Maria; Moreno-Sanz, Guillermo; Picardo, Mauro; Piomelli, Daniele

    2016-07-26

    The intracellular serine amidase, fatty acid amide hydrolase (FAAH), degrades a heterogeneous family of lipid-derived bioactive molecules that include amides of long-chain fatty acids with taurine [N-acyl-taurines (NATs)]. The physiological functions of the NATs are unknown. Here we show that genetic or pharmacological disruption of FAAH activity accelerates skin wound healing in mice and stimulates motogenesis of human keratinocytes and differentiation of human fibroblasts in primary cultures. Using untargeted and targeted lipidomics strategies, we identify two long-chain saturated NATs-N-tetracosanoyl-taurine [NAT(24:0)] and N-eicosanoyl-taurine [NAT(20:0)]-as primary substrates for FAAH in mouse skin, and show that the levels of these substances sharply decrease at the margins of a freshly inflicted wound to increase again as healing begins. Additionally, we demonstrate that local administration of synthetic NATs accelerates wound closure in mice and stimulates repair-associated responses in primary cultures of human keratinocytes and fibroblasts, through a mechanism that involves tyrosine phosphorylation of the epidermal growth factor receptor and an increase in intracellular calcium levels, under the permissive control of transient receptor potential vanilloid-1 receptors. The results point to FAAH-regulated NAT signaling as an unprecedented lipid-based mechanism of wound-healing control in mammalian skin, which might be targeted for chronic wound therapy. PMID:27412859

  16. Occurrence of a taurine derivative in an antarctic glass sponge.

    PubMed

    Carbone, Marianna; Núñez-Pons, Laura; Ciavatta, M Letizia; Castelluccio, Francesco; Avila, Conxita; Gavagnin, Margherita

    2014-04-01

    The n-butanol extract of an Antarctic hexactinellid sponge, Anoxycalyx (Scolymastra) joubini, was found to contain a taurine-conjugated anthranilic acid, never reported so far either as a natural product or by synthesis. The compound was inactive against human cancer cells in an in vitro growth inhibitory test, and also showed no antibacterial activity. PMID:24868857

  17. Role of taurine in the pathologies of MELAS and MERRF.

    PubMed

    Schaffer, Stephen W; Jong, Chian Ju; Ito, Takashi; Azuma, Junichi

    2014-01-01

    Taurine is an abundant β-amino acid that concentrates in the mitochondria, where it participates in the conjugation of tRNAs for leucine, lysine, glutamate and glutamine. The formation of 5-taurinomethyluridine-tRNA strengthens the interaction of the anticodon with the codon, thereby promoting the decoding of several codons, including those for AAG, UUG, CAG and GAG. By preventing these series of events, taurine deficiency appears to diminish the formation of 5-taurinomethyluridine and causes inefficient decoding for the mitochondrial codons of leucine, lysine, glutamate and glutamine. The resulting reduction in the biosynthesis of mitochondria-encoded proteins deprives the respiratory chain of subunits required for the assembly of respiratory chain complexes. Hence, taurine deficiency is associated with a reduction in oxygen consumption, an elevation in glycolysis and lactate production and a decline in ATP production. A similar sequence of events takes place in mitochondrial diseases MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged-red fiber syndrome). In both diseases, mutations in their respective tRNAs interfere with the formation of 5-taurinomethyluridine in the wobble position. Hence, the taurine-deficient phenotype resembles the phenotypes of MELAS and MERRF. PMID:23179085

  18. Cadmium induced testicular pathophysiology: prophylactic role of taurine.

    PubMed

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C

    2008-01-01

    The aim of the present study was to investigate the role of taurine against cadmium induced testicular pathophysiology. Cadmium (in the form of Cadmium chloride, CdCl(2)) administration at a dose of 4 mg/kg body weight for 6 days significantly decreased testicular Delta(5)-3beta-HSD and 17beta-HSD activities along with the reduction in the plasma testosterone level. In addition, reductions in testicular sperm count as well as loss in sperm motility were also observed in Cd-intoxication. Cd increased the intracellular concentration of reactive oxygen species and testicular Cd accumulation. Besides, increased levels of lipid peroxidation, protein carbonylation, glutathione disulfide and DNA fragmentation as well as decreased levels of the activities of the antioxidant enzymes, total thiols and reduced glutathione were also found to be associated with this toxicity. Taurine pretreatment at a dose of 100 mg/kg body weight for 5 days, on the other hand, could prevent all the Cd-induced testicular pathophysiology and oxidative insult related studied parameters. Taurine treatment, in addition also increased the in vivo ferric reducing antioxidant power linearly up to a dose of 100 mg/kg body weight. Histological examination of testicular sections from experimental animals supported these results. The effect of a well established antioxidant, vitamin C has been included in the study as a positive control. Combining all, data suggest that being an antioxidant, taurine plays a beneficial role against Cd-induced adverse effects on the male reproductive system. PMID:18926901

  19. Utility of bilirubins and bile acids as endogenous biomarkers for the inhibition of hepatic transporters.

    PubMed

    Watanabe, Tomoko; Miyake, Manami; Shimizu, Toshinobu; Kamezawa, Miho; Masutomi, Naoya; Shimura, Takesada; Ohashi, Rikiya

    2015-04-01

    It is useful to identify endogenous substrates for the evaluation of drug-drug interactions via transporters. In this study, we investigated the utility of bilirubins, substrates of OATPs and MRP2, and bile acids and substrates of NTCP and BSEP, as biomarkers for the inhibition of transporters. In rats administered 20 and 80 mg/kg rifampicin, the plasma levels of bilirubin glucuronides were elevated, gradually decreased, and almost returned to the baseline level at 24 hours after administration without an elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). This result indicates the transient inhibition of rOatps and/or rMrp2. Although the correlation between free plasma concentrations and IC50 values of rOatps depended on the substrates used in the in vitro studies, the inhibition of rOatps by rifampicin was confirmed in the in vivo study using valsartan as a substrate of rOatps. In rats administered 10 and 30 mg/kg cyclosporin A, the plasma levels of bile acids were elevated and persisted for up to 24 hours after administration without an elevation of ALT and AST. This result indicates the continuous inhibition of rNtcp and/or rBsep, although there were differences between the free plasma or liver concentrations and IC50 values of rNtcp or rBsep, respectively. This study suggests that the monitoring of bilirubins and bile acids in plasma is useful in evaluating the inhibitory potential of their corresponding transporters. PMID:25581390

  20. Eletriptan metabolism by human hepatic CYP450 enzymes and transport by human P-glycoprotein.

    PubMed

    Evans, David C; O'Connor, Desmond; Lake, Brian G; Evers, Raymond; Allen, Christopher; Hargreaves, Richard

    2003-07-01

    "Reaction phenotyping" studies were performed with eletriptan (ETT) to determine its propensity to interact with coadministered medications. Its ability to serve as a substrate for human P-glycoprotein (P-gp) was also investigated since a central mechanism of action has been proposed for this "triptan" class of drug. In studies with a characterized bank of human liver microsome preparations, a good correlation (r2 = 0.932) was obtained between formation of N-desmethyl eletriptan (DETT) and CYP3A4-catalyzed testosterone 6 beta-hydroxylation. DETT was selected to be monitored in our studies since it represents a significant ETT metabolite in humans, circulating at concentrations 10 to 20% of those observed for parent drug. ETT was metabolized to DETT by recombinant CYP2D6 (rCYP2D6) and rCYP3A4, and to a lesser extent by rCYP2C9 and rCYP2C19. The metabolism of ETT to DETT in human liver microsomes was markedly inhibited by troleandomycin, erythromycin, miconazole, and an inhibitory antibody to CYP3A4, but not by inhibitors of other major P450 enzymes. ETT had little inhibitory effect on any of the P450 enzymes investigated. ETT was determined to be a good substrate for human P-gp in vitro. In bidirectional transport studies across LLC-MDR1 and LLC-Mdr1a cell monolayers, ETT had a BA/AB transport ratio in the range 9 to 11. This finding had significance in vivo since brain exposure to ETT was reduced 40-fold in Mdr1a+/+ relative to Mdr1a-/- mice. ETT metabolism to DETT is therefore catalyzed primarily by CYP3A4, and plasma concentrations are expected to be increased when coadministered with inhibitors of CYP3A4 and P-gp activity. PMID:12814962

  1. Viral Hepatitis

    MedlinePlus

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  2. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  3. Taurine content in different brain structures during ageing: effect on hippocampal synaptic plasticity.

    PubMed

    Suárez, Luz M; Muñoz, María-Dolores; Martín Del Río, Rafael; Solís, José M

    2016-05-01

    A reduction in taurine content accompanies the ageing process in many tissues. In fact, the decline of brain taurine levels has been associated with cognitive deficits whereas chronic administration of taurine seems to ameliorate age-related deficits such as memory acquisition and retention. In the present study, using rats of three age groups (young, adult and aged) we determined whether the content of taurine and other amino acids (glutamate, serine, glutamine, glycine, alanine and GABA) was altered during ageing in different brain areas (cerebellum, cortex and hippocampus) as well non-brain tissues (heart, kidney, liver and plasma). Moreover, using hippocampal slices we tested whether ageing affects synaptic function and plasticity. These parameters were also determined in aged rats fed with either taurine-devoid or taurine-supplemented diets. With age, we found heterogeneous changes in amino acid content depending on the amino acid type and the tissue. In the case of taurine, its content was reduced in the cerebellum of adult and aged rats, but it remained unchanged in the hippocampus, cortex, heart and liver. The synaptic response amplitude decreased in aged rats, although the late phase of long-term synaptic potentiation (late-LTP), a taurine-dependent process, was not altered. Our study highlights the stability of taurine content in the hippocampus during ageing regardless of whether taurine was present in the diet, which is consistent with the lack of changes detected in late-LTP. These results indicate that the beneficial effects of taurine supplementation might be independent of the replenishment of taurine stores. PMID:26803657

  4. Neuroprotection by taurine in ethanol-induced apoptosis in the developing cerebellum

    PubMed Central

    2010-01-01

    Background Acute ethanol administration leads to massive apoptotic neurodegeneration in the developing central nervous system. We studied whether taurine is neuroprotective in ethanol-induced apoptosis in the mouse cerebellum during the postnatal period. Methods The mice were divided into three groups: ethanol-treated, ethanol+taurine-treated and controls. Ethanol (20% solution) was administered subcutaneously at a total dose of 5 g/kg (2.5 g/kg at time 1 h and 2.5 g/kg at 3 h) to the ethanol and ethanol+taurine groups. The ethanol+taurine group also received two injections of taurine (1 g/kg each, at time zero and at 4 h). To estimate apoptosis, immunostaining for activated caspase-3 and TUNEL staining were made in the mid-sagittal sections containing lobules I-X of the cerebellar vermis at 12 or 8 hours after the first taurine injection. Changes in the blood taurine level were monitored at each hour by reverse-phase high-performance liquid chromatography (HPLC). Results Ethanol administration induced apoptosis of Purkinje cells on P4 in all cerebellar lobules, most extensively in lobules IX and X, and on P7 increased the number of activated caspase-3-immunoreactive and TUNEL-positive cells in the internal layer of the cerebellum. Administration of taurine significantly decreased the number of activated caspase-3-immunoreactive and TUNEL-positive cells in the internal layer of the cerebellum on P7, but had no effect on Purkinje cells in P4 mice. The high initial taurine concentration in blood of the ethanol+taurine group diminished dramatically during the experiment, not being different at 13 h from that in the controls. Conclusions We conclude that the neuroprotective action of taurine is not straightforward and seems to be different in different types of neurons and/or requires prolonged maintenance of the high taurine concentration in blood plasma. PMID:20804586

  5. Isolation and derivatization of plasma taurine for stable isotope analysis by gas chromatography-mass spectrometry

    SciTech Connect

    Irving, C.S.; Klein, P.D.

    1980-09-01

    A method for the isolation and derivatization of plasma taurine is described that allows stable isotope determinations of taurine to be made by gas chromatography-mass spectrometry. The isolation procedure can be applied to 0.1 ml of plasma; the recovery of plasma taurine was 70 to 80%. For gc separation, taurine was converted to its dimethylaminomethylene methyl ester derivative which could not be detected by hydrogen flame ionization, but could be monitored readily by NH/sub 3/ chemical ionization mass spectrometry. The derivatization reaction occurred partially on-column and required optimization of injection conditions. Using stable isotope ratiometry multiple ion detection, (M + 2 + H)/sup +//(M + H)/sup +/ ion ratio of natural abundance taurine was determined with a standard deviation of less than +-0.07% of the ratio. The (1,2-/sup 13/C)taurine/taurine mole ratios of standard mixtures could be accurately determined to 0.001. This stable isotope gc-ms method is suitable for studying the plasma kinetics of (1,2-/sup 13/C)taurine in infants who are at risk with respect to taurine depletion.

  6. Development of a Novel Cysteine Sulfinic Acid Decarboxylase Knockout Mouse: Dietary Taurine Reduces Neonatal Mortality

    PubMed Central

    Park, Eunkyue; Park, Seung Yong; Schuller-Levis, Georgia

    2014-01-01

    We engineered a CSAD KO mouse to investigate the physiological roles of taurine. The disruption of the CSAD gene was verified by Southern, Northern, and Western blotting. HPLC indicated an 83% decrease of taurine concentration in the plasma of CSAD−/−. Although CSAD−/− generation (G)1 and G2 survived, offspring from G2 CSAD−/− had low brain and liver taurine concentrations and most died within 24 hrs of birth. Taurine concentrations in G3 CSAD−/− born from G2 CSAD−/− treated with taurine in the drinking water were restored and survival rates of G3 CSAD−/− increased from 15% to 92%. The mRNA expression of CDO, ADO, and TauT was not different in CSAD−/− compared to WT and CSAD mRNA was not expressed in CSAD−/−. Expression of Gpx 1 and 3 was increased significantly in CSAD−/− and restored to normal levels with taurine supplementation. Lactoferrin and the prolactin receptor were significantly decreased in CSAD−/−. The prolactin receptor was restored with taurine supplementation. These data indicated that CSAD KO is a good model for studying the effects of taurine deficiency and its treatment with taurine supplementation. PMID:24639894

  7. Taurine Induces Proliferation of Neural Stem Cells and Synapse Development in the Developing Mouse Brain

    PubMed Central

    Shivaraj, Mattu Chetana; Marcy, Guillaume; Low, Guoliang; Ryu, Jae Ryun; Zhao, Xianfeng; Rosales, Francisco J.; Goh, Eyleen L. K.

    2012-01-01

    Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems. PMID:22916184

  8. Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism.

    PubMed

    Shao, Xue; Hu, Zhengtao; Hu, Chunyan; Bu, Qian; Yan, Guangyan; Deng, Pengchi; Lv, Lei; Wu, Dan; Deng, Yi; Zhao, Jinxuan; Zhu, Ruiming; Li, Yan; Li, Hongyu; Xu, Youzhi; Yang, Hanshuo; Zhao, Yinglan; Cen, Xiaobo

    2012-05-01

    Investigations have characterized addictive drug-induced developmental cardiovascular malformation in human, non-human primate and rodent. However, the underlying mechanism of malformation caused by drugs during pregnancy is still largely unknown, and preventive and therapeutic measures have been lacking. Using 1H NMR spectroscopy, we profiled the metabolites from human embryo endothelial cells exposed to methamphetamine (METH) and quantified a total of 226 peaks. We identified 11 metabolites modified robustly and found that taurine markedly increased. We then validated the hypothesis that this dramatic increase in taurine could attribute to its effect in inhibiting METH-induced developmental angiogenesis defect. Taurine supplement showed a more significant potential than other metabolites in protecting against METH-induced injury in endothelial cells. Taurine strongly attenuated METH-induced inhibition of proliferation and migration in endothelial cells. Furthermore, death rate and vessel abnormality of zebrafish embryos treated with METH were greatly reversed by taurine. In addition, taurine supplement caused a rapid decrease in reactive oxygen species generation and strongly attenuated the excitable arise of antioxidase activities in the beginning of METH exposure prophase. Dysregulations of NF-κB, p-ERK as well as Bax, which reflect apoptosis, cell cycle arrest and oxidative stress in vascular endothelium, were blocked by taurine. Our results provide the first evidence that taurine prevents METH-caused developmental angiogenesis defect through antioxidant mechanism. Taurine could serve as a potential therapeutic or preventive intervention of developmental vascular malformation for the pregnant women with drug use. PMID:22426360

  9. Inhibition of hepatic organic anion-transporting polypeptide by RNA interference in sandwich-cultured human hepatocytes: an in vitro model to assess transporter-mediated drug-drug interactions.

    PubMed

    Liao, Mingxiang; Raczynski, Arek R; Chen, Michael; Chuang, Bei-Ching; Zhu, Qing; Shipman, Rob; Morrison, Jodi; Lee, David; Lee, Frank W; Balani, Suresh K; Xia, Cindy Q

    2010-09-01

    Organic anion-transporting polypeptides (OATPs), members of the SLCO/SLC21 family, mediate the transport of various endo- and xenobiotics. In human liver, OATP1B1, 1B3, and 2B1 are located at the basolateral membrane of hepatocytes and are involved in hepatic drug uptake and biliary elimination. Clinically significant drug-drug interactions (DDIs) mediated by hepatic OATPs have drawn great attention from clinical practitioners and researchers. However, there are considerable challenges to prospectively understanding the extent of OATP-mediated DDIs because of the lack of specific OATP inhibitors or substrates and the limitations of in vitro tools. In the present study, a novel RNA interference knockdown sandwich-cultured human hepatocyte model was developed and validated. Quantitative polymerase chain reaction, microarray and immunoblotting analyses, along with uptake assays, illustrated that the expression and transport activity of hepatic OATPs were reduced by small interfering (siRNA) efficiently and specifically in this model. Although OATP siRNA decreased only 20 to 30% of the total uptake of cerivastatin into human hepatocytes, it caused a 50% reduction in cerivastatin metabolism, which was observed by monitoring the formation of the two major metabolites of cerivastatin. The results suggest that coadministration of a drug that is a hepatic OATP inhibitor could significantly alter the pharmacokinetic profile of cerivastatin in clinical studies. Further studies with this novel model demonstrated that OATP and cytochrome P450 have a synergistic effect on cerivastatin-gemfibrozil interactions. The siRNA knockdown sandwich-cultured human hepatocytes may provide a new powerful model for evaluating DDIs. PMID:20516252

  10. Conformational Study of Taurine in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Cortijo, Vanessa; Sanz, M. Eugenia; López, Juan C.; Alonso, José L.

    2009-08-01

    The conformational preferences of the amino sulfonic acid taurine (NH2-CH2-CH2-SO3H) have been investigated in the gas phase by laser ablation molecular beam Fourier transform microwave spectroscopy (LA-MB-FTMW) in the 6-14 GHz frequency range. One conformer has been observed, and its rotational, centrifugal distortion, and hyperfine quadrupole coupling constants have been determined from the analysis of its rotational spectrum. Comparison of the experimental constants with those calculated theoretically identifies the detected conformer unambiguously. The observed conformer of taurine is stabilized by an intramolecular hydrogen bond O-H···N between the hydrogen of the sulfonic acid group and the nitrogen atom of the amino group.

  11. Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation.

    PubMed

    Hussy, N; Deleuze, C; Pantaloni, A; Desarménien, M G; Moos, F

    1997-08-01

    1. To evaluate the implication of taurine in the physiology of supraoptic neurones, we (i) investigated the agonist properties of taurine on glycine and GABAA receptors of supraoptic magnocellular neurones acutely dissociated from adult rats, using whole-cell voltage clamp, (ii) studied the effects of taurine and strychnine in vivo by extracellular recordings of supraoptic vasopressin neurones in anaesthetized rats, and (iii) measured the osmolarity-dependent release of endogenous taurine from isolated supraoptic nuclei by HPLC. 2. GABA, glycine and taurine evoked rapidly activating currents that all reversed close to the equilibrium potential for Cl-, indicating activation of Cl(-)-selective channels. Glycine-activated currents were reversibly blocked by strychnine (IC50 of 35 nM with 100 microM glycine), but were unaffected by the GABAA antagonist gabazine (1-3 microM). GABA-activated currents were reversibly antagonized by 3 microM gabazine, but not by strychnine (up to 1 microM). 3. Responses to 1 mM taurine were blocked by strychnine but not by gabazine and showed no additivity with glycine-induced currents, indicating selective activation of glycine receptors. Responses to 10 mM taurine were partially antagonized by gabazine, the residual current being blocked by strychnine. Thus, taurine is also a weak agonist of GABAA receptors. 4. In the presence of gabazine, taurine activated glycine receptors with an EC50 of 406 microM. Taurine activated at most 70% of maximal glycine currents, suggesting that it is a partial agonist of glycine receptors. 5. In vivo, locally applied strychnine (300 nM) increased and taurine (1 mM) decreased the basal electrical activity of vasopressin neurones in normally hydrated rats. The effect of strychnine was markedly more pronounced in water-loaded rats. 6. Taurine, which is concentrated in supraoptic glial cells, could be released from isolated supraoptic nuclei upon hyposmotic stimulation. Decreases in osmolarity of 15 and 30

  12. The effect of insulin on plasma glucose concentrations, expression of hepatic glucose transporters and key gluconeogenic enzymes during the perinatal period in broiler chickens.

    PubMed

    Franssens, Lies; Lesuisse, Jens; Wang, Yufeng; Willems, Els; Willemsen, Hilke; Koppenol, Astrid; Guo, Xiaoquan; Buyse, Johan; Decuypere, Eddy; Everaert, Nadia

    2016-06-01

    Chickens have blood glucose concentrations that are twofold higher than those observed in mammals. Moreover, the insulin sensitivity seems to decrease with postnatal age in both broiler and layer chickens. However, little is known about the response of insulin on plasma glucose concentrations and mRNA abundance of hepatic glucose transporters 1, 2, 3, 8, 9 and 12 (GLUT1, 2, 3, 8, 9 and 12) and three regulatory enzymes of the gluconeogenesis, phosphoenolpyruvate carboxykinase 1 and 2 (PCK1 and 2) or fructose-1,6-biphosphatase 1 (FBP1) in chicks during the perinatal period. In the present study, broiler embryos on embryonic day (ED)16, ED18 or newly-hatched broiler chicks were injected intravenously with bovine insulin (1μg/g body weight (BW)) to examine plasma glucose response and changes in hepatic mRNA abundance of the GLUTs, PCK1 and 2 and FBP1. Results were compared with a non-treated control group and a saline-injected sham group. Plasma glucose levels of insulin-treated ED18 embryos recovered faster from their minimum level than those of insulin-treated ED16 embryos or newly-hatched chicks. In addition, at the minimum plasma glucose level seven hours post-injection (PI), hepatic GLUT2, FBP1 and PCK2 mRNA abundance was decreased in insulin-injected embryos, compared to sham and control groups, being most pronounced when insulin injection occurred on ED16. PMID:26723190

  13. Effect of dietary taurine supplementation on growth, feed efficiency, and nutrient composition of juvenile sablefish (Anoplopoma fimbria)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Juvenile sablefish were fed a low taurine, basal feed with seven graded levels of supplemental taurine to determine taurine requirements for growth and feed efficiency. The basal feed was plant based, formulated primarily with soy and corn proteins with a minimal (9%) amount of fishmeal. The unsuppl...

  14. Assessment of taurine bioavailability in pelleted and extruded diets with red drum Sciaenops ocellatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Taurine has been reported to be efficacious in supporting growth of carnivorous fish species, particularly when supplemented to diets primarily containing plant feedstuffs. Although taurine may become unavailable to some extent by heat and moisture, and is susceptible to the Maillard reaction with r...

  15. Taurine depresses cardiac contractility and enhances systemic heart glucose utilization in the cuttlefish, Sepia officinalis.

    PubMed

    MacCormack, Tyson J; Callaghan, N I; Sykes, A V; Driedzic, W R

    2016-02-01

    Taurine is the most abundant amino acid in the blood of the cuttlefish, Sepia officinalis, where levels can exceed 200 mmol L(-1). In mammals, intracellular taurine modulates cardiac Ca(2+) handling and carbohydrate metabolism at much lower concentrations but it is not clear if it exerts similar actions in cephalopods. Blood Ca(2+) levels are high in cephalopods and we hypothesized that taurine would depress cardiac Ca(2+) flux and modulate contractility in systemic and branchial hearts of cuttlefish. Heart performance was assessed with an in situ perfused systemic heart preparation and contractility was evaluated using isometrically contracting systemic and branchial heart muscle rings. Stroke volume, cardiac output, and Ca(2+) sensitivity were significantly lower in systemic hearts perfused with supplemental taurine (100 mmol L(-1)) than in controls. In muscle ring preparations, taurine impaired relaxation at high contraction frequencies, an effect abolished by supra-physiological Ca(2+) levels. Taurine did not affect oxygen consumption in non-contracting systemic heart muscle, but extracellular glucose utilization was twice that of control preparations. Collectively, our results suggest that extracellular taurine depresses cardiac Ca(2+) flux and potentiates glucose utilization in cuttlefish. Variations in taurine levels may represent an important mechanism for regulating cardiovascular function and metabolism in cephalopods. PMID:26644087

  16. Specific role of taurine in the 8-brominated-2'-deoxyguanosine formation.

    PubMed

    Asahi, Takashi; Nakamura, Yoshimasa; Kato, Yoji; Osawa, Toshihiko

    2015-11-15

    At the sites of inflammation, hypohalous acids, such as hypochlorous acid and hypobromous acid (HOBr), are produced by myeloperoxidase. These hypohalous acids rapidly react with the primary amino groups to produce haloamines, which are relatively stable and can diffuse long distances and cross the plasma membrane. In this study, we examined the effects of taurine, the most abundant free amino acid in the leukocyte cytosol, on the hypohalous acid-dependent formation of 8-chloro-2'-deoxyguanosine (8-CldG) and 8-bromo-2'-deoxyguanosine (8-BrdG). The reaction of taurine with HOBr yielded taurine bromamine, which is the most stable among other bromamines of amino acids. Taurine also enhanced the bromination of only dG among the four 2'-deoxynucleosides, whereas it inhibited the 8-CldG formation. The specificity of taurine for the enhanced formation of halogenated dG is completely different from that of nicotine, an enhancer of chlorination. The amount of dibrominated taurine (taurine dibromamine) closely correlated with the formation of 8-BrdG, suggesting that taurine dibromamine might be a plausible mediator for the dG bromination in vivo. PMID:26456401

  17. Plasma taurine levels are not affected by vigabatrin in pediatric patients.

    PubMed

    Spelbrink, Emily M; Mabud, Tarub S; Reimer, Richard; Porter, Brenda E

    2016-08-01

    Vigabatrin is a highly effective antiseizure medication, but its use is limited due to concerns about retinal toxicity. One proposed mechanism for this toxicity is vigabatrin-mediated reduction of taurine. Herein we assess plasma taurine levels in a retrospective cohort of children with epilepsy, including a subset receiving vigabatrin. All children who underwent a plasma amino acid analysis as part of their clinical evaluation between 2006 and 2015 at Stanford Children's Health were included in the analysis. There were no significant differences in plasma taurine levels between children taking vigabatrin (n = 16), children taking other anti-seizure medications, and children not taking any anti-seizure medication (n = 556) (analysis of variance [ANOVA] p = 0.841). There were, however, age-dependent decreases in plasma taurine levels. Multiple linear regression revealed no significant association between vigabatrin use and plasma taurine level (p = 0.87) when controlling for age. These results suggest that children taking vigabatrin maintain normal plasma taurine levels, although they leave unanswered whether taurine supplementation is necessary or sufficient to prevent vigabatrin-associated visual field loss. They also indicate that age should be taken into consideration when evaluating taurine levels in young children. PMID:27344989

  18. Taurine supplementation in spontaneously hypertensive rats: Advantages and limitations for human applications

    PubMed Central

    Suwanich, Atchariya; Wyss, J Michael; Roysommuti, Sanya

    2013-01-01

    Taurine (2-aminoethanesulfonic acid) is a β-amino acid found in many tissues particularly brain, myocardium, and kidney. It plays several physiological roles including cardiac contraction, antioxidation, and blunting of hypertension. Though several lines of evidence indicate that dietary taurine can reduce hypertension in humans and in animal models, evidence that taurine supplementation reduces hypertension in humans has not been conclusive. One reason for the inconclusive nature of past studies may be that taurine having both positive and negative effects on cardiovascular system depending on when it is assessed, some effects may occur early, while others only appear later. Further, other consideration may play a role, e.g., taurine supplementation improves hypertension in spontaneously hypertensive rats on a low salt diet but fails to attenuate hypertension on a high salt diet. In humans, some epidemiologic studies indicate that people with high taurine and low salt diets display lower arterial pressure than those with low taurine and high salt diets. Differences in techniques for measuring arterial pressure, duration of treatment, and animal models likely affect the response in different studies. This review considers both the positive and negative effects of taurine on blood pressure in animal models and their applications for human interventions. PMID:24340138

  19. Protective role of taurine in developing offspring affected by maternal alcohol consumption

    PubMed Central

    Ananchaipatana-Auitragoon, Pilant; Ananchaipatana-Auitragoon, Yutthana; Siripornpanich, Vorasith; Kotchabhakdi, Naiphinich

    2015-01-01

    Maternal alcohol consumption is known to affect offspring growth and development, including growth deficits, physical anomalies, impaired brain functions and behavioral disturbances. Taurine, a sulfur-containing amino acid, is essential during development, and continually found to be protective against neurotoxicity and various tissue damages including those from alcohol exposure. However, it is still unknown whether taurine can exert its protection during development of central nervous system and whether it can reverse alcohol damages on developed brain later in life. This study aims to investigate protective roles of taurine against maternal alcohol consumption on growth and development of offspring. The experimental protocol was conducted using ICR-outbred pregnant mice given 10 % alcohol, with or without maternal taurine supplementation during gestation and lactation. Pregnancy outcomes, offspring mortality and successive bodyweight until adult were monitored. Adult offspring is supplemented taurine to verify its ability to reverse damages on learning and memory through a water maze task performance. Our results demonstrate that offspring of maternal alcohol exposure, together with maternal taurine supplementation show conserved learning and memory, while that of offspring treated taurine later in life are disturbed. Taurine provides neuroprotective effects and preserves learning and memory processes when given together with maternal alcohol consumption, but not shown such effects when given exclusively in offspring. PMID:26648819

  20. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    SciTech Connect

    Huang, J.-S. Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

    2008-12-01

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27{sup Kip1}, collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells.

  1. Vasopressin-induced taurine efflux from rat pituicytes: a potential negative feedback for hormone secretion.

    PubMed

    Rosso, Lia; Peteri-Brunbäck, Brigitta; Poujeol, Philippe; Hussy, Nicolas; Mienville, Jean-Marc

    2004-02-01

    Previous work on the whole neurohypophysis has shown that hypotonic conditions increase release of taurine from neurohypophysial astrocytes (pituicytes). The present work confirms that taurine is present in cultured pituicytes, and that its specific release increases in response to a hypotonic shock. We next show that vasopressin (VP) and oxytocin (OT) also specifically release taurine from pituicytes. With an EC(50) of approximately 2 nm, VP is much more potent than OT, and the effects of both hormones are blocked by SR 49059, a V(1a) receptor antagonist. This pharmacological profile matches the one for VP- and OT-evoked calcium signals in pituicytes, consistent with the fact that VP-induced taurine efflux is blocked by BAPTA-AM. However, BAPTA-AM also blocks the taurine efflux induced by a 270 mosmol l(-1) challenge, which per se does not evoke any calcium signal, suggesting a permissive role for calcium in this case. Nevertheless, the fact that structurally unrelated calcium-mobilizing agents and ionomycin are able to induce taurine efflux suggests that calcium may also play a signalling role in this event. It is widely accepted that in hypotonic conditions taurine exits cells through anionic channels. Antagonism by the chloride channel inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) suggests the same pathway for VP-induced taurine efflux, which is also blocked in hypertonic conditions (330 mosmol l(-1)). Moreover, it is likely that the osmosensitivity of the taurine channel is up-regulated by calcium. These results, together with our in situ experiments showing stimulation of taurine release by endogenous VP, strengthen the concept of a glial control of neurohormone output. PMID:14617676

  2. Vasopressin-induced taurine efflux from rat pituicytes: a potential negative feedback for hormone secretion

    PubMed Central

    Rosso, Lia; Peteri-Brunbäck, Brigitta; Poujeol, Philippe; Hussy, Nicolas; Mienville, Jean-Marc

    2004-01-01

    Previous work on the whole neurohypophysis has shown that hypotonic conditions increase release of taurine from neurohypophysial astrocytes (pituicytes). The present work confirms that taurine is present in cultured pituicytes, and that its specific release increases in response to a hypotonic shock. We next show that vasopressin (VP) and oxytocin (OT) also specifically release taurine from pituicytes. With an EC50 of ∼2 nm, VP is much more potent than OT, and the effects of both hormones are blocked by SR 49059, a V1a receptor antagonist. This pharmacological profile matches the one for VP- and OT-evoked calcium signals in pituicytes, consistent with the fact that VP-induced taurine efflux is blocked by BAPTA-AM. However, BAPTA-AM also blocks the taurine efflux induced by a 270 mosmol l−1 challenge, which per se does not evoke any calcium signal, suggesting a permissive role for calcium in this case. Nevertheless, the fact that structurally unrelated calcium-mobilizing agents and ionomycin are able to induce taurine efflux suggests that calcium may also play a signalling role in this event. It is widely accepted that in hypotonic conditions taurine exits cells through anionic channels. Antagonism by the chloride channel inhibitors 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) suggests the same pathway for VP-induced taurine efflux, which is also blocked in hypertonic conditions (330 mosmol l−1). Moreover, it is likely that the osmosensitivity of the taurine channel is up-regulated by calcium. These results, together with our in situ experiments showing stimulation of taurine release by endogenous VP, strengthen the concept of a glial control of neurohormone output. PMID:14617676

  3. Ultrasound-assisted extraction and purification of taurine from the red algae Porphyra yezoensis.

    PubMed

    Wang, Fen; Guo, Xiao-Yu; Zhang, Dan-Ni; Wu, Yue; Wu, Tao; Chen, Zhi-Gang

    2015-05-01

    The present study reports on the development of a method using ultrasound-assisted extraction (UAE) during the purification of taurine from Porphyra yezoensis. The Box-Behnken design, which is a widely used form of response surface methodology, was used to investigate the effects of parameters on the UAE process. Three independent variables of taurine purification using UAE were studied including: extraction time, temperature, and ultrasonic power. The results showed that the highest taurine yield of 13.0mg/g was obtained with an extraction time of 38.3 min, the use of 300.0 W ultrasonic power, and an extraction temperature of 40.5°C. A comparative study of taurine extraction was also conducted using either ultrasonication or mechanical agitation. The results indicated that the ultrasonic process required 9 times less time at 40°C to obtain taurine with a similar yield as compared to the conventional extraction method. Therefore, UAE can used as an alternative to the conventional extraction method used during the recovery of taurine from P. yezoensis. The UAE method has several advantages, including that it uses lower extraction temperatures and has a shorter extraction time. The taurine present in the extract supernatant was efficiently separated and purified using a combination of 732 cation exchange chromatography and crystallization. The yield of purified taurine using this process was 1.1%. The structure of the purified taurine was confirmed by FTIR, MS, and NMR. Our findings suggest that P. yezoensis can be used as a taurine-rich food or food material. PMID:25542513

  4. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... or past infection, or immunity to hepatitis A Hepatitis B tests: Hepatitis B surface antigen (HBsAg), you have ...

  5. Hepatitis C and HIV

    MedlinePlus

    ... Problems : Hepatitis C Subscribe Translate Text Size Print Hepatitis C What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis B . Hepatitis C and HIV About 25% of people living ...

  6. Hepatitis B and HIV

    MedlinePlus

    ... Problems : Hepatitis B Subscribe Translate Text Size Print Hepatitis B What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis C . Hepatitis B and HIV About 10% of people living ...

  7. EPR studies of gamma-irradiated taurine single crystals

    NASA Astrophysics Data System (ADS)

    Bulut, A.; Karabulut, B.; Tapramaz, R.; Köksal, F.

    2000-04-01

    An EPR study of gamma-irradiated taurine [C 2H 7NO 3S] single crystal was carried out at room temperature. The EPR spectra were recorded in the three at mutually perpendicular planes. There are two magnetically distinct sites in monoclinic lattice. The principle values of g and hyperfine constants for both sites were calculated. The results have indicated the presence of 32ṠO -2 and 33ṠO -2 radicals. The hyperfine values of 33ṠO -2 radical were used to obtain O-S-O bond angle for both sites.

  8. Hepatitis Testing

    MedlinePlus

    ... caused by viruses. They include hepatitis A, hepatitis B, and hepatitis C. To diagnose hepatitis, your health care provider will ask you about your medical history and symptoms, do a physical exam, and order blood tests. There are blood tests for each type of ...

  9. Characterization of the relaxant response to taurine in rat corpus cavernosum.

    PubMed

    Dalaklioglu-Tasatargil, S

    2013-01-01

    The aim of this study was to evaluate the relaxant effect of taurine, one of the most commonly employed dietary supplements, in rat corpus cavernosum (CC), and to further investigate the contribution of possible underlying mechanisms. Strips of CC were suspended in an organ bath system for isometric tension studies. Taurine (10-80 mmol/l) produced a concentration-dependent relaxation response in rat CC. Endothelial removal did not cause a significant inhibition of the relaxation response to taurine. Incubation of endothelium-denuded CC strips with the nonselective potassium channel blocker tetraethylammonium (10 mmol/l), the ATP-sensitive potassium (KATP) channel blocker glibenclamide (10 μmol/l), the inward rectifier potassium (Kir) channel inhibitor barium chloride (30 μmol/l), and the large conductance calcium-activated potassium channel inhibitor iberiotoxin (0.1 μmol/l) significantly inhibited the relaxant responses to taurine. However, taurine-induced relaxation was not inhibited by the voltage-dependent potassium channel inhibitor 4-aminopyridine (1 mmol/l). On the other hand, taurine (20 mmol/l, 30 min) inhibited both intracellular and extracellular calcium-dependent contraction in CC strips. These findings suggest that taurine induced relaxation of CC via an endothelium-independent pathway. The activation of KATP channels, Kir channels and calcium channels is thought to play an important role in endothelium-independent relaxation of CC, but other direct effects on calcium dynamics may also contribute to its relaxant effect. PMID:23615068

  10. Taurine: the appeal of a safe amino acid for skeletal muscle disorders.

    PubMed

    De Luca, Annamaria; Pierno, Sabata; Camerino, Diana Conte

    2015-01-01

    Taurine is a natural amino acid present as free form in many mammalian tissues and in particular in skeletal muscle. Taurine exerts many physiological functions, including membrane stabilization, osmoregulation and cytoprotective effects, antioxidant and anti-inflammatory actions as well as modulation of intracellular calcium concentration and ion channel function. In addition taurine may control muscle metabolism and gene expression, through yet unclear mechanisms. This review summarizes the effects of taurine on specific muscle targets and pathways as well as its therapeutic potential to restore skeletal muscle function and performance in various pathological conditions. Evidences support the link between alteration of intracellular taurine level in skeletal muscle and different pathophysiological conditions, such as disuse-induced muscle atrophy, muscular dystrophy and/or senescence, reinforcing the interest towards its exogenous supplementation. In addition, taurine treatment can be beneficial to reduce sarcolemmal hyper-excitability in myotonia-related syndromes. Although further studies are necessary to fill the gaps between animals and humans, the benefit of the amino acid appears to be due to its multiple actions on cellular functions while toxicity seems relatively low. Human clinical trials using taurine in various pathologies such as diabetes, cardiovascular and neurological disorders have been performed and may represent a guide-line for designing specific studies in patients of neuromuscular diseases. PMID:26208967

  11. Effect of Cordyceps sinensis and taurine either alone or in combination on streptozotocin induced diabetes.

    PubMed

    El Zahraa Z El Ashry, Fatma; Mahmoud, Mona F; El Maraghy, Nabila N; Ahmed, Ahmed F

    2012-03-01

    The present study aimed to investigate the antidiabetic effects of Cordyceps sinensis, taurine and their combination in comparison with glibenclamide both in vivo and in vitro using streptozotocin rat model. The diabetic rats were orally given glibenclamide, C. sinensis, taurine or Cordyceps and taurine combination for 21 days. Their effects were studied both in vivo and in vitro. Oral administration of Cordyceps, taurine and their combination decreased serum glucose, fructosamine, total cholesterol, triglycerides levels, insulin resistance index and pancreatic malondialdehyde content. Cordyceps significantly increased serum insulin, HDL-cholesterol, total antioxidant capacity levels, β cell function percent, and pancreatic reduced glutathione (GSH) content. However, taurine was unable to elevate pancreatic GSH level to a significant level. These natural products and their combinations were more effective than glibenclamide in reducing insulin resistance index and they had stronger antioxidant properties. Cordyceps and taurine significantly enhanced glucose uptake by diaphragms of normal and diabetic rats in absence and presence of insulin. In conclusion, Cordyceps and taurine either alone or in combination have less potent hypoglycemic effects than glibenclamide; however, they have more ability to reduce insulin resistance and stronger antioxidant properties. PMID:22226943

  12. Comparison of mercury sulfides with mercury chloride and methylmercury on hepatic P450, phase-2 and transporter gene expression in mice.

    PubMed

    Xu, S F; Wu, Q; Zhang, B B; Li, H; Xu, Y S; Du, Y Z; Wei, L X; Liu, J

    2016-09-01

    Zuotai (mainly β-HgS) and Zhusha (also called as cinnabar, mainly α-HgS) are used in traditional medicines in combination with herbs or even drugs in the treatment of various disorders, while mercury chloride (HgCl2) and methylmercury (MeHg) do not have known medical values but are highly toxic. This study aimed to compare the effects of mercury sulfides with HgCl2 and MeHg on hepatic drug processing gene expression. Mice were orally administrated with Zuotai (β-HgS, 30mg/kg), α-HgS (HgS, 30mg/kg), HgCl2 (33.6mg/kg), or MeHg (3.1mg/kg) for 7days, and the expression of genes related to phase-1 drug metabolism (P450), phase-2 conjugation, and phase-3 (transporters) genes were examined. The mercurials at the dose and duration used in the study did not have significant effects on the expression of cytochrome P450 1-4 family genes and the corresponding nuclear receptors, except for a slight increase in PPARα and Cyp4a10 by HgCl2. The expressions of UDP-glucuronosyltransferase and sulfotransferase were increased by HgCl2 and MeHg, but not by Zuotai and HgS. HgCl2 decreased the expression of organic anion transporter (Oatp1a1), but increased Oatp1a4. Both HgCl2 and MeHg increased the expression of multidrug resistance-associated protein genes (Mrp1, Mrp2, Mrp3, and Mrp4). Zuotai and HgS had little effects on these transporter genes. In conclusion, Zuotai and HgS are different from HgCl2 and MeHg in hepatic drug processing gene expression; suggesting that chemical forms of mercury not only affect their disposition and toxicity, but also affect their effects on the expression of hepatic drug processing genes. PMID:27473830

  13. Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death

    SciTech Connect

    Cetiner, Mustafa; Sener, Goeksel; Sehirli, A. Ozer; Eksioglu-Demiralp, Emel; Ercan, Feriha; Sirvanci, Serap; Gedik, Nursal; Akpulat, Sertac; Tecimer, Tuelay; Yegen, Berrak C. . E-mail: byegen@marmara.edu.tr

    2005-11-15

    The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed to measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-{alpha} level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the

  14. Sub-optimal taurine status may promote platelet hyperaggregability in vegetarians.

    PubMed

    McCarty, Mark F

    2004-01-01

    Although vegan diets typically have a very favorable effect on a range of vascular risk factors, several independent groups have reported that the platelets of vegetarians are more sensitive to pro-aggregatory agonists than are those of omnivores. In light of clear and convincing evidence that platelet function has an important impact on risk for thromboembolic events, it is important to clarify the basis of platelet hyperaggregability in vegetarians. A dietary deficit of long-chain omega-3 fatty acids is not likely to explain this phenomenon, since most omnivore diets do not include enough of these fats to discernibly influence platelet function. A more plausible possibility is that relatively poor taurine status--a function of the facts that plants are devoid of taurine and the human capacity for taurine synthesis is limited - is responsible. Plasma taurine levels are lower, and urinary taurine excretion is substantially lower, in vegetarians than in omnivores. Platelets are rich in taurine, which functions physiologically to dampen the calcium influx evoked by aggregating agonists--thereby down-regulating platelet aggregation. Supplemental intakes of taurine as low as 400 mg daily have been reported to markedly decrease the sensitivity of platelets to aggregating agonists ex vivo. Although the average daily intake of taurine from omnivore diets may be only about 150 mg, it is credible to speculate that a supplemental intake of this magnitude could normalize the platelet function of vegetarians in the long term; in any case, this thesis is readily testable clinically. Taurine is just one of a number of nutrients found almost solely in animal products--"carninutrients"--which are rational candidates for supplementation in vegans. PMID:15288361

  15. Nordihydroguaiaretic acid depletes ATP and inhibits a swelling-activated, ATP-sensitive taurine channel.

    PubMed

    Ballatori, N; Wang, W

    1997-05-01

    The mechanism by which nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, prevents swelling-activated organic osmolyte efflux was examined in the human hepatoma cell line Hep G2. When swollen in hypotonic medium, Hep G2 cell exhibited a regulatory volume decrease that was associated with the release of intracellular taurine, an amino acid found at a concentrations of 22.0 +/- 2.5 nmol/mg protein (approximately 5 mM) in these cells. Rate coefficients for swelling-activated [3H]taurine uptake and efflux were unaffected when extracellular taurine was increased from 0.1 to 25 mM, indicating that taurine is released via a channel. Taurine efflux was rapidly activated after cell swelling and immediately inactivated when cells were returned to normal size by restoration of isotonicity. Swelling-activated taurine efflux was not altered by replacement of extracellular Na+ with choline+ or K+ but was inhibited when cellular ATP levels were decreased with a variety of chemical agents, consistent with an ATP-regulated channel previously described in other cell types. NDGA inhibited swelling-activated [3H]taurine efflux in Hep G2 cells at concentrations of 50-150 microM; however, these same concentrations of NDGA also lowered cell ATP levels. Likewise, ketoconazole, an inhibitor of cytochrome P-450 monoxygenases, inhibited [3H]taurine efflux only at concentrations at which cell ATP levels were also lowered. In contrast, other inhibitors of cyclooxygenase (indomethacin, 100 microM) or of lipoxygenases (caffeic acid, 100 microM), as well as arachidonic acid itself (100 microM), had no effect on either taurine efflux or cell ATP. The present findings characterize a swelling-activated, ATP-sensitive osmolyte channel in Hep G2 cells and demonstrate that inactivation of the channel by NDGA is related to the ability of this drug to deplete cellular ATP. PMID:9176131

  16. Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism

    SciTech Connect

    Shao, Xue; Hu, Zhengtao; Hu, Chunyan; Bu, Qian; Yan, Guangyan; Deng, Pengchi; Lv, Lei; Wu, Dan; Deng, Yi; Zhao, Jinxuan; Zhu, Ruiming; Li, Yan; Li, Hongyu; Xu, Youzhi; Yang, Hanshuo; Zhao, Yinglan; Cen, Xiaobo

    2012-05-01

    Investigations have characterized addictive drug-induced developmental cardiovascular malformation in human, non-human primate and rodent. However, the underlying mechanism of malformation caused by drugs during pregnancy is still largely unknown, and preventive and therapeutic measures have been lacking. Using {sup 1}H NMR spectroscopy, we profiled the metabolites from human embryo endothelial cells exposed to methamphetamine (METH) and quantified a total of 226 peaks. We identified 11 metabolites modified robustly and found that taurine markedly increased. We then validated the hypothesis that this dramatic increase in taurine could attribute to its effect in inhibiting METH-induced developmental angiogenesis defect. Taurine supplement showed a more significant potential than other metabolites in protecting against METH-induced injury in endothelial cells. Taurine strongly attenuated METH-induced inhibition of proliferation and migration in endothelial cells. Furthermore, death rate and vessel abnormality of zebrafish embryos treated with METH were greatly reversed by taurine. In addition, taurine supplement caused a rapid decrease in reactive oxygen species generation and strongly attenuated the excitable arise of antioxidase activities in the beginning of METH exposure prophase. Dysregulations of NF-κB, p-ERK as well as Bax, which reflect apoptosis, cell cycle arrest and oxidative stress in vascular endothelium, were blocked by taurine. Our results provide the first evidence that taurine prevents METH-caused developmental angiogenesis defect through antioxidant mechanism. Taurine could serve as a potential therapeutic or preventive intervention of developmental vascular malformation for the pregnant women with drug use. Highlights: ► Metabonomics findings. ► Abnormal development. ► Dysregulations of key proteins.

  17. Effect of taurine and potential interactions with caffeine on cardiovascular function.

    PubMed

    Schaffer, Stephen W; Shimada, Kayoko; Jong, Chian Ju; Ito, Takashi; Azuma, Junichi; Takahashi, Kyoko

    2014-05-01

    The major impetus behind the rise in energy drink popularity among adults is their ability to heighten mental alertness, improve physical performance and supply energy. However, accompanying the exponential growth in energy drink usage have been recent case reports and analyses from the National Poison Data System, raising questions regarding the safety of energy drinks. Most of the safety concerns have centered on the effect of energy drinks on cardiovascular and central nervous system function. Although the effects of caffeine excess have been widely studied, little information is available on potential interactions between the other active ingredients of energy drinks and caffeine. One of the active ingredients often mentioned as a candidate for interactions with caffeine is the beta-amino acid, taurine. Although taurine is considered a conditionally essential nutrient for humans and is thought to play a key role in several human diseases, clinical studies evaluating the effects of taurine are limited. However, based on this review regarding possible interactions between caffeine and taurine, we conclude that taurine should neutralize several untoward effects of caffeine excess. In agreement with this conclusion, the European Union's Scientific Committee on Food published a report in March 2003 summarizing its investigation into potential interactions of the ingredients in energy drinks. At the cardiovascular level, they concluded that "if there are any interactions between caffeine and taurine, taurine might reduce the cardiovascular effects of caffeine." Although these interactions remain to be further examined in humans, the physiological functions of taurine appear to be inconsistent with the adverse cardiovascular symptoms associated with excessive consumption of caffeine-taurine containing beverages. PMID:24615238

  18. Risk Factors for Development of Cholestatic Drug-Induced Liver Injury: Inhibition of Hepatic Basolateral Bile Acid Transporters Multidrug Resistance-Associated Proteins 3 and 4

    PubMed Central

    Köck, Kathleen; Ferslew, Brian C.; Netterberg, Ida; Yang, Kyunghee; Urban, Thomas J.; Swaan, Peter W.; Stewart, Paul W.

    2014-01-01

    Impaired hepatic bile acid export may contribute to development of cholestatic drug-induced liver injury (DILI). The multidrug resistance-associated proteins (MRP) 3 and 4 are postulated to be compensatory hepatic basolateral bile acid efflux transporters when biliary excretion by the bile salt export pump (BSEP) is impaired. BSEP inhibition is a risk factor for cholestatic DILI. This study aimed to characterize the relationship between MRP3, MRP4, and BSEP inhibition and cholestatic potential of drugs. The inhibitory effect of 88 drugs (100 μM) on MRP3- and MRP4-mediated substrate transport was measured in membrane vesicles. Drugs selected for investigation included 50 BSEP non-inhibitors (24 non-cholestatic; 26 cholestatic) and 38 BSEP inhibitors (16 non-cholestatic; 22 cholestatic). MRP4 inhibition was associated with an increased risk of cholestatic potential among BSEP non-inhibitors. In this group, for each 1% increase in MRP4 inhibition, the odds of the drug being cholestatic increased by 3.1%. Using an inhibition cutoff of 21%, which predicted a 50% chance of cholestasis, 62% of cholestatic drugs inhibited MRP4 (P < 0.05); in contrast, only 17% of non-cholestatic drugs were MRP4 inhibitors. Among BSEP inhibitors, MRP4 inhibition did not provide additional predictive value of cholestatic potential; almost all BSEP inhibitors were also MRP4 inhibitors. Inclusion of pharmacokinetic predictor variables (e.g., maximal unbound concentration in plasma) in addition to percent MRP4 inhibition in logistic regression models did not improve cholestasis prediction. Association of cholestasis with percent MRP3 inhibition was not statistically significant, regardless of BSEP-inhibition status. Inhibition of MRP4, in addition to BSEP, may be a risk factor for the development of cholestatic DILI. PMID:24154606

  19. Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study.

    PubMed

    Sun, Qianqian; Wang, Bin; Li, Yingsha; Sun, Fang; Li, Peng; Xia, Weijie; Zhou, Xunmei; Li, Qiang; Wang, Xiaojing; Chen, Jing; Zeng, Xiangru; Zhao, Zhigang; He, Hongbo; Liu, Daoyan; Zhu, Zhiming

    2016-03-01

    Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to lower blood pressure (BP) in hypertensive animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human hypertension or prehypertension, a key stage in the development of hypertension. In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on BP and vascular function in prehypertension. We randomly assigned 120 eligible prehypertensive individuals to receive either taurine supplementation (1.6 g per day) or a placebo for 12 weeks. Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H2S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H2S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment upregulated the expression of hydrogen sulfide-synthesizing enzymes and reduced agonist-induced vascular reactivity through the inhibition of transient receptor potential channel subtype 3-mediated calcium influx in human and mouse mesenteric arteries. In conclusion, the antihypertensive effect of chronic taurine supplementation shows promise in the treatment of prehypertension through improvement of vascular function. PMID:26781281

  20. Hepatitis B and Hepatitis C in Pregnancy

    MedlinePlus

    ... infected with the hepatitis B virus, can I breastfeed? • If I am infected with the hepatitis B ... infected with the hepatitis C virus, can I breastfeed? • Glossary What are hepatitis B and hepatitis C ...

  1. Vibrational spectra and molecular conformation of taurine and its related compounds

    NASA Astrophysics Data System (ADS)

    Ohno, Keiichi; Mandai, Yoshitaka; Matsuura, Hiroatsu

    1992-04-01

    IR and Raman spectra have been measured for taurine (2-aminoethanesulfonic acid) and its sodium salt in the solid state and Raman spectra for aqueous solutions of taurine with different pH values. Normal coordinate treatment has been carried out. The analysis of the spectra has indicated that, in the solid state, the molecule of taurine takes the gauche form while that of the sodium salt takes the trans form, and that the trans and gauche forms coexist in both acidic and basic aqueous solutions. The CS stretching bands for the gauche and trans forms were observed at 742 cm -1 and 803 cm -1 respectively. These bands were applied to a conformational analysis of other compounds containing a taurine skeleton; sodium taurocholate takes the gauche conformation about the bond axis NCCS.

  2. Concentrative nucleoside transporter (rCNT1) is targeted to the apical membrane through the hepatic transcytotic pathway.

    PubMed

    Duflot, Sylvie; Calvo, Maria; Casado, F Javier; Enrich, Carlos; Pastor-Anglada, Marçal

    2002-11-15

    The Na+-dependent nucleoside transporter CNT1 has been identified in a caveolin-enriched plasma membrane fraction (CEF), in transcytotic endosomes, and in canalicular membranes isolated from quiescent rat liver in which the transporter appears to be biologically active. CNT1 was also detected, albeit in small amounts, in the early/sorting endosomes. Plasma membrane preparations enriched in basolateral markers showed Na+-dependent nucleoside transport activity that is mostly, if not exclusively, accounted for by CNT2, a transporter protein which was not detected in CEF nor in the endosomal fractions. These data are consistent with different localization and trafficking pathways of the two isoforms in hepatocytes. CNT1 is the first transporter which is reported to follow the transcytotic pathway to be inserted on the apical side of liver parenchymal cells. PMID:12441131

  3. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... There are different tests for hepatitis A and B. A positive test is ... may mean: You currently have a hepatitis infection. This may ...

  4. Hepatitis C and Incarceration

    MedlinePlus

    HEPATITIS C & INCARCERATION What is hepatitis? “Hepatitis” means inflammation or swelling of the liver. The liver is an important ... viral hepatitis: Hepatitis A, Hepatitis B, and Hepatitis C. They are all different from each other and ...

  5. Hepatitis C: Treatment

    MedlinePlus

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  6. Taurine attenuates D-[3H]aspartate release evoked by depolarization in ischemic corticostriatal slices.

    PubMed

    Molchanova, Svetlana M; Oja, Simo S; Saransaari, Pirjo

    2006-07-12

    Taurine is thought to be protective in ischemia due to its neuroinhibitory effects. The present aim was to assess the ability of taurine to attenuate glutamate release evoked by ischemia and to determine which component of this release is affected. The release of preloaded D-[(3)H]aspartate (a non-metabolized analog of glutamate) from superfused murine corticostriatal slices was used as index of glutamate release. Preincubation of corticostriatal slices with 10 mM taurine reduced the D-[(3)H]aspartate release evoked by either chemical ischemia (0.5 mM NaCN in glucose-free medium) or oxygen-glucose deprivation. The taurine uptake inhibitor guanidinoethanesulfonate (5 mM), the glycine receptor antagonist strychnine (0.1 mM) and the GABA(A) receptor antagonist bicuculline (0.1 mM) did not block the taurine effect. To determine which component of ischemia-induced glutamate release is affected by taurine, three pathways of this release were pharmacologically modeled. Unlabeled D-aspartate (0.5 mM) and hypo-osmotic medium (NaCl reduced by 50 mM) evoked D-[(3)H]aspartate release via homoexchange and hypo-osmotic release pathways, respectively. Taurine did not influence these pathways. However, it suppressed the synaptic release of D-[(3)H]aspartate evoked by the voltage-gated sodium channel opener veratridine (0.1 mM). Taurine thus reduces glutamate release under ischemic conditions by affecting the depolarization-evoked component. PMID:16781687

  7. Electrophysiological actions of taurine on spontaneously beating rabbit sino-atrial nodal cells.

    PubMed

    Satoh, H

    1995-01-01

    Effects of taurine on the spontaneous action potentials in rabbit sino-atrial nodal cells were examined at different extracellular Ca2+ concentrations ([Ca]o). Experiments were performed at 36 degrees C. The firing rate of spontaneous activity was 132.5 +/- 12.1 beats/min (n = 18) in normal Tyrode's solution ([Ca]o = 1.8 mM). Increasing [Ca]o level from 0.9 to 10.8 mM significantly changed the maximum rate of depolarization. Other parameters of the action potentials were unaffected. When [Ca]o was 0.9 mM, application of taurine (1 to 20 mM) tended to cause a positive chronotropic effect and hyperpolarized the maximum diastolic potential. In the normal solution (at 1.8 mM [Ca]o), taurine significantly enhanced only the maximum rate of depolarization. In contrast, under high [Ca]o (5.4 and 10.8 mM), taurine at 1 and 5 mM had a negative chronotropic effect, but 20 mM taurine had a positive chronotropic effect. Also, taurine shortened the action potential duration and hyperpolarized the maximum diastolic potential. The maximum rate of depolarization was inhibited. In 10.8 mM [Ca]o solution, irregular spontaneous activity (dysrhythmias) occurred in 4 of 6 preparations, and addition of taurine (1 to 20 mM) abolished it. These results indicate that taurine modulates the action potential configuration in the sino-atrial nodal cells dependent on [Ca]o. PMID:7745842

  8. Hepatic ischemia

    MedlinePlus

    Hepatic ischemia is a condition in which the liver does not get enough blood or oxygen, causing injury to ... pressure from any condition can lead to hepatic ischemia. Such conditions may include: Abnormal heart rhythms Dehydration ...

  9. Hepatic Encephalopathy

    MedlinePlus Videos and Cool Tools

    ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that ... medical care is an important factor in staying as healthy as possible. The American Liver Foundation is ...

  10. Hepatitis D

    MedlinePlus

    ... if the hepatitis B virus is also present. Transmission Hepatitis D can be found in the blood, ... other body fluids of people who are infected. Transmission happens when infected body fluid enters another person’s ...

  11. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  12. Hepatitis C

    MedlinePlus

    ... 2014 Select a Language: Fact Sheet 507 Hepatitis C WHAT IS HEPATITIS C? HOW IS IT DIAGNOSED? ... treatment may be less likely to work. Hep C treatment is less effective for coinfected people. Cure ...

  13. Hepatitis A

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... washed in untreated water Putting into your mouth a finger or object that came into contact with ...

  14. Hepatitis B

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000279.htm Hepatitis B To use the sharing features on this page, please enable JavaScript. Hepatitis B is irritation and swelling (inflammation) of the ...

  15. Effect of taurine on the concentrations of glutamate, GABA, glutamine and alanine in the rat striatum and hippocampus.

    PubMed

    Molchanova, Svetlana M; Oja, Simos S; Saransaari, Pirjo

    2007-01-01

    Taurine, a non-protein amino acid, acts as an osmoregulator and inhibitory neuromodulator in the brain. Here we studied the effects of intraperitoneal injections of taurine on the concentrations of glutamate and GABA, and their precursors, glutamine and alanine, in the rat striatum and hippocampus. Injections of 0.25, 0.5 and 1 g/kg taurine led to a gradual increase in taurine tissue concentrations in both hippocampus and striatum. Glutamate and GABA also increased in the hippocampus, but not in the striatum. Glutamine increased and alanine decreased markedly in both brain structures. The results corroborate the neuromodulatory role of taurine in the brain. Taurine administration results in an imbalance in inhibitory and excitatory neurotransmission in the glutamatergic (hippocampus) and GABAergic (striatum) brain structures, affecting more markedly the neurotransmitter precursors. PMID:18605241

  16. Fish and lifestyle-related disease prevention: experimental and epidemiological evidence for anti-atherogenic potential of taurine.

    PubMed

    Yamori, Yukio; Murakami, Shigeru; Ikeda, Katsumi; Nara, Yasuo

    2004-12-01

    1. Taurine supplementation attenuated the development of hypertension and stroke in stroke-prone spontaneously hypertensive rats (SHRSP). 2. WHO-CARDIAC (Cardiovascular Diseases Alimentary Comparison) study revealed wide differences in 24-h urinary taurine excretion, which were inversely associated with age-adjusted mortality rates of coronary heart diseases (CHD). 3. Hypercholesterolemia as well as arterial fat deposition related to the cause of CHD was attenuated by dietary taurine supplementation in SHRSP on high-fat cholesterol diet. 4. Taurine affected the gene expression of 7alpha-hydroxylase and thus regulated serum cholesterol level through the control of the rate limiting step of cholesterol excretion into bile acids. 5. Taurine attenuated atherogenesis due to the control of oxidative stress through the inhibition of the production of oxidative LDL and to its scavenger effect on hypochlorous acid (HOCl) from leucocytes and macrophages. 6. Taurine may act as an immunomodulator of cytokine production, which is involved in atherogenesis. PMID:15649278

  17. Somatostatin inhibits the effect of secretin on bile flow and on hepatic bilirubin transport in the rat.

    PubMed Central

    Ricci, G L; Fevery, J

    1989-01-01

    Increasing amounts of porcine secretion (0.05 to 2.00 clinical units/h/100 g body wt) given to rats during a continuous infusion of bilirubin, increased bile flow and the apparent maximal biliary excretion of bilirubin ('Tm'). This increment was caused by an enhanced biliary output of bilirubin monoconjugates. The effect was dose dependent but maximal at a secretin infusion of 0.80 CU. Somatostatin 0.2 and 0.8 microgram/h/100 g body wt caused a dose related inhibition of the hepatic effects of secretin both on bile flow and on biliary output of bilirubin conjugates. As secretin elicits the release of somatostatin, a feed-back system could be envisaged whereby the somatostatin released stops the effects of secretin. PMID:2572517

  18. Identification of a Vibrio cholerae chemoreceptor that senses taurine and amino acids as attractants.

    PubMed

    Nishiyama, So-ichiro; Takahashi, Yohei; Yamamoto, Kentaro; Suzuki, Daisuke; Itoh, Yasuaki; Sumita, Kazumasa; Uchida, Yumiko; Homma, Michio; Imada, Katsumi; Kawagishi, Ikuro

    2016-01-01

    Vibrio cholerae, the etiological agent of cholera, was found to be attracted by taurine (2-aminoethanesulfonic acid), a major constituent of human bile. Mlp37, the closest homolog of the previously identified amino acid chemoreceptor Mlp24, was found to mediate taxis to taurine as well as L-serine, L-alanine, L-arginine, and other amino acids. Methylation of Mlp37 was enhanced upon the addition of taurine and amino acids. Isothermal titration calorimetry demonstrated that a purified periplasmic fragment of Mlp37 binds directly to taurine, L-serine, L-alanine and L-arginine. Crystal structures of the periplamic domain of Mlp37 revealed that L-serine and taurine bind to the membrane-distal PAS domain in essentially in the same way. The structural information was supported by characterising the in vivo properties of alanine-substituted mutant forms of Mlp37. The fact that the ligand-binding domain of the L-serine complex had a small opening, which would accommodate a larger R group, accounts for the broad ligand specificity of Mlp37 and allowed us to visualise ligand binding to Mlp37 with fluorescently labelled L-serine. Taken together, we conclude that Mlp37 serves as the major chemoreceptor for taurine and various amino acids. PMID:26878914

  19. Taurine and Epidermal Growth Factor Belong to the Signature of First-Episode Psychosis

    PubMed Central

    Koido, Kati; Innos, Jürgen; Haring, Liina; Zilmer, Mihkel; Ottas, Aigar; Vasar, Eero

    2016-01-01

    This study evaluated the levels of two amino acid derivatives taurine and spermine in first-episode psychosis (FEP) patients and their response to antipsychotic treatment. The levels of taurine and spermine were significantly up-regulated in antipsychotic-naïve FEP patients compared to control subjects (CS). Treatment of FEP patients with antipsychotic drugs significantly reduced the positive symptoms of schizophrenia. This positive effect was accompanied by a significant reduction of taurine and spermine to the levels measured in CS. General linear model was used to establish associations of taurine and spermine with the levels of cytokines and growth factors, measured in our previous experiments using the same study sample. There was a strong association between taurine and epidermal growth factor (EGF). Both biomarkers significantly correlated with the disease symptoms as well as with the effectiveness of antipsychotic treatment. Accordingly one can conclude that taurine and EGF belong to the signature of FEP. Most probably they reflect altered oxidative stress and corrupted function of N-methyl-D-aspartate (NMDA) receptors in FEP. PMID:27471446

  20. Comparison of taurine, GABA, Glu, and Asp as scavengers of malondialdehyde in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Deng, Yan; Wang, Wei; Yu, Pingfeng; Xi, Zhijiang; Xu, Lijian; Li, Xiaolong; He, Nongyue

    2013-04-01

    The purpose of this study is to determine if amino acid neurotransmitters such as gamma-aminobutyric acid (GABA), taurine, glutamate (Glu), and aspartate (Asp) can scavenge activated carbonyl toxicants. In vitro, direct reaction between malondialdehyde (MDA) and amino acids was researched using different analytical methods. The results indicated that scavenging activated carbonyl function of taurine and GABA is very strong and that of Glu and Asp is very weak in pathophysiological situations. The results provided perspective into the reaction mechanism of taurine and GABA as targets of activated carbonyl such as MDA in protecting nerve terminals. In vivo, we studied the effect of taurine and GABA as antioxidants by detecting MDA concentration and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. It was shown that MDA concentration was decreased significantly, and the activities of SOD and GSH-Px were increased significantly in the cerebral cortex and hippocampus of acute epileptic state rats, after the administration of taurine and GABA. The results indicated that the peripherally administered taurine and GABA can scavenge free radicals and protect the tissue against activated carbonyl in vivo and in vitro.

  1. Identification of a Vibrio cholerae chemoreceptor that senses taurine and amino acids as attractants

    PubMed Central

    Nishiyama, So-ichiro; Takahashi, Yohei; Yamamoto, Kentaro; Suzuki, Daisuke; Itoh, Yasuaki; Sumita, Kazumasa; Uchida, Yumiko; Homma, Michio; Imada, Katsumi; Kawagishi, Ikuro

    2016-01-01

    Vibrio cholerae, the etiological agent of cholera, was found to be attracted by taurine (2-aminoethanesulfonic acid), a major constituent of human bile. Mlp37, the closest homolog of the previously identified amino acid chemoreceptor Mlp24, was found to mediate taxis to taurine as well as L-serine, L-alanine, L-arginine, and other amino acids. Methylation of Mlp37 was enhanced upon the addition of taurine and amino acids. Isothermal titration calorimetry demonstrated that a purified periplasmic fragment of Mlp37 binds directly to taurine, L-serine, L-alanine and L-arginine. Crystal structures of the periplamic domain of Mlp37 revealed that L-serine and taurine bind to the membrane-distal PAS domain in essentially in the same way. The structural information was supported by characterising the in vivo properties of alanine-substituted mutant forms of Mlp37. The fact that the ligand-binding domain of the L-serine complex had a small opening, which would accommodate a larger R group, accounts for the broad ligand specificity of Mlp37 and allowed us to visualise ligand binding to Mlp37 with fluorescently labelled L-serine. Taken together, we conclude that Mlp37 serves as the major chemoreceptor for taurine and various amino acids. PMID:26878914

  2. Taurine suppresses the spread of cell death in electrically coupled RPE cells

    PubMed Central

    Udawatte, Chandani; Qian, Haohua; Mangini, Nancy J.; Kennedy, Brian G.

    2008-01-01

    Purpose To determine whether taurine exerts a protective effect on retinal pigment epithelium (RPE) cells exposed to a cytotoxic agent, cytochrome C (cyC), shown previously to induce apoptosis and produce cell death in electrically coupled neighboring cells. Methods Monolayer cultures of confluent human RPE (ARPE-19) cells, which express gap-junctional proteins, were incubated in culture medium with or without taurine. After scrape loading cyC into the cells, we assayed these cells for caspase 3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining to determine the spread of apoptosis. Results We found that cyC, too large a molecule to traverse gap junctional channels, produced apoptosis in cells injured by the scrape as well as those distant from the site of the scrape, presumably by the intercellular transmission of a toxic agent through the gap junctions that couple these cells. Incubation in taurine, or the gap-junction blocker, octanol, before application of cyC, reduced significantly the fraction of cells undergoing apoptosis. Voltage clamp recordings from electrically coupled Xenopus oocytes transfected with Cx43 showed that junctional communication was unaffected by taurine. Conclusions Our results indicate that taurine can serve to suppress cell death in RPE cells independent of any effect on gap junctions. We have considered various avenues by which taurine can exert its protective effect, but the precise mechanism involved under these experimental conditions has yet to be identified. PMID:18958305

  3. Physiological concentrations of zinc reduce taurine-activated GlyR responses to drugs of abuse.

    PubMed

    Kirson, Dean; Cornelison, Garrett L; Philpo, Ashley E; Todorovic, Jelena; Mihic, S John

    2013-12-01

    Taurine is an endogenous ligand acting on glycine receptors in many brain regions, including the hippocampus, prefrontal cortex, and nucleus accumbens (nAcc). These areas also contain low concentrations of zinc, which is known to potentiate glycine receptor responses. Despite an increasing awareness of the role of the glycine receptor in the rewarding properties of drugs of abuse, the possible interactions of these compounds with zinc has not been thoroughly addressed. Two-electrode voltage-clamp electrophysiological experiments were performed on α1, α2 α1β and α2β glycine receptors expressed in Xenopus laevis oocytes. The effects of zinc alone, and zinc in combination with other positive modulators on the glycine receptor, were investigated when activated by the full agonist glycine versus the partial agonist taurine. Low concentrations of zinc enhanced responses of maximally-effective concentrations of taurine but not glycine. Likewise, chelation of zinc from buffers decreased responses of taurine- but not glycine-mediated currents. Potentiating concentrations of zinc decreased ethanol, isoflurane, and toluene enhancement of maximal taurine currents with no effects on maximal glycine currents. Our findings suggest that the concurrence of high concentrations of taurine and low concentrations of zinc attenuate the effects of additional modulators on the glycine receptor, and that these conditions are more representative of in vivo functioning than effects seen when these modulators are applied in isolation. PMID:23973295

  4. Physiological concentrations of zinc reduce taurine-activated GlyR responses to drugs of abuse

    PubMed Central

    Kirson, Dean; Cornelison, Garrett L.; Philpo, Ashley E.; Todorovic, Jelena; Mihic, S. John

    2013-01-01

    Taurine is an endogenous ligand acting on glycine receptors in many brain regions, including the hippocampus, prefrontal cortex, and nucleus accumbens (nAcc). These areas also contain low concentrations of zinc, which is known to potentiate glycine receptor responses. Despite an increasing awareness of the role of the glycine receptor in the rewarding properties of drugs of abuse, the possible interactions of these compounds with zinc has not been thoroughly addressed. Two-electrode voltage-clamp electrophysiological experiments were performed on α1, α2 α1β and a2β glycine receptors expressed in Xenopus laevis oocytes. The effects of zinc alone, and zinc in combination with other positive modulators on the glycine receptor, were investigated when activated by the full agonist glycine versus the partial agonist taurine. Low concentrations of zinc enhanced responses of maximally-effective concentrations of taurine but not glycine. Likewise, chelation of zinc from buffers decreased responses of taurine- but not glycine-mediated currents. Potentiating concentrations of zinc decreased ethanol, isoflurane, and toluene enhancement of maximal taurine currents with no effects on maximal glycine currents. Our findings suggest that the concurrence of high concentrations of taurine and low concentrations of zinc attenuate the effects of additional modulators on the glycine receptor, and that these conditions are more representative of in vivo functioning than effects seen when these modulators are applied in isolation. PMID:23973295

  5. Quantification of taurine in energy drinks using ¹H NMR.

    PubMed

    Hohmann, Monika; Felbinger, Christine; Christoph, Norbert; Wachter, Helmut; Wiest, Johannes; Holzgrabe, Ulrike

    2014-05-01

    The consumption of so called energy drinks is increasing, especially among adolescents. These beverages commonly contain considerable amounts of the amino sulfonic acid taurine, which is related to a magnitude of various physiological effects. The customary method to control the legal limit of taurine in energy drinks is LC-UV/vis with postcolumn derivatization using ninhydrin. In this paper we describe the quantification of taurine in energy drinks by (1)H NMR as an alternative to existing methods of quantification. Variation of pH values revealed the separation of a distinct taurine signal in (1)H NMR spectra, which was applied for integration and quantification. Quantification was performed using external calibration (R(2)>0.9999; linearity verified by Mandel's fitting test with a 95% confidence level) and PULCON. Taurine concentrations in 20 different energy drinks were analyzed by both using (1)H NMR and LC-UV/vis. The deviation between (1)H NMR and LC-UV/vis results was always below the expanded measurement uncertainty of 12.2% for the LC-UV/vis method (95% confidence level) and at worst 10.4%. Due to the high accordance to LC-UV/vis data and adequate recovery rates (ranging between 97.1% and 108.2%), (1)H NMR measurement presents a suitable method to quantify taurine in energy drinks. PMID:24094700

  6. Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

    PubMed

    Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2016-06-01

    Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. PMID:27345710

  7. Taurine Attenuates Dimethylbenz[a]anthracene-induced Breast Tumorigenesis in Rats: A Plasma Metabolomic Study.

    PubMed

    He, Y U; Li, Qingdi Quentin; Guo, Song Chao

    2016-02-01

    Breast cancer is the most common malignancy and the leading cause of cancer-related mortality in women worldwide. Taurine, the most abundant free amino acid, plays a role in several biological processes in humans and has been shown to have activity against breast cancer and other tumors. To investigate the role and mechanism of taurine action in breast cancer, we used dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in rats as a model of breast cancer. The administration of taurine significantly reduced the DMBA-induced breast cancer rate from 80% to 40% in rats (p<0.05). Metabolomic studies using time-of-flight gas chromatography-mass spectrometry identified 23 differential metabolites in the plasma of taurine-administered rats. Bioinformatic analysis further revealed that these metabolites are involved in multiple metabolic pathways, including energy, glucose, amino acid, and nucleic acid metabolism, suggesting that the antitumor activity of taurine in rats is mediated through altered metabolism of breast cancer cells. We propose that these differential metabolites may be potential biomarkers for monitoring cancer therapy and prognosis in the clinic. This study provides a scientific basis for further investigations of the antitumor mechanism of taurine and the development of novel therapeutic strategies to treat breast cancer. PMID:26851007

  8. Pregnancy failure in cats associated with long-term dietary taurine insufficiency.

    PubMed

    Dieter, J A; Stewart, D R; Haggarty, M A; Stabenfeldt, G H; Lasley, B L

    1993-01-01

    The effect of long-term dietary taurine insufficiency on reproductive function was studied in adult female domestic cats (n = 11). Cats were time-mated during taurine-deficient (6 months) and refed (6 months) states, and the outcome of ovulatory cycles and breeding was analysed. Serum progesterone and relaxin concentrations were evaluated in order to characterize pregnancies, including those resulting in resorption of fetuses, and pseudopregnancies. Increased resorption of fetuses, reduced litter size, and increased incidence of stillborn kittens was observed in queens while on taurine-deficient diets, as well as after refeeding of a taurine-enriched diet. Overall, 30% of the ovulatory cycles resulted in the delivery of kittens, with mean live and stillborn litter sizes of 2.2 +/- 0.4 and 0.8 +/- 0.4 kittens (mean +/- SEM), respectively. The remaining ovulatory cycles resulted either in pregnancies in which fetuses were resorbed (38%), or in pseudopregnancies (32%). Ovulatory cycles resulting in resorbed fetuses were characterized by the appearance of relaxin on day 20 of gestation, but with a subsequent decrease to non-pregnant concentrations by day 25 of gestation. These results suggest that reproductive failure in domestic cats exposed to long-term nutritional taurine deficiency is associated with a postovulatory defect manifest within the first 10 days after implantation, and that this defect is not reversible upon refeeding of a taurine-enriched diet for 6 months. PMID:8229962

  9. Hepatitis A

    MedlinePlus

    ... is an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... suggest medicines to help relieve your symptoms. The hepatitis A vaccine can prevent HAV. Good hygiene can also ...

  10. Hepatitis C

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

  11. Hepatitis A

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Español Hepatitis A Page Content On this page: What is ... Nutrition Points to Remember Clinical Trials What is hepatitis A? Hepatitis * A is a virus , or infection, ...

  12. Autoimmune Hepatitis

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Autoimmune Hepatitis Page Content On this page: What is autoimmune ... Points to Remember Clinical Trials What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ...

  13. The anti-TNF-α antibody infliximab inhibits the expression of fat-transporter-protein FAT/CD36 in a selective hepatic-radiation mouse model.

    PubMed

    Martius, Gesa; Cameron, Silke; Rave-Fränk, Margret; Hess, Clemens F; Wolff, Hendrik A; Malik, Ihtzaz A

    2015-01-01

    Previously, we reported a radiation-induced inflammation triggering fat-accumulation through fatty-acid-translocase/cluster of differentiation protein 36 (FAT/CD36) in rat liver. Furthermore, inhibition of radiation-induced FAT/CD36-expression by anti-tumor necrosis factor-α (anti-TNF-α) (infliximab) was shown in vitro. The current study investigates fat-accumulation in a mouse-model of single-dose liver-irradiation (25-Gray) and the effect of anti-TNF-α-therapy on FAT/CD36 gene-expression. Mice livers were selectively irradiated in vivo in presence or absence of infliximab. Serum- and hepatic-triglycerides, mRNA, and protein were analyzed by colorimetric assays, RT-PCR, Immunofluorescence and Western-Blot, respectively. Sudan-staining was used demonstrating fat-accumulation in tissue. In mice livers, early (1-3 h) induction of TNF-α-expression, a pro-inflammatory cytokine, was observed. It was followed by elevated hepatic-triglyceride level (6-12 h), compared to sham-irradiated controls. In contrast, serum-triglyceride level was decreased at these time points. Similar to triglyceride level in mice livers, Sudan staining of liver cryosections showed a quick (6-12 h) increase of fat-droplets after irradiation. Furthermore, expression of fat-transporter-protein FAT/CD36 was increased at protein level caused by radiation or TNF-α. TNF-α-blockage by anti-TNF-α showed an early inhibition of radiation-induced FAT/CD36 expression in mice livers. Immunohistochemistry showed basolateral and cytoplasmic expression of FAT/CD36 in hepatocytes. Moreover, co-localization of FAT/CD36 was detected with α-smooth muscle actin (α-SMA+) cells and F4/80+ macrophages. In summary, hepatic-radiation triggers fat-accumulation in mice livers, involving acute-phase-processes. Accordingly, anti-TNF-α-therapy prevented early radiation-induced expression of FAT/CD36 in vivo. PMID:25739082

  14. The Anti-TNF-α Antibody Infliximab Inhibits the Expression of Fat-Transporter-Protein FAT/CD36 in a Selective Hepatic-Radiation Mouse Model

    PubMed Central

    Martius, Gesa; Cameron, Silke; Rave-Fränk, Margret; Hess, Clemens F.; Wolff, Hendrik A.; Malik, Ihtzaz A.

    2015-01-01

    Previously, we reported a radiation-induced inflammation triggering fat-accumulation through fatty-acid-translocase/cluster of differentiation protein 36 (FAT/CD36) in rat liver. Furthermore, inhibition of radiation-induced FAT/CD36-expression by anti-tumor necrosis factor-α (anti-TNF-α) (infliximab) was shown in vitro. The current study investigates fat-accumulation in a mouse-model of single-dose liver-irradiation (25-Gray) and the effect of anti-TNF-α-therapy on FAT/CD36 gene-expression. Mice livers were selectively irradiated in vivo in presence or absence of infliximab. Serum- and hepatic-triglycerides, mRNA, and protein were analyzed by colorimetric assays, RT-PCR, Immunofluorescence and Western-Blot, respectively. Sudan-staining was used demonstrating fat-accumulation in tissue. In mice livers, early (1–3 h) induction of TNF-α-expression, a pro-inflammatory cytokine, was observed. It was followed by elevated hepatic-triglyceride level (6–12 h), compared to sham-irradiated controls. In contrast, serum-triglyceride level was decreased at these time points. Similar to triglyceride level in mice livers, Sudan staining of liver cryosections showed a quick (6–12 h) increase of fat-droplets after irradiation. Furthermore, expression of fat-transporter-protein FAT/CD36 was increased at protein level caused by radiation or TNF-α. TNF-α-blockage by anti-TNF-α showed an early inhibition of radiation-induced FAT/CD36 expression in mice livers. Immunohistochemistry showed basolateral and cytoplasmic expression of FAT/CD36 in hepatocytes. Moreover, co-localization of FAT/CD36 was detected with α-smooth muscle actin (α-SMA+) cells and F4/80+ macrophages. In summary, hepatic-radiation triggers fat-accumulation in mice livers, involving acute-phase-processes. Accordingly, anti-TNF-α-therapy prevented early radiation-induced expression of FAT/CD36 in vivo. PMID:25739082

  15. Psidium guajava Linn. leaf extract affects hepatic glucose transporter-2 to attenuate early onset of insulin resistance consequent to high fructose intake: An experimental study

    PubMed Central

    Mathur, R.; Dutta, Shagun; Velpandian, T.; Mathur, S.R.

    2015-01-01

    Background: Insulin resistance (IR) is amalgam of pathologies like altered glucos metabolism, dyslipidemia, impaired glucose tolerance, non-alcoholic fatty liver disease, and associated with type-II diabetes and cardiometabolic diseases. One of the reasons leading to its increased and early incidence is understood to be a high intake of processed fructose containing foods and beverages by individuals, especially, during critical developmental years. Objective: To investigate the preventive potential of aqueous extract of Psidium guajava leaves (PG) against metabolic pathologies, vis-à-vis, IR, dyslipidemia, hyperleptinemia and hypertension, due to excess fructose intake initiated during developmental years. Materials and Methods: Post-weaning (4 weeks old) male rats were provided fructose (15%) as drinking solution, ad libitum, for 8 weeks and assessed for food and water/fructose intake, body weight, fasting blood sugar, mean arterial pressure, lipid biochemistry, endocrinal (insulin, leptin), histopathological (fatty liver) and immunohistochemical (hepatic glucose transporter [GLUT2]) parameters. Parallel treatment groups were administered PG in doses of 250 and 500 mg/kg/d, po × 8 weeks and assessed for same parameters. Using extensive liquid chromatography-mass spectrometry protocols, PG was analyzed for the presence of phytoconstituents like Myrecetin, Luteolin, Kaempferol and Guavanoic acid and validated to contain Quercetin up to 9.9%w/w. Results: High fructose intake raised circulating levels of insulin and leptin and hepatic GLUT2 expression to promote IR, dyslipidemia, and hypertension that were favorably re-set with PG. Although PG is known for its beneficial role in diabetes mellitus, for the first time we report its potential in the management of lifelong pathologies arising from high fructose intake initiated during developmental years. PMID:25829790

  16. Effect of vitamin B6 status of the lactating rat on taurine biosynthesis and availability to the pup

    SciTech Connect

    Trumbo, P. )

    1990-02-26

    Cysteinesulfinate decarboxylase (CD), a pyridoxal 5{prime}-phosphate-dependent enzyme, is believed to be rate-limiting for taurine biosynthesis in the rat. Although taurine is synthesized by the pup, it is abundant in milk of the lactating rat. CD activity has been shown to be reduced in vitamin B6-deficient, lactating rats and their pups, without much change in taurine concentration of certain tissues. To further understand the effect of B6 status of lactating rats on taurine biosynthesis and availability to their pups, pregnant dams were fed either a B6-deficient or B6-adequate (20 mg/kg) diet during gestation and 10 days postpartum. After this time period, all dams were gavaged {sup 35}S cysteine and {sup 3}H taurine, milk and tissues of the dams and pups collected, and taurine isolated by ion-exchange chromatography. There was no difference in the {sup 35}S/{sup 3}H ratio in the heart or liver for the adequate and deficient dams. The {sup 35}S/{sup 3}H ratio was slightly but significantly greater in the liver of the B6-adequate pups compared to the B6-deficient pups without a difference in the level of {sup 3}H taurine (pmol/gram protein) in the milk or pup's liver. Results indicate that a B6 deficiency can influence taurine biosynthesis in the pup without impairing secretion of taurine in milk.

  17. Taurine attenuates methamphetamine-induced autophagy and apoptosis in PC12 cells through mTOR signaling pathway.

    PubMed

    Li, Yan; Hu, Zhengtao; Chen, Bo; Bu, Qian; Lu, Wenjie; Deng, Yi; Zhu, Ruiming; Shao, Xue; Hou, Jing; Zhao, Jinxuan; Li, Hongyu; Zhang, Baolai; Huang, Yina; Lv, Lei; Zhao, Yinglan; Cen, Xiaobo

    2012-11-23

    Methamphetamine (METH), a commonly abused psychostimulant, has been shown to induce neuronal damage by causing reactive oxygen species (ROS) formation, apoptosis and autophagy. Taurine (2-aminoethanesulfonic acid) is involved in several physiological actions in the brain, including neuroprotection, osmoregulation and neurotransmission. In this study, we investigate the protective effect of taurine against METH-induced neurotoxicity in PC12 cells and the underlying mechanism. The results showed that taurine significantly increased the cell viability inhibited by METH. LC3-II expression was elevated by METH treatment, whereas such increase was obviously attenuated by taurine. Co-treatment of taurine strongly reversed the decline of antioxidase activities induced by METH. Moreover, phosphorylated mammalian target of rapamycin (p-mTOR) was significantly inhibited by METH, whereas complementation of taurine markedly increased the expression of p-mTOR in PC12 cells, rather than phosphorylated Erk. Interestingly, taurine-induced decreasing expression of LC3-II was partially blocked by pretreatment of RAD001, an mTOR inhibitor. These results indicated that taurine inhibits METH-induced autophagic process through activating mTOR rather than Erk signaling. Collectively, our study shows that taurine protects METH-induced PC12 cells damage by attenuating ROS production, apoptosis and autophagy, at least in part, via mTOR signaling pathway. PMID:23041169

  18. In female rats, ethylene glycol treatment elevates protein expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) without inducing hyperoxaluria

    PubMed Central

    Breljak, Davorka; Brzica, Hrvoje; Vrhovac, Ivana; Micek, Vedran; Karaica, Dean; Ljubojević, Marija; Sekovanić, Ankica; Jurasović, Jasna; Rašić, Dubravka; Peraica, Maja; Lovrić, Mila; Schnedler, Nina; Henjakovic, Maja; Wegner, Waja; Burckhardt, Gerhard; Burckhardt, Birgitta C.; Sabolić, Ivan

    2015-01-01

    Aim To investigate whether the sex-dependent expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) changes in a rat model of ethylene glycol (EG)-induced hyperoxaluria. Methods Rats were given tap water (12 males and 12 females; controls) or EG (12 males and 12 females; 0.75% v/v in tap water) for one month. Oxaluric state was confirmed by biochemical parameters in blood plasma, urine, and tissues. Expression of sat-1 and rate-limiting enzymes of oxalate synthesis, alcohol dehydrogenase 1 (Adh1) and hydroxy-acid oxidase 1 (Hao1), was determined by immunocytochemistry (protein) and/or real time reverse transcription polymerase chain reaction (mRNA). Results EG-treated males had significantly higher (in μmol/L; mean ± standard deviation) plasma (59.7 ± 27.2 vs 12.9 ± 4.1, P < 0.001) and urine (3716 ± 1726 vs 241 ± 204, P < 0.001) oxalate levels, and more abundant oxalate crystaluria than controls, while the liver and kidney sat-1 protein and mRNA expression did not differ significantly between these groups. EG-treated females, in comparison with controls had significantly higher (in μmol/L) serum oxalate levels (18.8 ± 2.9 vs 11.6 ± 4.9, P < 0.001), unchanged urine oxalate levels, low oxalate crystaluria, and significantly higher expression (in relative fluorescence units) of the liver (1.59 ± 0.61 vs 0.56 ± 0.39, P = 0.006) and kidney (1.77 ± 0.42 vs 0.69 ± 0.27, P < 0.001) sat-1 protein, but not mRNA. The mRNA expression of Adh1 was female-dominant and that of Hao1 male-dominant, but both were unaffected by EG treatment. Conclusions An increased expression of hepatic and renal oxalate transporting protein sat-1 in EG-treated female rats could protect from hyperoxaluria and oxalate urolithiasis. PMID:26526882

  19. Coordinated Regulation of Hepatic Phase I and II Drug-Metabolizing Genes and Transporters using AhR-, CAR-, PXR-, PPARα-, and Nrf2-Null Mice

    PubMed Central

    Aleksunes, Lauren M.

    2012-01-01

    The transcription factors aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor α (PPARα), and nuclear factor erythroid 2-related factor 2 (Nrf2) regulate genes encoding drug-metabolizing enzymes and transporters in livers of mice after chemical activation. However, the specificity of their transcriptional regulation has not been determined systematically in vivo. The purpose of this study was to identify genes encoding drug-metabolizing enzymes and transporters altered by chemical activators in a transcription factor-dependent manner using wild-type and transcription factor-null mice. Chemical activators were administered intraperitoneally to mice once daily for 4 days. Livers were collected 24 h after the final dose, and total RNA was isolated for mRNA quantification of cytochromes P450, NAD(P)H quinone oxidoreductase 1 (Nqo1), aldehyde dehydrogenases (Aldhs), glutathione transferases (Gsts), sulfotransferases (Sults), UDP-glucuronosyltransferases (Ugts), organic anion-transporting polypeptides (Oatps), and multidrug resistance-associated proteins (Mrps). Pharmacological activation of each transcription factor leads to mRNA induction of drug metabolic and transport genes in livers of male and female wild-type mice, but no change in null mice: AhR (Cyp1a2, Nqo1, Aldh7a1, Ugt1a1, Ugt1a6, Ugt1a9, Ugt2b35, Sult5a1, Gstm3, and Mrp4), CAR (Cyp2b10, Aldh1a1, Aldh1a7, Ugt1a1, Ugt2b34, Sult1e1, Sult3a1, Sult5a1, Papps2, Gstt1, Gsta1, Gsta4, Gstm1–4, and Mrp2–4), PXR (Cyp3a11, Ugt1a1, Ugt1a5, Ugt1a9, Gsta1, Gstm1–m3, Oatp1a4, and Mrp3), PPARα (Cyp4a14, Aldh1a1, mGst3, Gstm4, and Mrp4), and Nrf2 (Nqo1, Aldh1a1, Gsta1, Gsta4, Gstm1–m4, mGst3, and Mrp3–4). Taken together, these data reveal transcription factor specificity and overlap in regulating hepatic drug disposition genes by chemical activators. Coordinated regulation of phase I, phase II, and transport genes by

  20. The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy.

    PubMed

    Eng, Heather; Scialis, Renato J; Rotter, Charles J; Lin, Jian; Lazzaro, Sarah; Varma, Manthena V; Di, Li; Feng, Bo; West, Michael; Kalgutkar, Amit S

    2016-05-01

    Chronic treatment of methicillin-resistantStaphylococcus aureusstrains with the bacteriostatic agent fusidic acid (FA) is frequently associated with myopathy including rhabdomyolysis upon coadministration with statins. Because adverse effects with statins are usually the result of drug-drug interactions, we evaluated the inhibitory effects of FA against human CYP3A4 and clinically relevant drug transporters such as organic anion transporting polypeptides OATP1B1 and OATP1B3, multidrug resistant protein 1, and breast cancer resistance protein, which are involved in the oral absorption and/or systemic clearance of statins including atorvastatin, rosuvastatin, and simvastatin. FA was a weak reversible (IC50= 295 ± 1.0μM) and time-dependent (KI= 216 ± 41μM andkinact= 0.0179 ± 0.001 min(-1)) inhibitor of CYP3A4-catalyzed midazolam-1'-hydroxylase activity in human liver microsomes. FA demonstrated inhibition of multidrug resistant protein 1-mediated digoxin transport with an IC50value of 157 ± 1.0μM and was devoid of breast cancer resistance protein inhibition (IC50> 500μM). In contrast, FA showed potent inhibition of OATP1B1- and OATP1B3-specific rosuvastatin transport with IC50values of 1.59μM and 2.47μM, respectively. Furthermore, coadministration of oral rosuvastatin and FA to rats led to an approximately 19.3-fold and 24.6-fold increase in the rosuvastatin maximum plasma concentration and area under the plasma concentration-time curve, respectively, which could be potentially mediated through inhibitory effects of FA on rat Oatp1a4 (IC50= 2.26μM) and Oatp1b2 (IC50= 4.38μM) transporters, which are responsible for rosuvastatin uptake in rat liver. The potent inhibition of human OATP1B1/OATP1B3 by FA could attenuate hepatic uptake of statins, resulting in increased blood and tissue concentrations, potentially manifesting in musculoskeletal toxicity. PMID:26888941

  1. Taurine supplementation attenuates delayed increase in exercise-induced arterial stiffness.

    PubMed

    Ra, Song-Gyu; Choi, Youngju; Akazawa, Nobuhiko; Ohmori, Hajime; Maeda, Seiji

    2016-06-01

    There is a delayed increase in arterial stiffness after eccentric exercise that is possibly mediated by the concurrent delayed increase in circulating oxidative stress. Taurine has anti-oxidant action, and taurine supplementation may be able to attenuate the increase in oxidative stress after exercise. The purpose of the present study was to investigate whether taurine supplementation attenuates the delayed increase in arterial stiffness after eccentric exercise. In the present double-blind, randomized, and placebo-controlled trial, we divided 29 young, healthy men into 2 groups. Subjects received either 2.0 g of placebo (n = 14) or taurine (n = 15) 3 times per day for 14 days prior to the exercise, on the day of exercise, and the following 3 days. The exercise consisted of 2 sets of 20 maximal-effort eccentric repetitions with the nondominant arm only. On the morning of exercise and for 4 days thereafter, we measured serum malondialdehyde (MDA) and carotid-femoral pulse wave velocity (cfPWV) as indices of oxidative stress and arterial stiffness, respectively. On the third and fourth days after exercise, both MDA and cfPWV significantly increased in the placebo group. However, these elevations were significantly attenuated in the taurine group. The increase in MDA was associated with an increase in cfPWV from before exercise to 4 days after exercise (r = 0.597, p < 0.05) in the placebo group, but not in the taurine group. Our results suggest that delayed increase in arterial stiffness after eccentric exercise was probably affected by the exercise-induced oxidative stress and was attenuated by the taurine supplementation. PMID:27163699

  2. Properties and glial origin of osmotic-dependent release of taurine from the rat supraoptic nucleus.

    PubMed

    Deleuze, C; Duvoid, A; Hussy, N

    1998-03-01

    1. Taurine, prominently concentrated in glial cells in the supraoptic nucleus (SON), is probably involved in the inhibition of SON vasopressin neurones by peripheral hypotonic stimulus, via activation of neuronal glycine receptors. We report here the properties and origin of the osmolarity-dependent release of preloaded [3H]taurine from isolated whole SO nuclei. 2. Hyposmotic medium induced a rapid, reversible and dose-dependent increase in taurine release. Release showed a high sensitivity to osmotic change, with a significant enhancement with less than a 5% decrease in osmolarity. Hyperosmotic stimulus decreased basal release. 3. Evoked release was independent of extracellular Ca2+ and Na+, and was blocked by the Cl- channel blockers DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and DPC (N-phenylanthranilic acid), suggesting a diffusion process through volume-sensitive Cl- channels. 4. Evoked release was transient for large osmotic reductions (> or = 15%), probably reflecting regulatory volume decrease (RVD). However, it was sustained for smaller changes, suggesting that taurine release induced by physiological variations in osmolarity is not linked to RVD. 5. Basal and evoked release were strongly inhibited by an incubation of the tissue with the glia-specific toxin fluorocitrate, but were unaffected by a neurotoxic-treatment with NMDA, demonstrating the glial origin of the release of taurine in the SON. 6. The high osmosensitivity of taurine release suggests an important role in the osmoregulation of the SON function. These results strengthen the notion of an implication of taurine and glial cells in the regulation of the whole-body fluid balance through the modulation of vasopressin release. PMID:9518705

  3. Properties and glial origin of osmotic-dependent release of taurine from the rat supraoptic nucleus

    PubMed Central

    Deleuze, Charlotte; Duvoid, Anne; Hussy, Nicolas

    1998-01-01

    Taurine, prominently concentrated in glial cells in the supraoptic nucleus (SON), is probably involved in the inhibition of SON vasopressin neurones by peripheral hypotonic stimulus, via activation of neuronal glycine receptors. We report here the properties and origin of the osmolarity-dependent release of preloaded [3H]taurine from isolated whole SO nuclei.Hyposmotic medium induced a rapid, reversible and dose-dependent increase in taurine release. Release showed a high sensitivity to osmotic change, with a significant enhancement with less than a 5 % decrease in osmolarity. Hyperosmotic stimulus decreased basal release.Evoked release was independent of extracellular Ca2+ and Na+, and was blocked by the Cl− channel blockers DIDS (4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid) and DPC (N-phenylanthranilic acid), suggesting a diffusion process through volume-sensitive Cl− channels.Evoked release was transient for large osmotic reductions (≥ 15 %), probably reflecting regulatory volume decrease (RVD). However, it was sustained for smaller changes, suggesting that taurine release induced by physiological variations in osmolarity is not linked to RVD.Basal and evoked release were strongly inhibited by an incubation of the tissue with the glia-specific toxin fluorocitrate, but were unaffected by a neurotoxic treatment with NMDA, demonstrating the glial origin of the release of taurine in the SON.The high osmosensitivity of taurine release suggests an important role in the osmoregulation of the SON function. These results strengthen the notion of an implication of taurine and glial cells in the regulation of the whole-body fluid balance through the modulation of vasopressin release. PMID:9518705

  4. Effects of simvastatin and taurine on delayed cerebral vasospasm following subarachnoid hemorrhage in rabbits

    PubMed Central

    LIN, CHENG; ZHAO, YUANLI; WAN, GANG; ZHU, ANLIN; WANG, HAO

    2016-01-01

    The aim of the current study was to observe the effects of simvastatin and taurine on delayed cerebral vasospasm (DCVS) following experimental subarachnoid hemorrhage (SAH) in rabbits. A total of 48 New Zealand white rabbits were allocated at random into four groups (control, SAH, SAH + simvastatin and SAH + taurine groups; n=12 each). The rabbit model of DCVS was established using a double hemorrhage method, which involved injecting autologous arterial blood into the cisterna magna in the SAH groups. The SAH + simvastatin group was administered oral simvastatin (5 mg/kg) daily between days 0–6. The SAH + taurine group was administered oral taurine (50 mg/kg) daily between days 0–6. Starch (50 mg/kg) was administered orally to the animals in the other two groups (control and SAH groups). The control group were not subjected to any other injections or treatment. The internal diameter and internal diameter/wall thickness of the basilar artery (BA) were measured. The expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were determined using immunohistochemical and quantitative polymerase chain reaction methods following the sacrifice of all animals on day 7. The activity of nuclear factor (NF)-κB in the BA was also measured using an electrophoretic mobility shift assay. The BA walls in the SAH + simvastatin and SAH + taurine groups exhibited reduced narrowing and corrugation of the tunica elastica interna compared with the SAH group. At the protein and cDNA levels, it was found that cerebral vasospasm of the BA in the SAH + simvastatin and SAH + taurine groups was alleviated, as indicated by the reduced expression of TNF-α, IL-1β, IL-6 and NF-κB compared with the SAH group (P<0.05). In conclusion, simvastatin and taurine reduced DCVS following SAH in rabbits, which suggests that these compounds may exert anti-inflammatory effects. PMID:27073449

  5. Taurine deficiency is a cause of vigabatrin-induced retinal phototoxicity

    PubMed Central

    Jammoul, Firas; Wang, Qingping; Nabbout, Rimas; Coriat, Caroline; Duboc, Agnès; Simonutti, Manuel; Dubus, Elisabeth; Craft, Cheryl M.; Ye, Wen; Collins, Stephen D.; Dulac, Olivier; Chiron, Catherine; Sahel, José A.; Picaud, Serge

    2008-01-01

    Objective Although vigabatrin irreversibly constricts the visual field, it remains a potent therapy for infantile spasms and a third-line drug for refractory epilepsies. In albino animals, this drug induces a reduction in retinal cell function, retinal disorganisation and cone photoreceptor damage. The objective of this study was to investigate the light dependence of the vigabatrin-elicited retinal toxicity and to screen for molecules preventing this secondary effect of vigabatrin. Methods Rats and mice were treated daily with vigabatrin 40mg and 3mg, respectively. Retinal cell lesions were demonstrated by assessing cell function with electroretinogram measurements, and quantifying retinal disorganization, gliosis and cone cell densities. Results Vigabatrin-elicited retinal lesions were prevented by maintaining animals in darkness during treatment. Different mechanisms including taurine deficiency were reported to produce such phototoxicity; we therefore measured amino acid plasma levels in vigabatrin-treated animals. Taurine levels were 67% lower in vigabatrin-treated animals than in control animals. Taurine supplementation reduced all components of retinal lesions in both rats and mice. Among 6 vigabatrin-treated infants, the taurine plasma level was found to be below normal in three patients and undetectable in two patients. Interpretation These results indicate that vigabatrin generates a taurine deficiency responsible for its retinal phototoxicity. Future studies will investigate whether co-treatment with taurine and vigabatrin can limit epileptic seizures without inducing the constriction of the visual field. Patients on vigabatrin could gain immediate benefit from reduced light exposures and dietetic advice on taurine-rich foods. PMID:19194884

  6. Characterization of taurine binding, uptake, and release in the rat hypothalamus

    SciTech Connect

    Hanretta, A.T.

    1985-01-01

    The neurotransmitter criteria of specific receptors, inactivation, and release were experimentally examined for taurine in the hypothalamus. Specific membrane binding and synaptosomal uptake of taurine both displayed high affinity and low affinity systems. The neurotransmitter criterion of release was studied in superfused synaptosomes. Exposure of synaptosomes which had been preloaded with a concentration of (/sup 3/H)taurine in the high affinity uptake range (1.5 ..mu..M) to either 56 mM K/sup +/ or 100 ..mu..M veratridine evoked a Ca/sup 2 +/-independent release. Exposure of synaptosomes which had been preloaded with a concentration of (/sup 3/H)taurine in the low affinity uptake range (2 mM) to 56 mM K/sup +/ induced a Ca/sup 2 +/-independent release, whereas 100 /sup +/M veratridine did not, either in the presence or absence of Ca/sup 2 +/. Based on these results, as well as other observations, a model is proposed in which the high affinity uptake system is located on neuronal membranes and the low affinity uptake system is located on glial membranes. The mechanisms of binding, uptake, and release in relation to the cellular location of each are discussed. We conclude that the neurotransmitter criterion of activation by re-uptake is satisfied for taurine in the hypothalamus. However, the failure to demonstrate both a specific taurine receptor site and a Ca/sup 2 +/-dependent evoked release, necessitates that we conclude that taurine appears not to function as a hypothalamic neurotransmitter, at least not in the classical sense.

  7. Taurine and cholestasis associated to TPN. Experimental study in rabbit model.

    PubMed

    Moran, J M; Salas, J; Botello, F; Macià, E; Climent, V

    2005-10-01

    Taurine seems to be essential in the newborn for bile acid (BA) tauroconjugation, and its deficiency has been implicated in total parenteral nutrition-associated cholestasis (TPN-AC). Our purpose was to study the relationship between taurine (Ta) and TPN-AC in rabbits, which have a similar biliary metabolism to that of humans. We used 40 young rabbits, fed for 10 days according to the following four groups: GA [10] given TPN, with amino acid solution (AA) but without taurine (Ta) or its AA-precursors (methionine, cysteine, and serine); GB [10] the same but only without taurine; GC [10] the same but with taurine and its precursors; and GD [10] the control group with oral nutrition and saline infusion. Complete blood and bile analytical data were obtained and analyzed, including plasma AA and BA. Liver samples were studied under optical and electron microscopy. Serum: In GC there was a 20% increase in the AA-precursors, but paradoxically it was greater in GA. Bile: In GC there was 30% more excretion of total and free BA compared with less than 20% in GA and GB. Regarding toxic BA, there was a 15% decline in GLC3S excretion, but more than 20% in LCA excretion, than in GA and GB. Moreover, in GC the glyco-/tauro-conjugate ratio was worse than in the other groups. Histomorphology: While in GA and GB liver steatosis was diffuse (microsteatohepatitis type), in GC there was macrosteatosis with mitochondria-surrounded lipid droplets. In GA and GB, the canaliculi appeared dilated, with abundant bile plugs and loss of microvilli. There are signs that taurine may protect against TPN-AC. The mechanism does not seem to be BA tauroconjugation, but probably taurine's antioxidant, membrane stabilization (with Ca2+ and HCO3-), and/or osmotic effects. PMID:16172874

  8. Serum Taurine and Stroke Risk in Women: A Prospective, Nested Case-Control Study

    PubMed Central

    Wu, Fen; Koenig, Karen L.; Zeleniuch-Jacquotte, Anne; Jonas, Saran; Afanasyeva, Yelena; Wójcik, Oktawia P.; Costa, Max; Chen, Yu

    2016-01-01

    Background Taurine (2-aminoethanesulfonic acid), a conditionally essential sulfur-containing amino acid, is mainly obtained from diet in humans. Experimental studies have shown that taurine’s main biological actions include bile salt conjugation, blood pressure regulation, anti-oxidation, and anti-inflammation. Methods We conducted a prospective case-control study nested in the New York University Women’s Health Study, a cohort study involving 14,274 women enrolled since 1985. Taurine was measured in pre-diagnostic serum samples of 241 stroke cases and 479 matched controls. Results There was no statistically significant association between serum taurine and stroke risk in the overall study population. The adjusted ORs for stroke were 1.0 (reference), 0.87 (95% CI, 0.59–1.28), and 1.03 (95% CI, 0.69–1.54) in increasing tertiles of taurine (64.3–126.6, 126.7–152.9, and 153.0–308.5 nmol/mL, respectively). A significant inverse association between serum taurine and stroke risk was observed among never smokers, with an adjusted OR of 0.66 (95% CI, 0.37–1.18) and 0.50 (95% CI, 0.26–0.94) for the second and third tertile, respectively (p for trend = 0.01), but not among past or current smokers (p for interaction < 0.01). Conclusions We observed no overall association between serum taurine and stroke risk, although a protective effect was observed in never smokers, which requires further investigation. Taurine, Stroke, Epidemiology, Prospective, Case-control study, NYUWHS. PMID:26866594

  9. Tyrosine phosphorylation modulates the osmosensitivity of volume-dependent taurine efflux from glial cells in the rat supraoptic nucleus

    PubMed Central

    Deleuze, Charlotte; Duvoid, Anne; Moos, Françoise C; Hussy, Nicolas

    2000-01-01

    In the supraoptic nucleus, taurine, selectively released in an osmodependent manner by glial cells through volume-sensitive anion channels, is likely to inhibit neuronal activity as part of the osmoregulation of vasopressin release. We investigated the involvement of various kinases in the activation of taurine efflux by measuring [3H]taurine release from rat acutely isolated supraoptic nuclei. The protein tyrosine kinase inhibitors genistein and tyrphostin B44 specifically reduced, but did not suppress, both the basal release of taurine and that evoked by a hypotonic stimulus. Inhibition of tyrosine phosphatase by orthovanadate had the opposite effect. The tyrosine kinase and phosphatase inhibitors shifted the relationship between taurine release and medium osmolarity in opposite directions, suggesting that tyrosine phosphorylation modulates the osmosensitivity of taurine release, but is not necessary for its activation. Genistein also increased the amplitude of the decay of the release observed during prolonged hypotonic stimulation. Potentiation of taurine release by tyrosine kinases could serve to maintain a high level of taurine release in spite of cell volume regulation. Taurine release was unaffected by inhibitors and/or activators of PKA, PKC, MEK and Rho kinase. Our results demonstrate a unique regulation by protein tyrosine kinase of the osmosensitivity of taurine efflux in supraoptic astrocytes. This points to the presence of specific volume-dependent anion channels in these cells, or to a specific activation mechanism or regulatory properties. This may relate to the particular role of the osmodependent release of taurine in this structure in the osmoregulation of neuronal activity. PMID:10699075

  10. Tyrosine phosphorylation modulates the osmosensitivity of volume-dependent taurine efflux from glial cells in the rat supraoptic nucleus.

    PubMed

    Deleuze, C; Duvoid, A; Moos, F C; Hussy, N

    2000-03-01

    1. In the supraoptic nucleus, taurine, selectively released in an osmodependent manner by glial cells through volume-sensitive anion channels, is likely to inhibit neuronal activity as part of the osmoregulation of vasopressin release. We investigated the involvement of various kinases in the activation of taurine efflux by measuring [3H]taurine release from rat acutely isolated supraoptic nuclei. 2. The protein tyrosine kinase inhibitors genistein and tyrphostin B44 specifically reduced, but did not suppress, both the basal release of taurine and that evoked by a hypotonic stimulus. Inhibition of tyrosine phosphatase by orthovanadate had the opposite effect. 3. The tyrosine kinase and phosphatase inhibitors shifted the relationship between taurine release and medium osmolarity in opposite directions, suggesting that tyrosine phosphorylation modulates the osmosensitivity of taurine release, but is not necessary for its activation. 4. Genistein also increased the amplitude of the decay of the release observed during prolonged hypotonic stimulation. Potentiation of taurine release by tyrosine kinases could serve to maintain a high level of taurine release in spite of cell volume regulation. 5. Taurine release was unaffected by inhibitors and/or activators of PKA, PKC, MEK and Rho kinase. 6. Our results demonstrate a unique regulation by protein tyrosine kinase of the osmosensitivity of taurine efflux in supraoptic astrocytes. This points to the presence of specific volume-dependent anion channels in these cells, or to a specific activation mechanism or regulatory properties. This may relate to the particular role of the osmodependent release of taurine in this structure in the osmoregulation of neuronal activity. PMID:10699075

  11. Revisiting AFLP fingerprinting for an unbiased assessment of genetic structure and differentiation of taurine and zebu cattle

    PubMed Central

    2014-01-01

    Background Descendants from the extinct aurochs (Bos primigenius), taurine (Bos taurus) and zebu cattle (Bos indicus) were domesticated 10,000 years ago in Southwestern and Southern Asia, respectively, and colonized the world undergoing complex events of admixture and selection. Molecular data, in particular genome-wide single nucleotide polymorphism (SNP) markers, can complement historic and archaeological records to elucidate these past events. However, SNP ascertainment in cattle has been optimized for taurine breeds, imposing limitations to the study of diversity in zebu cattle. As amplified fragment length polymorphism (AFLP) markers are discovered and genotyped as the samples are assayed, this type of marker is free of ascertainment bias. In order to obtain unbiased assessments of genetic differentiation and structure in taurine and zebu cattle, we analyzed a dataset of 135 AFLP markers in 1,593 samples from 13 zebu and 58 taurine breeds, representing nine continental areas. Results We found a geographical pattern of expected heterozygosity in European taurine breeds decreasing with the distance from the domestication centre, arguing against a large-scale introgression from European or African aurochs. Zebu cattle were found to be at least as diverse as taurine cattle. Western African zebu cattle were found to have diverged more from Indian zebu than South American zebu. Model-based clustering and ancestry informative markers analyses suggested that this is due to taurine introgression. Although a large part of South American zebu cattle also descend from taurine cows, we did not detect significant levels of taurine ancestry in these breeds, probably because of systematic backcrossing with zebu bulls. Furthermore, limited zebu introgression was found in Podolian taurine breeds in Italy. Conclusions The assessment of cattle diversity reported here contributes an unbiased global view to genetic differentiation and structure of taurine and zebu cattle

  12. Hepatitis Vaccines

    PubMed Central

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  13. Hepatitis Vaccines.

    PubMed

    Ogholikhan, Sina; Schwarz, Kathleen B

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  14. The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites

    PubMed Central

    Neufeldt, Christopher J.; Joyce, Michael A.; Van Buuren, Nicholas; Levin, Aviad; Kirkegaard, Karla; Gale Jr., Michael; Tyrrell, D. Lorne J.; Wozniak, Richard W.

    2016-01-01

    Hepatitis C virus (HCV) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide. HCV replicates in the cytoplasm, and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures, collectively termed the membranous web (MW). The MW contains the sites of viral replication and assembly, and we have identified distinct membrane fractions derived from HCV-infected cells that contain replication and assembly complexes enriched for viral RNA and infectious virus, respectively. The complex membrane structure of the MW is thought to protect the viral genome limiting its interactions with cytoplasmic pattern recognition receptors (PRRs) and thereby preventing activation of cellular innate immune responses. Here we show that PRRs, including RIG-I and MDA5, and ribosomes are excluded from viral replication and assembly centers within the MW. Furthermore, we present evidence that components of the nuclear transport machinery regulate access of proteins to MW compartments. We show that the restricted assess of RIG-I to the MW can be overcome by the addition of a nuclear localization signal sequence, and that expression of a NLS-RIG-I construct leads to increased immune activation and the inhibition of viral replication. PMID:26863439

  15. The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites.

    PubMed

    Neufeldt, Christopher J; Joyce, Michael A; Van Buuren, Nicholas; Levin, Aviad; Kirkegaard, Karla; Gale, Michael; Tyrrell, D Lorne J; Wozniak, Richard W

    2016-02-01

    Hepatitis C virus (HCV) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide. HCV replicates in the cytoplasm, and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures, collectively termed the membranous web (MW). The MW contains the sites of viral replication and assembly, and we have identified distinct membrane fractions derived from HCV-infected cells that contain replication and assembly complexes enriched for viral RNA and infectious virus, respectively. The complex membrane structure of the MW is thought to protect the viral genome limiting its interactions with cytoplasmic pattern recognition receptors (PRRs) and thereby preventing activation of cellular innate immune responses. Here we show that PRRs, including RIG-I and MDA5, and ribosomes are excluded from viral replication and assembly centers within the MW. Furthermore, we present evidence that components of the nuclear transport machinery regulate access of proteins to MW compartments. We show that the restricted assess of RIG-I to the MW can be overcome by the addition of a nuclear localization signal sequence, and that expression of a NLS-RIG-I construct leads to increased immune activation and the inhibition of viral replication. PMID:26863439

  16. Positive Regulatory Control Loop between Gut Leptin and Intestinal GLUT2/GLUT5 Transporters Links to Hepatic Metabolic Functions in Rodents

    PubMed Central

    Sakar, Yassine; Nazaret, Corinne; Lettéron, Philippe; Ait Omar, Amal; Avenati, Mathilde; Viollet, Benoît; Ducroc, Robert; Bado, André

    2009-01-01

    Background and Aims The small intestine is the major site of absorption of dietary sugars. The rate at which they enter and exit the intestine has a major effect on blood glucose homeostasis. In this study, we determine the effects of luminal leptin on activity/expression of GLUT2 and GLUT5 transporters in response to sugars intake and analyse their physiological consequences. Methodology Wistar rats, wild type and AMPKα2−/− mice were used. In vitro and in vivo isolated jejunal loops were used to quantify transport of fructose and galactose in the absence and the presence of leptin. The effects of fructose and galactose on gastric leptin release were determined. The effects of leptin given orally without or with fructose were determined on the expression of GLUT2/5, on some gluconeogenesis and lipogenic enzymes in the intestine and the liver. Principal Findings First, in vitro luminal leptin activating its receptors coupled to PKCβII and AMPKα, increased insertion of GLUT2/5 into the brush-border membrane leading to enhanced galactose and fructose transport. Second in vivo, oral fructose but not galactose induced in mice a rapid and potent release of gastric leptin in gastric juice without significant changes in plasma leptin levels. Moreover, leptin given orally at a dose reproducing comparable levels to those induced by fructose, stimulated GLUT5-fructose transport, and potentiated fructose-induced: i) increase in blood glucose and mRNA levels of key gluconeogenesis enzymes; ii) increase in blood triglycerides and reduction of mRNA levels of intestinal and hepatic Fasting-induced adipocyte factor (Fiaf) and iii) increase in SREBP-1c, ACC-1, FAS mRNA levels and dephosphorylation/activation of ACC-1 in liver. Conclusion/Significance These data identify for the first time a positive regulatory control loop between gut leptin and fructose in which fructose triggers release of gastric leptin which, in turn, up-regulates GLUT5 and concurrently modulates

  17. Dried-Plasma Transport Using a Novel Matrix and Collection System for Human Immunodeficiency Virus and Hepatitis C Virus Virologic Testing▿

    PubMed Central

    Lloyd, R. M.; Burns, D. A.; Huong, J. T.; Mathis, R. L.; Winters, M. A.; Tanner, M.; De La Rosa, A.; Yen-Lieberman, B.; Armstrong, W.; Taege, A.; McClernon, D. R.; Wetshtein, J. L.; Friedrich, Brian M.; Ferguson, Monique R.; O'Brien, William; Feorino, P. M.; Holodniy, M.

    2009-01-01

    A novel method for the collection and transportation of dried-blood-plasma samples, SampleTanker (ST), was developed and compared to standard shipping protocols for frozen-plasma specimens containing human immunodeficiency virus type 1 (HIV-1) and/or hepatitis C virus (HCV). Matched frozen and dried 1-ml EDTA-containing plasma samples were collected and analyzed by several molecular-based virologic assays. After addition of 1.175 ml of reconstitution buffer, 1.035 ml of dried plasma was recovered. Mean intra-assay variances were 0.05, 0.05, and 0.06 log10 copies/ml for the Versant, Amplicor, and NucliSens QT HIV-1 load assays, respectively (P, not significant). However, mean HIV-1 viral load was consistently reduced in dried samples by 0.32 to 0.51 log10 copies/ml, depending on assay type (P < 0.05). Infectious HIV-1 was not recovered from dried ST plasma. There was no significant difference in HIV-1 viral load results obtained using ST after 8 weeks of storage at ambient temperature. Compared to frozen plasma, HIV-1 genotypic results were >99% concordant at the nucleotide and amino acid levels, as well as for resistance-associated mutations. We further demonstrated successful detection of multiple analytes, including HIV-1 viral load, HIV-1 antiretroviral resistance genotype, and HCV genotype, from a single ST unit. Dried plasma collected with ST yielded comparable results to frozen samples for multiple-analyte clinical testing. As such, ST could be a useful alternative for virologic tests and clinical trials worldwide by significantly diminishing transportation cost and the sample volume restrictions associated with dried-blood-spot technology. PMID:19321732

  18. Hepatitis B Vaccine

    MedlinePlus

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis B?Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. ...

  19. Hepatitis A Vaccine

    MedlinePlus

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis A?Hepatitis A is a serious liver disease caused by the hepatitis A virus (HAV). HAV is found in ...

  20. Hepatitis C: Clinical Trials

    MedlinePlus

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  1. Autoimmune hepatitis

    MedlinePlus

    ... diseases. These include: Graves disease Inflammatory bowel disease Rheumatoid arthritis Scleroderma Sjogren syndrome Systemic lupus erythematosus Thyroiditis Type 1 diabetes Ulcerative colitis Autoimmune hepatitis may occur in family ...

  2. Hepatitis B

    MedlinePlus

    ... A Hepatitis B HPV (Human Papillomavirus) Influenza (Flu) Measles Meningococcal Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) Professional Resources Adult ...

  3. Protective role of taurine against morphine-induced neurotoxicity in C6 cells via inhibition of oxidative stress.

    PubMed

    Zhou, Jiaqing; Li, Yan; Yan, Guangyan; Bu, Qian; Lv, Lei; Yang, Yanzhu; Zhao, Jinxuan; Shao, Xue; Deng, Yi; Zhu, Ruimin; Zhao, Yinglan; Cen, Xiaobo

    2011-11-01

    This study was carried out to investigate the protective role of taurine (2-aminoethanesulphonicacid) against morphine-induced neurotoxicity in C6 cells. It was found that taurine significantly increased the viability of C6 cells treated by morphine, showing the neuroprotective role against morphine-induced neurotoxicity. However, such neuroprotective effect of taurine could not be blocked by bicuculline, an antagonist of gamma-amino butyrate (GABA) receptor. To determine the oxidative damage induced by morphine, the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured in C6 cells. The decreased activities of SOD, CAT, and GPx in C6 cells were observed after morphine treatment for 48 h. However, taurine administration effectively ameliorated morphine-induced oxidative insult. To estimate anti-apoptosis effect of taurine, flow cytometry analysis as well as detection for caspase-3 and Bcl-2 expressions was performed after morphine exposure for 48 h. It was found that Bcl-2 expression was down regulated by morphine, whereas taurine could reverse morphine-induced decrease in Bcl-2 expression. Taurine showed no effect on caspase-3 expression. Collectively, the results show that taurine possesses the capability to ameliorate morphine-induced oxidative insult and apoptosis in C6 cells, probably due to its antioxidant activity rather than activation of GABA receptors. PMID:21611853

  4. Taurine release by astrocytes modulates osmosensitive glycine receptor tone and excitability in the adult supraoptic nucleus.

    PubMed

    Choe, Katrina Y; Olson, James E; Bourque, Charles W

    2012-09-01

    Cells can release the free amino acid taurine through volume-regulated anion channels (VRACs), and it has been hypothesized that taurine released from glial cells is capable of inhibiting action potential (AP) firing by activating neuronal glycine receptors (GlyRs) (Hussy et al., 1997). Although an inhibitory GlyR tone is widely observed in the brain, it remains unknown whether this specifically reflects gliotransmission because most neurons also express VRACs and other endogenous molecules can activate GlyRs. We found that VRACs are absent in neurons of the rat supraoptic nucleus (SON), suggesting that glial cells are the exclusive source of taurine in this nucleus. Application of strychnine to rat hypothalamic explants caused a depolarization of SON neurons associated with a decrease of chloride conductance and could excite these cells in the absence of fast synaptic transmission. This inhibitory GlyR tone was eliminated by pharmacological blockade of VRACs, by cellular taurine depletion, by metabolic inactivation of glia with fluorocitrate, and after retraction of astrocytic processes that intercalate neuronal somata and dendrites. Finally, GlyR tone varied inversely with extracellular fluid tonicity to mediate the osmotic control of AP firing by SON neurons. These findings establish taurine as a physiological gliotransmitter and show that gliotransmission is a spatially constrained process that can be modulated by the morphological rearrangement of astrocytes. PMID:22956842

  5. The role of taurine in diabetes and the development of diabetic complications.

    PubMed

    Hansen, S H

    2001-01-01

    The ubiquitously found beta-amino acid taurine has several physiological functions, e.g. in bile acid formation, as an osmolyte by cell volume regulation, in the heart, in the retina, in the formation of N-chlorotaurine by reaction with hypochlorous acid in leucocytes, and possibly for intracellular scavenging of carbonyl groups. Some animals, such as the cat and the C57BL/6 mouse, have disturbances in taurine homeostasis. The C57BL/6 mouse strain is widely used in diabetic and atherosclerotic animal models. In diabetes, the high extracellular levels of glucose disturb the cellular osmoregulation and sorbitol is formed intracellularly due to the intracellular polyol pathway, which is suspected to be one of the key processes in the development of diabetic late complications and associated cellular dysfunctions. Intracellular accumulation of sorbitol is most likely to cause depletion of other intracellular compounds including osmolytes such as myo-inositol and taurine. When considering the clinical complications in diabetes, several links can be established between altered taurine metabolism and the development of cellular dysfunctions in diabetes which cause the clinical complications observed in diabetes, e.g. retinopathy, neuropathy, nephropathy, cardiomyopathy, platelet aggregation, endothelial dysfunction and atherosclerosis. Possible therapeutic perspectives could be a supplementation with taurine and other osmolytes and low-molecular compounds, perhaps in a combinational therapy with aldose reductase inhibitors. PMID:11747139

  6. Effect of Taurine on Hemodiafiltration in Patients With Chronic Heart Failure.

    PubMed

    Shiohira, Shunji; Komatsu, Mizuki; Okazaki, Masayuki; Naganuma, Toshiaki; Kawaguchi, Hiroshi; Nitta, Kosaku; Tsuchiya, Ken

    2016-02-01

    Taurine, an important factor in the living body, is essential for cardiovascular function and development and function of skeletal muscle, retina and central nervous system. In the present study, its effect on cardiovascular function was specifically taken into consideration. In hemodiafiltration (HDF) patients, the effect of taurine on patients with chronic heart failure (CHF), in whom dry weight was difficult to control, was evaluated. All patients who were subjected to regular HDF for 4 h three times per week at Joban hospital were included in this study. Patients with chronic heart failure, in whom dry weight was difficult to control (N = 4), were included in the evaluation of clinical status. X-ray and echocardiography were determined before and after taurine treatment. Almost all patients were taking nitric acid, warfarin, anti-platelet agents and vasopressors. Because vital signs were unstable in chronic heart failure, all cases withheld antihypertensive drugs during HDF. For unstable vital signs during HDF, pulmonary congestion was chronically recognized. After taurine was started, vital signs stabilized and lowering of dry weight was possible. In addition, X-ray and cardiac diastolic failure on echocardiography improved. Taurine was effective for CHF patients on HDF in whom dry weight was difficult to control in spite of various medications. PMID:26712423

  7. The Effect of Supplemental Dietary Taurine on Tinnitus and Auditory Discrimination in an Animal Model

    PubMed Central

    Brozoski, Thomas J.; Caspary, Donald M.; Bauer, Carol A.; Richardson, Benjamin D.

    2010-01-01

    Loss of central inhibition has been hypothesized to underpin tinnitus and impact auditory acuity. Taurine, a partial agonist at inhibitory glycine and γ-amino butyric acid receptors, was added to the daily diet of rats to examine its effects on chronic tinnitus and normal auditory discrimination. Eight rats were unilaterally exposed once to a loud sound to induce tinnitus. The rats were trained and tested in an operant task shown to be sensitive to tinnitus. An equivalent unexposed control group was run in parallel. Months after exposure, 6 of the exposed rats showed significant evidence of chronic tinnitus. Two concentrations of taurine in drinking water were given over several weeks (attaining average daily doses of 67 mg/kg and 294 mg/kg). Water consumption was unaffected. Three main effects were obtained: (1) The high taurine dose significantly attenuated tinnitus, which returned to near pre-treatment levels following washout. (2) Auditory discrimination was significantly improved in unexposed control rats at both doses. (3) As indicated by lever pressing, taurine at both doses had a significant group-equivalent stimulant effect. These results are consistent with the hypothesis that taurine attenuates tinnitus and improves auditory discrimination by increasing inhibitory tone and decreasing noise in the auditory pathway. PMID:20868734

  8. Neuroprotection of taurine against reactive oxygen species is associated with inhibiting NADPH oxidases.

    PubMed

    Han, Zhou; Gao, Li-Yan; Lin, Yu-Hui; Chang, Lei; Wu, Hai-Yin; Luo, Chun-Xia; Zhu, Dong-Ya

    2016-04-15

    It is well established that taurine shows potent protection against glutamate-induced injury to neurons in stroke. The neuroprotection may result from multiple mechanisms. Increasing evidences suggest that NADPH oxidases (Nox), the primary source of superoxide induced by N-methyl-d-aspartate (NMDA) receptor activation, are involved in the process of oxidative stress. We found that 100μM NMDA induced oxidative stress by increasing the reactive oxygen species level, which contributed to the cell death, in vitro. Neuron cultures pretreated with 25mM taurine showed lower percentage of death cells and declined reactive oxygen species level. Moreover, taurine attenuated Nox2/Nox4 protein expression and enzyme activity and declined intracellular calcium intensity during NMDA-induced neuron injury. Additionally, taurine also showed neuroprotection against H2O2-induced injury, accompanying with Nox inhibition. So, we suppose that protection of taurine against reactive oxygen species during NMDA-induced neuron injury is associated with Nox inhibition, probably in a calcium-dependent manner. PMID:26945820

  9. Effect of Oral Taurine on Morbidity and Mortality in Elderly Hip Fracture Patients: A Randomized Trial

    PubMed Central

    Van Stijn, Mireille F. M.; Bruins, Arnoud A.; Vermeulen, Mechteld A. R.; Witlox, Joost; Teerlink, Tom; Schoorl, Margreet G.; De Bandt, Jean Pascal; Twisk, Jos W. R.; Van Leeuwen, Paul A. M.; Houdijk, Alexander P. J.

    2015-01-01

    Hip fracture patients represent a large part of the elderly surgical population and face severe postoperative morbidity and excessive mortality compared to adult surgical hip fracture patients. Low antioxidant status and taurine deficiency is common in the elderly, and may negatively affect postoperative outcome. We hypothesized that taurine, an antioxidant, could improve clinical outcome in the elderly hip fracture patient. A double blind randomized, placebo controlled, clinical trial was conducted on elderly hip fracture patients. Supplementation started after admission and before surgery up to the sixth postoperative day. Markers of oxidative status were measured during hospitalization, and postoperative outcome was monitored for one year after surgery. Taurine supplementation did not improve in-hospital morbidity, medical comorbidities during the first year, or mortality during the first year. Taurine supplementation lowered postoperative oxidative stress, as shown by lower urinary 8-hydroxy-2-deoxyguanosine levels (Generalized estimating equations (GEE) analysis average difference over time; regression coefficient (Beta): −0.54; 95% CI: −1.08–−0.01; p = 0.04), blunted plasma malondialdehyde response (Beta: 1.58; 95% CI: 0.00–3.15; p = 0.05) and a trend towards lower lactate to pyruvate ratio (Beta: −1.10; 95% CI: −2.33–0.12; p = 0.08). We concluded that peri-operative taurine supplementation attenuated postoperative oxidative stress in elderly hip fracture patients, but did not improve postoperative morbidity and mortality. PMID:26035756

  10. γ-Aminobutyric Acid Transporter 2 Mediates the Hepatic Uptake of Guanidinoacetate, the Creatine Biosynthetic Precursor, in Rats

    PubMed Central

    Tachikawa, Masanori; Ikeda, Saori; Fujinawa, Jun; Hirose, Shirou; Akanuma, Shin-ichi; Hosoya, Ken-ichi

    2012-01-01

    Guanidinoacetic acid (GAA) is the biosynthetic precursor of creatine which is involved in storage and transmission of phosphate-bound energy. Hepatocytes readily convert GAA to creatine, raising the possibility that the active uptake of GAA by hepatocytes is a regulatory factor. The purpose of this study is to investigate and identify the transporter responsible for GAA uptake by hepatocytes. The characteristics of [14C]GAA uptake by hepatocytes were elucidated using the in vivo liver uptake method, freshly isolated rat hepatocytes, an expression system of Xenopus laevis oocytes, gene knockdown, and an immunohistochemical technique. In vivo injection of [14C]GAA into the rat femoral vein and portal vein results in the rapid uptake of [14C]GAA by the liver. The uptake was markedly inhibited by γ-aminobutyric acid (GABA) and nipecotinic acid, an inhibitor of GABA transporters (GATs). The characteristics of Na+- and Cl−-dependent [14C]GAA uptake by freshly isolated rat hepatocytes were consistent with those of GAT2. The Km value of the GAA uptake (134 µM) was close to that of GAT2-mediated GAA transport (78.9 µM). GABA caused a marked inhibition with an IC50 value of 8.81 µM. The [14C]GAA uptake exhibited a significant reduction corresponding to the reduction in GAT2 protein expression. GAT2 was localized on the sinusoidal membrane of the hepatocytes predominantly in the periportal region. This distribution pattern was consistent with that of the creatine biosynthetic enzyme, S-adenosylmethionine∶guanidinoacetate N-methyltransferase. GAT2 makes a major contribution to the sinusoidal GAA uptake by periportal hepatocytes, thus regulating creatine biosynthesis in the liver. PMID:22384273

  11. γ-Aminobutyric acid transporter 2 mediates the hepatic uptake of guanidinoacetate, the creatine biosynthetic precursor, in rats.

    PubMed

    Tachikawa, Masanori; Ikeda, Saori; Fujinawa, Jun; Hirose, Shirou; Akanuma, Shin-ichi; Hosoya, Ken-ichi

    2012-01-01

    Guanidinoacetic acid (GAA) is the biosynthetic precursor of creatine which is involved in storage and transmission of phosphate-bound energy. Hepatocytes readily convert GAA to creatine, raising the possibility that the active uptake of GAA by hepatocytes is a regulatory factor. The purpose of this study is to investigate and identify the transporter responsible for GAA uptake by hepatocytes. The characteristics of [(14)C]GAA uptake by hepatocytes were elucidated using the in vivo liver uptake method, freshly isolated rat hepatocytes, an expression system of Xenopus laevis oocytes, gene knockdown, and an immunohistochemical technique. In vivo injection of [(14)C]GAA into the rat femoral vein and portal vein results in the rapid uptake of [(14)C]GAA by the liver. The uptake was markedly inhibited by γ-aminobutyric acid (GABA) and nipecotinic acid, an inhibitor of GABA transporters (GATs). The characteristics of Na(+)- and Cl(-)-dependent [(14)C]GAA uptake by freshly isolated rat hepatocytes were consistent with those of GAT2. The Km value of the GAA uptake (134 µM) was close to that of GAT2-mediated GAA transport (78.9 µM). GABA caused a marked inhibition with an IC(50) value of 8.81 µM. The [(14)C]GAA uptake exhibited a significant reduction corresponding to the reduction in GAT2 protein expression. GAT2 was localized on the sinusoidal membrane of the hepatocytes predominantly in the periportal region. This distribution pattern was consistent with that of the creatine biosynthetic enzyme, S-adenosylmethionine:guanidinoacetate N-methyltransferase. GAT2 makes a major contribution to the sinusoidal GAA uptake by periportal hepatocytes, thus regulating creatine biosynthesis in the liver. PMID:22384273

  12. Hepatic handling of a synthetic gamma-labeled bile acid (/sup 75/SeHCAT)

    SciTech Connect

    Galatola, G.; Jazrawi, R.P.; Bridges, C.; Joseph, A.E.; Northfield, T.C.

    1988-03-01

    /sup 75/Se-homocholic acid-taurine (/sup 75/SeHCAT) is the first available gamma-labeled bile acid, and should therefore be handled more efficiently and specifically by the liver than previous hepatoscintigraphic agents. We have measured serum and hepatic kinetics for /sup 75/SeHCAT, and compared them with those for the conventional hepatobiliary scintigraphic agent 99mTc-hepatoiminodiacetic acid, and with serum kinetics for the corresponding natural bile acid, (/sup 14/C)cholic acid-taurine. We used a dynamic scintigraphic technique and serial blood sampling in 8 subjects. Initial hepatic uptake rate was identical to initial serum disappearance rate (14% dose/min) for /sup 75/SeHCAT, but significantly lower for 99mTc-hepatoiminodiacetic acid (6% vs. 14% dose/min, p less than 0.001). Hepatic transit time was shorter for /sup 75/SeHCAT (13 min vs. 22 min, p less than 0.02), net hepatic excretory rate was more rapid (1.4% vs. 0.8% dose/min, p less than 0.001), and urinary excretion was lower (1.0% vs. 9.0% dose, p less than 0.001). Initial and late-plasma disappearance rates were significantly lower for /sup 75/SeHCAT (14.3% and 1.5% dose/min) than for (/sup 14/C)cholic acid-taurine (21.3% and 2.8% dose/min, respectively), and plasma clearance was also lower (2/sup 75/ vs. 670 ml/min). In vitro, /sup 75/SeHCAT was bound to serum proteins more completely than (/sup 14/C)cholic acid-taurine (90.4% vs. 86.5%, p less than 0.005). We conclude that /sup 75/SeHCAT provides a hepatoscintigraphic agent that is handled more efficiently and specifically by the liver than the conventionally used agent 99mTc-hepatoiminodiacetic acid. It is not cleared from the serum as rapidly as (/sup 14/C)cholic acid-taurine, probably due to its stronger protein binding. The clinical value of /sup 75/SeHCAT in assessing liver disease should be investigated.

  13. Antioxidant properties of taurine in rat alveolar macrophages

    SciTech Connect

    Castranova, V.; Banks, M.A.; Porter, D.W.; Martin, W.G. West Virginia Univ., Morgantown )

    1990-02-26

    Isolated rat alveolar macrophages (RAM) which had taken-up and accumulated extracellular (0-500 {mu}M) taurine (TAU) were exposed to 0.45 {plus minus} 0.05 ppm ozone for 30 minutes in a modified tissue culture flask containing TAU-supplemented medium. Recovered cells were assayed for oxidant damage and media analyzed for leakage of intracellular components. Cell viability significantly increased, while recovery of cells decreased (possibly due to increased adherence) with increasing TAU. At 100 {mu}M (rat plasma TAU level), TAU protected against the ozone-induced increase in zymosan-stimulated chemiluminescence, diminished leakages of lipid peroxidation products and protein into the medium, and partially restored the ozone-inactivated Na{sup +}/K{sup +} ATPase activity of RAM. Efflux of oxidized glutathione was maximized and K{sup +} leakage was minimized by the addition of 250 {mu}M TAU. At 250-500 {mu}M TAU, leakages of lipid peroxidation products and protein were enhanced, while the intracellular TAU content dramatically increased. These results indicate that TAU has both direct and indirect antioxidant properties at low levels and pro-oxidant properties at high levels in RAM.

  14. Hypochlorous acid and taurine-N-monochloramine in periodontal diseases.

    PubMed

    Mainnemare, A; Mégarbane, B; Soueidan, A; Daniel, A; Chapple, I L C

    2004-11-01

    Chronic periodontitis is a multi-factorial disease involving anaerobic bacteria and the generation of an inflammatory response, including the production of metalloproteinases, pro-inflammatory cytokines, and eicosanoids. Hypochlorous acid (HOCl) and taurine-N-monochloramine (TauCl) are the end-products of the neutrophilic polymorphonuclear leukocyte (PMN) respiratory burst. They act synergistically to modulate the inflammatory response. In the extracellular environment, HOCl and TauCl may directly neutralize interleukin 6 (IL-6) and several metalloproteinases, while HOCl increases the capacity of alpha(2)-macroglobulin to bind Tumor Necrosis Factor-alpha, IL-2, and IL-6, and facilitates the release of various growth factors. TauCl inhibits the production of inflammatory mediators, prostaglandins, and nitric oxide. HOCl activates tyrosine kinase signaling cascades, generating an increase in the production of extracellular matrix components, growth factors, and inflammatory mediators. Thus, HOCl and TauCl appear to play a crucial role in the periodontal inflammatory process. Taken together, these findings may offer opportunities for the development of novel host-modulating therapies for the treatment of periodontitis. PMID:15505230

  15. Eye Findings on Vigabatrin and Taurine Treatment in Two Patients with Succinic Semialdehyde Dehydrogenase Deficiency.

    PubMed

    Horvath, Gabriella-Ana; Hukin, Juliette; Stockler-Ipsiroglu, Sylvia G; Aroichane, Maryam

    2016-08-01

    We describe for the first time two patients with succinic semialdehyde dehydrogenase (SSADH) deficiency, who were found to have abnormal electroretinogram (ERG) examinations at baseline, or 6 months after vigabatrin treatment was started. This was somewhat reversible with L-taurine treatment, or minimally progressive. The mechanism of injury to the retina may be induced by elevations of γ-aminobutyric acid causing peripheral photoreceptor and ganglion cell damage, and this can be exacerbated by the use of vigabatrin. The use of taurine supplementation in tandem with vigabatrin may allow reversal of retinopathy and mitigate or slow down further deterioration. Further prospective clinical trials are required to evaluate this further. We recommend starting L-taurine therapy together with vigabatrin if a trial of vigabatrin is commenced in a patient with SSADH deficiency. Close monitoring of visual fields or ERG is also recommended at baseline and during vigabatrin therapy. PMID:27104484

  16. Simultaneous Spectral Editing for γ-Aminobutyric Acid and Taurine Using Double Quantum Coherence Transfer

    NASA Astrophysics Data System (ADS)

    Lei, Hao; Peeling, James

    2000-03-01

    Conventional double quantum (DQ) editing techniques recover resonances of one metabolite at a time and are thus inefficient for monitoring metabolic changes involving several metabolites. A DQ coherence transfer double editing sequence using a dual-band DQ coherence read pulse is described here. The sequence permits simultaneous spectral editing for two metabolites with similar J coupling constants in a single scan. Simultaneous editing for taurine and γ-aminobutyric acid (GABA) is demonstrated using solution phantoms and rat brain tissue. Selectivity of the double editing sequence for the target metabolites is as good as that achieved using conventional DQ editing which selects each metabolite individually. With experimental parameters of the double editing sequence chosen to optimize GABA editing, the sensitivity for GABA detection is the same as that with GABA editing only, while the sensitivity for taurine detection is decreased slightly compared to that with taurine editing only.

  17. Molecular characterization of a bovine Y-specific DNA sequence conserved in taurine and zebu breeds.

    PubMed

    Alves, Beatriz C A; Mayer, Mário G; Taber, Anna Paula; Egito, Andréa A; Fagundes, Valéria; McElreavey, Ken; Moreira-Filho, Carlos A

    2006-06-01

    The identification of new bovine male-specific DNA sequences is of great interest because the bovine Y chromosome remains poorly characterized in terms of physical and genetic maps. Since taurine and zebu Y chromosomes are structurally different, the identification of Y-specific sequences present in both sub-species is particularly important: these sequences are of evolutionary significance and can be broadly used for embryo sexing. In this work, we initially used the random amplified polymorphic DNA (RAPD) technique to search for male-specific sequences present as monomorphic markers in genomic DNA from zebu and taurine bulls. A male-specific RAPD band was found to be present and highly conserved in both sub-species, as demonstrated by Southern blotting, fluorescent in situ hybridization (FISH) and DNA sequencing. In a previous work, a pair of primers derived from this marker was successfully used in taurine and zebu embryo sexing. PMID:17286047

  18. Effects of taurine on cadmium exposure in muscle, gill, and bone tissues of Carassius auratus

    PubMed Central

    Yoo, Il-Su; Shin, Kyung-Ok; Chung, Keun-Hee

    2013-01-01

    This study was performed in order to investigate the effects of taurine on cadmium poisoning in muscle, gill, and bone tissues of wild goldfish. For this experiment, 80 wild goldfish were divided into four experimental groups: 0.3 mg/L of cadmium and 0 mg/L of taurine (Group I), 0.3 mg/L of cadmium and 20 mg/kg of taurine (Group II), 0.3 mg/L of cadmium and 40 mg/L of taurine (Group III), and 0.3 mg/L of cadmium and 80 mg/L of taurine (Group IV). The results were as follows: The cadmium concentration in muscle tissue of wild goldfish was 0.65-3.21 mg/kg wet wt in Group I, whereas it decreased in Group IV. Levels of cadmium in gill tissue of wild goldfish were 16.57-42.39 mg/kg wet wt in Group I, 15.23-43.01 mg/kg wet wt in Group II, 15.11-39.56 mg/kg wet wt in Group III, and 13.15-38.55 mg/kg wet wt in Group IV (P < 0.05), suggesting that the cadmium concentration decreased in the experimental groups compared to control. The cadmium concentration in bone tissue of wild goldfish after 28 days was 0.52-9.75 mg/kg in Group II, whereas it increased in Group III (P < 0.05). In conclusion, taurine may have a preventive effect against cadmium accumulation in biological tissues. PMID:23423777

  19. Post-operative monitoring of cortical taurine in patients with subarachnoid hemorrhage: a microdialysis study.

    PubMed

    De Micheli, E; Pinna, G; Alfieri, A; Caramia, G; Bianchi, L; Colivicchi, M A; Della Corte, L; Bricolo, A

    2000-01-01

    Intracerebral MD enables the retrieval of endogenous substances from the extracellular fluid (ECF) of the brain and has been demonstrated to be a sensitive technique for early detection of subtle vasospasm-induced neurometabolic abnormalities in patients with subarachnoid hemorrhage (SAH). The aim of this study was to monitor cortical extracellular concentrations of energy metabolism markers, such as glucose and lactate, neurotransmitter amino acids, such as glutamate, aspartate, GABA and taurine to identify any neurochemical patterns of cerebral ischemia. A prospective clinical study was conducted on a group of 16 patients with non-severe SAH operated on within 72 hours after initial bleeding. Following aneurysm clipping, an MD catheter was inserted in the cortical region where vasospasm could be expected to develop, and perfused with artificial CSF at 0.3 microl/min flow rate. Dialysate was collected every 6 hours and then analyzed on High Performance Liquid Cromatography (HPLC) for glucose, lactate, pyruvate, glutamate, aspartate, GABA and taurine. Mean ECF taurine concentrations ranged from 1.4 + 0.7 to 12.3 + 7.8 micromol/l in single patients: global mean value was 5.8 + 3.8 micromol/l. In this series, the highest absolute taurine value was 25.7 micromol/l, observed in a patient who developed clinical and radiological signs of cerebral ischemia. Nine patients presented clinical disturbances related to cerebral vasospasm. In this setting, representing a mild-to-moderate hypoxic condition, MD data demonstrated that lactate is the most sensitive marker of cellular energy imbalance. Increased lactate levels positively correlated with glutamate (P<0.0001), aspartate (P<0.0001), GABA (P<0.0001) and taurine (P<0.0001) concentrations. These results suggest that also in humans increased taurine levels reflect a condition of cellular stress. This study confirms that MD is a sensitive technique to reveal subtle metabolic abnormalities possibly resulting in cell damage

  20. Detection of Taurine in Biological Tissues by 33S NMR Spectroscopy

    NASA Astrophysics Data System (ADS)

    Musio, Roberta; Sciacovelli, Oronzo

    2001-12-01

    The potential of 33S NMR spectroscopy for biochemical investigations on taurine (2-aminoethanesulfonic acid) is explored. It is demonstrated that 33S NMR spectroscopy allows the selective and unequivocal identification of taurine in biological samples. 33S NMR spectra of homogenated and intact tissues are reported for the first time, together with the spectrum of a living mollusc. Emphasis is placed on the importance of choosing appropriate signal processing methods to improve the quality of the 33S NMR spectra of biological tissues.

  1. Spectral Editing Technique for the in Vitroand in VivoDetection of Taurine

    NASA Astrophysics Data System (ADS)

    Hardy, D. L.; Norwood, T. J.

    1998-07-01

    In vivo1H NMR spectroscopy has proven to be a useful noninvasive tool for the investigation of numerous metabolic and physiological states. Taurine is potentially a useful indicator in neonate development and is involved in a number of physiological processes. However, it could not previously be observed in thein vivo1H spectrum because of overlap with adjacent resonances. We have developed a spectral editing technique based upon double quantum filtration which allows the taurine resonances to be resolved from adjacent peaks. The experiment is demonstrated both on perchloric acid rodent brain extract and on rodent brain homogenate.

  2. Caffeamide 36-13 Regulates the Antidiabetic and Hypolipidemic Signs of High-Fat-Fed Mice on Glucose Transporter 4, AMPK Phosphorylation, and Regulated Hepatic Glucose Production

    PubMed Central

    Kuo, Yueh-Hsiung; Lin, Cheng-Hsiu; Shih, Chun-Ching

    2014-01-01

    This study was to investigate the antidiabetic and antihyperlipidemic effects of (E)-3-[3, 4-dihydroxyphenyl-1-(piperidin-1-yl)prop-2-en-1-one] (36-13) (TS), one of caffeic acid amide derivatives, on high-fat (HF-) fed mice. The C57BL/6J mice were randomly divided into the control (CON) group and the experimental group, which was firstly fed a HF diet for 8 weeks. Then, the HF group was subdivided into four groups and was given TS orally (including two doses) or rosiglitazone (Rosi) or vehicle for 4 weeks. Blood, skeletal muscle, and tissues were examined by measuring glycaemia and dyslipidemia-associated events. TS effectively prevented HF diet-induced increases in the levels of blood glucose, triglyceride, insulin, leptin, and free fatty acid (FFA) and weights of visceral fa; moreover, adipocytes in the visceral depots showed a reduction in size. TS treatment significantly increased the protein contents of glucose transporter 4 (GLUT4) in skeletal muscle; TS also significantly enhanced Akt phosphorylation in liver, whereas it reduced the expressions of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Moreover, TS enhanced phosphorylation of AMP-activated protein kinase (phospho-AMPK) both in skeletal muscle and liver tissue. Therefore, it is possible that the activation of AMPK by TS resulted in enhanced glucose uptake in skeletal muscle, contrasting with diminished gluconeogenesis in liver. TS exhibits hypolipidemic effect by decreasing the expressions of fatty acid synthase (FAS). Thus, antidiabetic properties of TS occurred as a result of decreased hepatic glucose production by PEPCK and G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic state by TS in HF-fed mice occurred by regulation of GLUT4, G6Pase, and FAS and phosphorylation of AMPK. PMID:25140189

  3. Measuring the orientation of taurine in the active site of the non-heme Fe(II)/α-ketoglutarate-dependent taurine hydroxylase (TauD) using electron spin echo envelope modulation (ESEEM) spectroscopy.

    PubMed

    Casey, Thomas M; Grzyska, Piotr K; Hausinger, Robert P; McCracken, John

    2013-09-12

    The position and orientation of taurine near the non-heme Fe(II) center of the α-ketoglutarate (α-KG)-dependent taurine hydroxylase (TauD) was measured using Electron Spin Echo Envelope Modulation (ESEEM) spectroscopy. TauD solutions containing Fe(II), α-KG, and natural abundance taurine or specifically deuterated taurine were prepared anaerobically and treated with nitric oxide (NO) to make an S = 3/2 {FeNO}(7) complex that is suitable for robust analysis with EPR spectroscopy. Using ratios of ESEEM spectra collected for TauD samples having natural abundance taurine or deuterated taurine, (1)H and (14)N modulations were filtered out of the spectra and interactions with specific deuterons on taurine could be studied separately. The Hamiltonian parameters used to calculate the amplitudes and line shapes of frequency spectra containing isolated deuterium ESEEM were obtained with global optimization algorithms. Additional statistical analysis was performed to validate the interpretation of the optimized parameters. The strongest (2)H hyperfine coupling was to a deuteron on the C1 position of taurine and was characterized by an effective dipolar distance of 3.90 ± 0.25 Å from the {FeNO}(7) paramagnetic center. The principal axes of this C1-(2)H hyperfine coupling and nuclear quadrupole interaction tensors were found to make angles of 26 ± 5 and 52 ± 17°, respectively, with the principal axis of the {FeNO}(7) zero-field splitting tensor. These results are discussed within the context of the orientation of substrate taurine prior to the initiation of hydrogen abstraction. PMID:23937570

  4. Hepatic Encephalopathy

    PubMed Central

    Bleibel, Wissam; Al-Osaimi, Abdullah M. S.

    2012-01-01

    Chronic liver disease and cirrhosis affect hundreds of millions of patients all over the world. The majority of patients with cirrhosis will eventually develop complications related to portal hypertension. One of these recurrent and difficult to treat complications is hepatic encephalopathy. Studies have indicated that overt hepatic encephalopathy affects 30 to 45% of patients with cirrhosis and a higher percentage may be affected by minimal degree of encephalopathy. All of these factors add to the impact of hepatic encephalopathy on the healthcare system and presents a major challenge to the gastroenterologist, hospitalist and primary care physician. PMID:23006457

  5. Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease

    PubMed Central

    Kim, Hye Yun; Kim, Hyunjin V.; Yoon, Jin H.; Kang, Bo Ram; Cho, Soo Min; Lee, Sejin; Kim, Ji Yoon; Kim, Joo Won; Cho, Yakdol; Woo, Jiwan; Kim, YoungSoo

    2014-01-01

    Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages. PMID:25502280

  6. Hepatitis B

    MedlinePlus

    ... and Change Plan Wallet card for patients to record their alcohol use over a 4-week period as a way to monitor and reduce their drinking behavior. Glossary Definitions of terms commonly used with viral hepatitis and ...

  7. Hepatitis B

    MedlinePlus

    ... U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2014;161(1):58-66. PMID 24863637 ... Development Conference Statement: Management of hepatitis B. Ann Intern Med . 2009;150:104-10. PMID: 19124811 www. ...

  8. J-Modulation in ID NMR 1H Spectrum of Taurine and Aspartate Using Spin-Echo Technique

    NASA Astrophysics Data System (ADS)

    Oturak, Halil; Sağlam, Adnan; Bahçeli, Semiha

    1999-05-01

    This study reports on a theoretical calculation of Hahn's spin-echo experiment in case of a model A2B2 spin system with a strongly coupling character and gives the experimental results of one-dimension 1H high-resolution NMR spectra of taurine and aspartate. The calculated amplitudes of the spin-echoes for two different proton groups of taurine are given. Using results of our calculations for taurine, the computer simulations of J-modulation are implemented. It is shown that the agreement be-tween the experimental and simulated spectra is good.

  9. THIN-LAYER SEPARATION OF CITRIC ACID CYCLE INTERMEDIATES, LACTIC ACID, AND THE AMINO ACID TAURINE

    EPA Science Inventory

    This paper describes a two-dimensional mixed-layer method for separating citric acid cycle intermediates, lactic acid and the amino acid taurine. The method cleanly separates all citric acid cycle intermediates tested, excepting citric acid and isocitric acid. The solvents are in...

  10. Significance of the taurine-glycine ratio as an indicator of stress

    SciTech Connect

    Scholz, N.

    1987-01-01

    For the quantification of stress effects, several methods and systems have been developed. Among others, biochemical techniques seem to be very promising. The following paper deals with the applicability of the taurine-glycine ratio as a biochemical stress index. The effects of heavy metals (Cd, Cu) as well as starvation have been investigated in the blue mussel, Mytilus edulis.

  11. Taurine Rescues Cisplatin-Induced Muscle Atrophy In Vitro: A Morphological Study

    PubMed Central

    Stacchiotti, Alessandra; Rovetta, Francesca; Ferroni, Matteo; Corsetti, Giovanni; Lavazza, Antonio; Sberveglieri, Giorgio; Aleo, Maria Francesca

    2014-01-01

    Cisplatin (CisPt) is a widely used chemotherapeutic drug whose side effects include muscle weakness and cachexia. Here we analysed CisPt-induced atrophy in C2C12 myotubes by a multidisciplinary morphological approach, focusing on the onset and progression of autophagy, a protective cellular process that, when excessively activated, may trigger protein hypercatabolism and atrophy in skeletal muscle. To visualize autophagy we used confocal and transmission electron microscopy at different times of treatment and doses of CisPt. Moreover we evaluated the effects of taurine, a cytoprotective beta-amino acid able to counteract oxidative stress, apoptosis, and endoplasmic reticulum stress in different tissues and organs. Our microscopic results indicate that autophagy occurs very early in 50 μM CisPt challenged myotubes (4 h–8 h) before overt atrophy but it persists even at 24 h, when several autophagic vesicles, damaged mitochondria, and sarcoplasmic blebbings engulf the sarcoplasm. Differently, 25 mM taurine pretreatment rescues the majority of myotubes size upon 50 μM CisPt at 24 h. Taurine appears to counteract atrophy by restoring regular microtubular apparatus and mitochondria and reducing the overload and the localization of autophagolysosomes. Such a promising taurine action in preventing atrophy needs further molecular and biochemical studies to best define its impact on muscle homeostasis and the maintenance of an adequate skeletal mass in vivo. PMID:24955211

  12. The effect of taurine on mesenteric blood flow and organ injury in sepsis.

    PubMed

    Erdem, A; Sevgili, A M; Akbiyik, F; Atilla, P; Cakar, N; Balkanci, Z D; Iskit, A B; Guc, M O

    2008-08-01

    Endotoxin decreases mesenteric blood flow and inflicts organ injury via free radicals. We investigated whether taurine, an endogenous antioxidant and vasodilator, could attenuate the deleterious effects of endotoxin in a mouse model of sepsis. Swiss albino mice were allocated into four groups and treated either with taurine (150 mg/kg, i.p. at 0(th), 8(th), 16(th) h) or its solvent sterile saline (NaCl 0.9%, w/v) while E. coli endotoxin (20 mg/kg, i.p.) or its solvent saline were also given at 8(th) h. At 24(th) h the animals were anaesthetized and the mesenteric blood flow was measured by using perivascular ultrasonic Doppler-flowmeter. The animals were then exsanguinated, the spleen, liver, and kidneys were isolated for histopathological examination. Thiobarbituric acid-reacting substances (TBARS), glutathione, and myeloperoxidase activity were determined in the liver samples. Endotoxin significantly decreased the mesenteric blood flow and glutathione levels in liver while TBARS and myeloperoxidase activity were increased. However, taurine did not block the deleterious effects of endotoxin nor it did attenuate the histopathological injury. Therefore, we concluded that endotoxin-induced organ injury via free radicals is resistant to blockade by taurine. PMID:18163178

  13. SUPPLEMENTATION OF TAURINE AND METHIONINE TO ALL-PLANT PROTEIN DIETS FOR RAINBOW TROUT (OMCORHYNCHUS MYKISS).

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Current trends in trout production include decreasing levels of fishmeal content in feeds for faster growing strains of fish; therefore, taurine may be a limiting nutrient in support of elevated growth for strains of genetically-improved rainbow trout. A 12-week feeding trial was conducted using a f...

  14. SUPPLEMENTATION OF TAURINE AND METHIONINE TO ALL-PLANT PROTEIN DIETS FOR RAINBOW TROUT (ONCORHYNCHUS MYKISS).

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Current trends in trout production include decreasing levels of fishmeal content in feeds for faster growing strains of fish; therefore, taurine may be a limiting nutrient in support of elevated growth for strains of genetically-improved rainbow trout. A 12-week feeding trial was conducted using a f...

  15. Transportation.

    ERIC Educational Resources Information Center

    Crank, Ron

    This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with transportation and energy use. Its objective is for the student to be able to discuss the implication of energy usage as it applies to the area of transportation. Some topics covered are efficiencies of various transportation…

  16. Hepatitis B Foundation

    MedlinePlus

    ... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 10 Other Languages . Resource Video See ...

  17. Hepatitis C - children

    MedlinePlus

    ... virus (HCV). Other common hepatitis virus infections include hepatitis A and hepatitis B . ... Elisofon SA, Jonas MMF. Viral hepatitis in children. In: Boyer TD, Manns MP, Sanyal AJ, eds. Zakim & Boyer's Hepatology: A Textbook of Liver Disease. 6th ed. ...

  18. Hepatitis A FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis A FAQs for the Public Recommend on Facebook ...

  19. Delta agent (Hepatitis D)

    MedlinePlus

    Hepatitis D virus ... Hepatitis D virus (HDV) is found only in people who carry the hepatitis B virus. HDV may make liver ... B virus but who never had symptoms. Hepatitis D infects about 15 million people worldwide. It occurs ...

  20. Hepatitis C FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis C FAQs for the Public Recommend on Facebook ...

  1. Hepatitis B FAQs

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis B FAQs for the Public Recommend on Facebook ...

  2. Hepatitis A Test

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Hepatitis A Testing Share this page: Was this page ... HAV-Ab total; Anti-HAV Formal name: Viral Hepatitis A Antibody Related tests: Hepatitis B Testing ; Hepatitis ...

  3. Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

    MedlinePlus

    ... Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 Table of ... Stomach ache Nausea Diarrhea No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will ...

  4. Superoxide dismutase and taurine supplementation improves in vitro blastocyst yield from poor-quality feline oocytes.

    PubMed

    Ochota, Małgorzata; Pasieka, Anna; Niżański, Wojciech

    2016-03-15

    Blastocyst production in vitro seems to be crucial part of assisted reproduction techniques in feline species. However, the results of cats' oocyte maturation and embryo development are still lower than those in other species. The aim of this study was to evaluate whether the supplementation with superoxide dismutase (SOD) and taurine during maturation or culture would improve the blastocyst yield obtained from lower grades of oocytes, that are usually discarded, as not suitable for further in vitro purposes. To investigate the effect of antioxidants' addition, the good- and poor-quality oocytes, were cultured with the addition of 10-mmol taurine and 600 UI/mL SOD. The nuclear maturity, embryo development, and blastocyst quality were subsequently assessed. In control group, without antioxidant supplementation, significantly less poor-quality oocytes matured (42% vs. 62%) and more degenerated (35% vs. 20%), comparing to the experimental group supplemented with SOD and taurine. The amount of obtained blastocyst was much higher, when poor quality oocytes were supplemented with SOD and taurine (supplementation to IVM-4%; supplementation to IVC-5.5%; supplementation to IVM and IVC-5.9% of blastocyst), comparing to not supplemented control group (1.3%). The best blastocysts were obtained when poor oocytes had antioxidants added only during embryo culture (185 ± 13.4 blastomeres vs. 100 ± 1.5 in control). In the present study, we reported that the lower grades of oocytes can better mature and form significantly more blastocysts with better quality, when cultured with addition of SOD and taurine. PMID:26643604

  5. Hepatitis C: Sex and Sexuality

    MedlinePlus

    ... with Hepatitis » Sex and Sexuality: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... hepatitis C virus through sex. Can you pass hepatitis C to a sex partner? Yes, but it ...

  6. Investigation on the adsorption characteristics of sodium benzoate and taurine on gold nanoparticle film by ATR-FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Kumar, Naveen; Thomas, S.; Tokas, R. B.; Kshirsagar, R. J.

    2014-01-01

    Fourier transform infrared (FTIR) spectroscopic studies of sodium benzoate and taurine adsorbed on gold nanoparticle (AuNp) film on silanised glass slides have been studied by attenuated total reflection technique (ATR). The surface morphology of the AuNp films has been measured by Atomic Force Microscopy. The ATR spectra of sodium benzoate and taurine deposited on AuNp film are compared with ATR spectra of their powdered bulk samples. A new red-shifted band appeared along with the symmetric and asymmetric stretches of carboxylate group of sodium benzoate leading to a broadening of the above peaks. Similar behavior is also seen in the case of symmetric and asymmetric stretches of sulphonate group of taurine. The results indicate presence of both chemisorbed and physisorbed layers of both sodium benzoate and taurine on the AuNp film with bottom layer chemically bound to AuNp through carboxylate and sulphonate groups respectively.

  7. Hepatitis C

    PubMed Central

    Mehta, Bharti; Kumar Dharma, Vijay; Chawla, Sumit; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Hepatitis C Virus (HCV) infection is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following acute infection, 20% of people eliminate the virus over weeks or months and are often asymptomatic. The remaining 80% of people will develop chronic disease, of which approximately 20% will eventually develop liver cirrhosis and 1–5% will develop liver cancer. About 150 million people are chronically infected with HCV, and more than 350 000 people die every year from hepatitis C related liver diseases. The economic cost of hepatitis C is significant both to the individual and to the society. In the United States the average lifetime cost of the disease was estimated at $33 407 USD with the cost of a liver transplant approximately $200 000 USD. PEG-IFN and ribavirin treatment is also expensive and, at an average cost of approximately GB £7000 in the UK for a treatment course, is unaffordable in developing countries. Hepatitis C, not only brings down the quality of the life of individuals but also affect progress of the nation by adding financial burden. If we prevent the disease from occurring or find a perfect cure of the disease, in form of a prophylactic or therapeutic vaccine, it will be a boon to not only to the individual but to the nation as a whole. PMID:24165512

  8. Taurine activates excitatory non-synaptic glycine receptors on dopamine neurones in ventral tegmental area of young rats

    PubMed Central

    Wang, Fushun; Xiao, Cheng; Ye, Jiang Hong

    2005-01-01

    The physiological and pharmacological properties of taurine-induced responses were investigated in dopaminergic (DA) neurones from the ventral tegmental area (VTA) of young rats aged 1–13 postnatal days, either in acute brain slices or acutely dissociated neurones. When whole-cell responses were recorded from current-clamped neurones using the gramicidin-perforated technique, the application of taurine (0.01–30 mm) accelerated firings and induced membrane depolarization. In voltage-clamped neurones, taurine induced a current which was antagonized by strychnine and by picrotoxin, but not by bicuculline. In addition, taurine-induced current showed complete cross-desensitization with glycine-activated currents but not with γ-aminobutyric acid (GABA)-activated currents. Thus, taurine is a full agonist of the glycine receptors (GlyRs) in the VTA. Further studies found that taurine acted mainly on non-synaptic GlyRs. The application of 20 μm bicuculline abolished the spontaneous inhibitory post-synaptic currents (IPSCs) in 40/45 neurones, and 93% of the evoked IPSCs. The addition of 1 μm strychnine completely eliminated the remaining IPSCs. These results suggest that GABAergic IPSCs predominate, and that functional glycinergic synapses are present in a subset of the VTA neurones. The application of 1 μm strychnine alone induced an outward current, suggesting that these neurones were exposed to tonically released taurine/glycine. In conclusion, by activating non-synaptic GlyRs, taurine may act as an excitatory extra-synaptic neurotransmitter in the VTA during early development. PMID:15817633

  9. Influence of chronic administration of anabolic androgenic steroids and taurine on haemostasis profile in rats: a thrombelastographic study.

    PubMed

    Roşca, Adrian E; Badiu, Corin; Uscătescu, Valentina; Stoian, Irina; Mirică, Radu; Braga, Radu I; Pavel, Bogdan; Zăgrean, Leon

    2013-04-01

    Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone with thrombogenic potential in high doses and long-term administration. Taurine, a widely distributed amino-sulfonic acid, is known for its beneficial effects in hypercoagulable states. In order to assess the impact of chronic administration of high doses of AAS and taurine upon haemostasis process in rats, 40 male Wistar rats were divided into four equal groups: control group (group C) - no treatment; androgen group (group A) - received 10 mg/kg per week of nandrolone decanoate (DECA); taurine (group T) - received oral supplementation of 2% taurine in drinking water; androgen and taurine group (group AT) - concomitant administration of DECA and taurine. After 12 weeks, blood samples were collected and haemostasis parameters were assessed with the thrombelastographic (TEG) analysis system: reaction time, clot kinetics (K, α), final clot strength, coagulation index and the clot lysis (Ly30). Nandrolone significantly decreased reaction time in group A compared with control (P<0.001), whereas taurine significantly increase reaction time (P=0.01), and this effect was maintained in group AT compared with group A (P=0.009). Similar differences between groups have been recorded for the clot kinetics parameters K, α. The final clot strength and coagulation index were significantly increased in group A versus group C (P=0.04, respectively P<0.001), but not in group AT versus group C (P>0.05). There were no differences in clot lysis, as shown by Ly30. Nandrolone produces an accelerated clot development and an increased clot firmness in Wistar rats. Taurine association ensures a protective effect against this hypercoagulable state, partially restoring the altered parameters of the coagulation profile. PMID:23160242

  10. Therapeutic effect of taurine against aluminum-induced impairment on learning, memory and brain neurotransmitters in rats.

    PubMed

    Wenting, Lu; Ping, Liu; Haitao, Jiao; Meng, Qiao; Xiaofei, Ren

    2014-10-01

    The aim of the study was to demonstrate the therapeutic effect of taurine against aluminum (Al)-induced neurological disorders in rats. Forty-two Wistar rats were randomly allotted into six groups: control (saline only), Al exposure (281.4 mg/kg/day for 1 month), Al + taurine (Al administration as previously plus taurine, doses were 200, 400 and 800 mg/kg/day, respectively, for the next 1 month) and prevention group (along with the Al administration as previously, 400 mg/kg/day taurine was treated for 1 month. During the next 1 month, rats were given taurine 400 mg/kg/day only). Starting from the sixth week, the body weight gain was significantly reduced in Al exposure group compared with saline (P < 0.05), and at the eighth week, the gain in prevention group was increased compared with Al (P < 0.05). Brain coefficient was gained in Al exposure compared with saline or prevention group (P < 0.05). Al exposure resulted in learning and memory impairment by increasing the escape latency and searching distance, meanwhile, decreasing the swimming time in the quadrant of platform and the numbers of crossing the platform (P < 0.05). Unsurprisingly, taurine treatment (400, 800 mg/kg/day and prevention) significantly protected against Al-induced brain dysfunction (P < 0.05). The Al exposure led to significant decreases in levels of γ-GABA and Tau, meanwhile, increased in level of Asp and Glu compared with saline (P < 0.05). And yet, taurine treatment partially reversed the deteriorated changes. The results suggested that taurine probably has neuroprotective effect against Al-induced learning, memory and brain neurotransmitters dysfunction. PMID:24770980

  11. Taurine Supplementation Reduces Blood Pressure and Prevents Endothelial Dysfunction and Oxidative Stress in Post-Weaning Protein-Restricted Rats

    PubMed Central

    Maia, Aline R.; Batista, Thiago M.; Victorio, Jamaira A.; Clerici, Stefano P.; Delbin, Maria A.; Carneiro, Everardo M.; Davel, Ana P.

    2014-01-01

    Introduction Taurine is a sulfur-containing amino acid that exerts protective effects on vascular function and structure in several models of cardiovascular diseases through its antioxidant and anti-inflammatory properties. Early protein malnutrition reprograms the cardiovascular system and is linked to hypertension in adulthood. This study assessed the effects of taurine supplementation in vascular alterations induced by protein restriction in post-weaning rats. Methods and Results Weaned male Wistar rats were fed normal- (12%, NP) or low-protein (6%, LP) diets for 90 days. Half of the NP and LP rats concomitantly received 2.5% taurine supplementation in the drinking water (NPT and LPT, respectively). LP rats showed elevated systolic, diastolic and mean arterial blood pressure versus NP rats; taurine supplementation partially prevented this increase. There was a reduced relaxation response to acetylcholine in isolated thoracic aortic rings from the LP group that was reversed by superoxide dismutase (SOD) or apocynin incubation. Protein expression of p47phox NADPH oxidase subunit was enhanced, whereas extracellular (EC)-SOD and endothelial nitric oxide synthase phosphorylation at Ser 1177 (p-eNOS) were reduced in aortas from LP rats. Furthermore, ROS production was enhanced while acetylcholine-induced NO release was reduced in aortas from the LP group. Taurine supplementation improved the relaxation response to acetylcholine and eNOS-derived NO production, increased EC-SOD and p-eNOS protein expression, as well as reduced ROS generation and p47phox expression in the aortas from LPT rats. LP rats showed an increased aortic wall/lumen ratio and taurine prevented this remodeling through a reduction in wall media thickness. Conclusion Our data indicate a protective role of taurine supplementation on the high blood pressure, endothelial dysfunction and vascular remodeling induced by post-weaning protein restriction. The beneficial vascular effect of taurine was

  12. Dietary taurine and nutrients intake and anthropometric and body composition data by abdominal obesity in Korean male college students.

    PubMed

    Sung, Min Jung; Chang, Kyung Ja

    2009-01-01

    The purpose of this study was to investigate the relationship between abdominal obesity and dietary taurine intake, nutrient intake, anthropometric data and body composition in Korean male college students. One hundred seventy four subjects were divided into 2 groups based on abdominal obesity as estimated by waist circumference (cm) (Lee et al. 2006): normal group (waist circumference (cm): < 90 cm, n = 141), obese group (waist circumference (cm): > or = 90 cm, n = 33). A three day-recall method was used to assess diet (2 weekdays and 1 weekend). Anthropometric data and body composition were measured with Inbody 3.0 (Bioelectrical Impedance Fatness Analyzer). Average dietary intake of taurine in the normal and obese groups was 123.1 +/- 78.8 mg/day and 128.4 +/- 79.6 mg/day, respectively. There was no significant difference in dietary taurine and nutrient intake between the normal and obese groups. However, data of anthropometric measurements and body composition in the obese group were significantly elevated compared to those of the normal group. In the normal group, dietary taurine intake was positively correlated with nutrient intake (p < 0.01), the exception being the intake of plant lipid and of animal calcium. In the obese group, dietary taurine intake was positively correlated with the intake of energy foods and of animal lipid (p < 0.05). There were positive correlations between dietary taurine intake, weight and hip circumference (p < 0.05) in the normal group. However, there was no significant correlation between dietary taurine intake and anthropometric and body composition data in the obese group. Therefore, the data suggest that further study is warranted to examine the relationship between dietary taurine intake and abdominal obesity. PMID:19239175

  13. Hepatic encephalopathy.

    PubMed

    Córdoba, Juan; Mínguez, Beatriz

    2008-02-01

    Hepatic encephalopathy is a severe complication of cirrhosis that is related to the effects of ammonia. Analysis of interorgan ammonia trafficking has identified an important role of skeletal muscle in ammonia removal and has highlighted the importance of the nutritional status. Ammonia causes neurotransmitter abnormalities and induces injury to astrocytes that is partially mediated by oxidative stress. These disturbances lead to astrocyte swelling and brain edema, which appear to be involved in the pathogenesis of neurological manifestations. Inflammatory mediators worsen brain disturbances. New methods for assessing hepatic encephalopathy include clinical scales, neuropsychological tests, imaging of portal-systemic circulation, and magnetic resonance of the brain. Reappraisal of current therapy indicates the need for performing placebo-controlled trials and the lack of evidence for administering diets with restricted protein content. Liver transplant should be considered in selected patients with hepatic encephalopathy. Future prospects include new drugs that decrease plasma ammonia, measures to reduce brain edema, and liver-support devices. PMID:18293278

  14. [Hepatic encephalopathy].

    PubMed

    Córdoba, Juan; Mur, Rafael Esteban

    2014-07-01

    Hepatic encephalopathy (EH) is a severe complication of hepatic cirrhosis that is characterized by multiple neuropsychiatric manifestations. EH is usually triggered by a precipitating factor and occurs in patients with severely impaired hepatic function. Minimal EH is characterized by minor cognitive impairments that are difficult to specify but represent a risk for the patients. The primary pathophysiological mechanism of EH is considered to be an increase in blood ammonia with an impairment in the patency of the blood-brainbarrier and its metabolism to glutamine in astrocytes. The diagnosis is clinical and neuroimaging techniques can be complementary. The diagnosis of minimal EH requires specific neurocognitive tests. The clinical evaluation should be directed towards identifying the trigger. Nonabsorbable disaccharides and rifaximin constitute the treatment of choice, along with prophylaxis for new episodes. PMID:25087716

  15. Protective effects of taurine against alloxan-induced diabetic cataracts and refraction changes in New Zealand White rabbits.

    PubMed

    Hsu, Yu-Wen; Yeh, Shang-Min; Chen, Ya-Yu; Chen, Yi-Chen; Lin, Shiun-Long; Tseng, Jung-Kai

    2012-10-01

    The present study examined the protective effects of taurine on alloxan-induced diabetic cataracts and lens damage in male New Zealand White rabbits. The animals were randomly divided into three treatment groups: (1) normal control (vehicle administration); (2) diabetes (100 mg/kg alloxan administration); and (3) diabetes + taurine (1% [w/v] taurine dissolved in drinking water and alloxan administration). The results showed that alloxan-induced diabetes caused significant (p < 0.05) hyperglycemia, hyperopic refraction shifts, cataract formation and lens damage compared with the normal control group. In contrast, the administration of taurine for 24 weeks significantly ameliorated the alloxan-induced elevated levels of blood glucose, level of hyperopic refraction error shifts in the eyes and progression of diabetic cataract formation in the lens in rabbits. Moreover, histopathology showed that the taurine supplement reduced the incidence of lens lesions induced by hyperglycemia. Overall, the studies demonstrate that taurine exhibits potent protective effects against alloxan-induced diabetic cataracts and refraction changes in rabbits. PMID:22940558

  16. Acute effects of taurine on sarcoplasmic reticulum Ca2+ accumulation and contractility in human type I and type II skeletal muscle fibers.

    PubMed

    Dutka, T L; Lamboley, C R; Murphy, R M; Lamb, G D

    2014-10-01

    Taurine occurs in high concentrations in muscle and is implicated in numerous physiological processes, yet its effects on many aspects of contractility remain unclear. Using mechanically skinned segments of human vastus lateralis muscle fibers, we characterized the effects of taurine on sarcoplasmic reticulum (SR) Ca2+ accumulation and contractile apparatus properties in type I and type II fibers. Prolonged myoplasmic exposure (>10 min) to taurine substantially increased the rate of accumulation of Ca2+ by the SR in both fiber types, with no change in the maximum amount accumulated; no such effect was found with carnosine. SR Ca2+ accumulation was similar with 10 or 20 mM taurine, but was significantly slower at 5 mM taurine. Cytoplasmic taurine (20 mM) had no detectable effects on the responsiveness of the Ca2+ release channels in either fiber type. Taurine caused a small increase in Ca2+ sensitivity of the contractile apparatus in type I fibers, but type II fibers were unaffected; maximum Ca(2+)-activated force was unchanged in both cases. The effects of taurine on SR Ca2+ accumulation (1) only became apparent after prolonged cytoplasmic exposure, and (2) persisted for some minutes after complete removal of taurine from the cytoplasm, consistent with the hypothesis that the effects were due to an action of taurine from inside the SR. In summary, taurine potentiates the rate of SR Ca2+ uptake in both type I and type II human fibers, possibly via an action from within the SR lumen, with the degree of potentiation being significantly reduced at low physiological taurine levels. PMID:25123198

  17. More Power to OATP1B1: An Evaluation of Sample Size in Pharmacogenetic Studies Using a Rosuvastatin PBPK Model for Intestinal, Hepatic, and Renal Transporter-Mediated Clearances.

    PubMed

    Emami Riedmaier, Ariane; Burt, Howard; Abduljalil, Khaled; Neuhoff, Sibylle

    2016-07-01

    Rosuvastatin is a substrate of choice in clinical studies of organic anion-transporting polypeptide (OATP)1B1- and OATP1B3-associated drug interactions; thus, understanding the effect of OATP1B1 polymorphisms on the pharmacokinetics of rosuvastatin is crucial. Here, physiologically based pharmacokinetic (PBPK) modeling was coupled with a power calculation algorithm to evaluate the influence of sample size on the ability to detect an effect (80% power) of OATP1B1 phenotype on pharmacokinetics of rosuvastatin. Intestinal, hepatic, and renal transporters were mechanistically incorporated into a rosuvastatin PBPK model using permeability-limited models for intestine, liver, and kidney, respectively, nested within a full PBPK model. Simulated plasma rosuvastatin concentrations in healthy volunteers were in agreement with previously reported clinical data. Power calculations were used to determine the influence of sample size on study power while accounting for OATP1B1 haplotype frequency and abundance in addition to its correlation with OATP1B3 abundance. It was determined that 10 poor-transporter and 45 intermediate-transporter individuals are required to achieve 80% power to discriminate the AUC0-48h of rosuvastatin from that of the extensive-transporter phenotype. This number was reduced to 7 poor-transporter and 40 intermediate-transporter individuals when the reported correlation between OATP1B1 and 1B3 abundance was taken into account. The current study represents the first example in which PBPK modeling in conjunction with power analysis has been used to investigate sample size in clinical studies of OATP1B1 polymorphisms. This approach highlights the influence of interindividual variability and correlation of transporter abundance on study power and should allow more informed decision making in pharmacogenomic study design. PMID:27385171

  18. Hepatitis A

    MedlinePlus

    ... Low-grade fever Nausea and vomiting Pale or clay-colored stools Yellow skin (jaundice) ... The virus does not remain in the body after the infection is gone. Most people with hepatitis A recover within 3 months. Nearly all people get better within 6 months. There ...

  19. Autoimmune Hepatitis

    MedlinePlus

    ... provider will closely monitor and manage any side effects that may occur, as high doses of prednisone are often prescribed to treat autoimmune hepatitis. Immune system suppressors. Medications that suppress the immune system prevent the body from making autoantibodies and block the immune reaction ...

  20. Hepatitis A

    MedlinePlus

    ... Advisory Board Sponsors Sponsorship Opporunities Spread the Word Shop AAP Find a Pediatrician ... Body Hepatitis means “inflammation of the liver.” This inflammation can be caused by a wide variety of toxins, drugs, and metabolic diseases, as well as infection. There ...

  1. Potential role of curcumin and taurine combination therapy on human myeloid leukemic cells propagated in vitro.

    PubMed

    El-Houseini, Motawa E; Refaei, Mohammed Osman; Amin, Ahmed Ibrahim; Abol-Ftouh, Mahmoud A

    2013-10-01

    Curcumin and taurine are natural products that have been used in this study evaluating their therapeutic effect on myeloid leukemic cells propagated in vitro. Sixty patients with myeloid leukemia and 30 healthy volunteers were enrolled in the study. All patient groups were admitted to the Medical Oncology Department of the National Cancer Institute, Cairo University. There were statistically significant differences between treated leukemic cells compared to normal mononuclear leukocytes in cell density, interferon-γ and immunophenotypic profile, mainly CD4+, CD8 + and CD25+. This work highlights the possibility of using curcumin and taurine as a potential useful therapy in the management of patients suffering from chronic and acute myeloid leukemias. PMID:23418874

  2. Human mitochondrial diseases caused by lack of taurine modification in mitochondrial tRNAs.

    PubMed

    Suzuki, Tsutomu; Nagao, Asuteka; Suzuki, Takeo

    2011-01-01

    Mitochondrial DNA mutations that cause mitochondrial dysfunction are responsible for a wide spectrum of human diseases, referred to as mitochondrial diseases. Pathogenic point mutations are found frequently in genes encoding mitochondrial (mt) tRNAs, indicating that impaired functioning of mutant mt tRNAs is the primary cause of mitochondrial dysfunction. Our previous studies revealed the absence of posttranscriptional taurine modification at the anticodon wobble uridine in mutant mt tRNAs isolated from cells derived from patients with two major classes of mitochondrial diseases, MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and MERRF (myoclonus epilepsy associated with ragged red fibers). Defective taurine modification of the mutant mt tRNAs results in a deficiency in protein synthesis as the cognate codons of the mutant mt tRNA cannot be decoded. These findings represent the first evidence of a molecular pathogenesis caused by an RNA modification disorder. PMID:21957023

  3. Taurine for the Treatment of Canine Dilated Cardiomyopathy: A Veterinarian's Personal Experience.

    PubMed

    Vail, Jane

    2006-01-01

    In dogs, dilated cardiomyopathy is a common cardiac disease that is associated with treatment failure, a progressively compromised quality of life, and eventual death from heart failure. Cardiomyopathy in companion animals is treated with a variety of drugs manufactured for the management of cardiac dyfunction in humans, but often those agents do not produce a significantly beneficial response in veterinary patients. In this article, Lara Ivan, DVM, presents her personal experience with the use of a compounded form of the amino acid taurine in the treatment of her Doberman pinscher, whose dilated cardiomyopathy was characteristically sudden in onset. Robert Borger, RPh, a specialist in veterinary compounding, comments on the preparation of taurine for use in dogs with dilated cardiomyopathy. PMID:23974413

  4. Plasma amino-acids in hereditary retinal disease. Ornithine, lysine, and taurine.

    PubMed Central

    Berson, E. L.; Schmidt, S. Y.; Rabin, A. R.

    1976-01-01

    Plasma free amino-acids were measured in 41 patients with hereditary chorio-retinal degenerations including 26 with retinitis pigmentosa and five with gyrate atrophy of the choroid, six relatives of patients with gyrate atrophy, and 13 normal subjects. Patients with gyrate atrophy had very increased levels of ornithine and slightly decreased mean lysine values. Most relatives had slightly increased ornithine. Taurine, known to be deficient in the plasma of casein-fed cats with photoreceptor degeneration, was normal in all patients. Amino-acid precursors and metabolites of ornithine and taurine were also normal in the plasma. Although the association of high ornithine and gyrate atrophy appears constant, high levels of ornithine alone do not necessarily lead to this degeneration; one patient with known hyperammonaemia, homocitrullinuria and a tenfold increase in plasma ornithine was found to have a normal fundus appearance and normal electroretinogram. PMID:1268174

  5. Synthesis of taurine-fluorescein conjugate and evaluation of its retina-targeted efficiency in vitro.

    PubMed

    Huang, Meihong; Song, Jiaqi; Lu, Bingzheng; Huang, Huizhi; Chen, Yizhen; Yin, Wei; Zhu, Wenbo; Su, Xinwen; Wu, Chuanbin; Hu, Haiyan

    2014-12-01

    In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F-Tau conjugate. Nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) were used to confirm the successful synthesis of F-Tau. The cellular uptake of F-Tau in adult retinal pigment epithelial cells (ARPE-19) and human retinal microvascular endothelial cells (hRMECs) was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of logP of F-Tau compared with fluorescein. As compared with fluorescein, F-Tau showed little toxicity, and was retained longer by cells in uptake experiments. F-Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells (P<0.05). These results showed that taurine may be a useful ligand for targeting small-molecule hydrophobic pharmaceuticals into the retina. PMID:26579416

  6. The anion-transfer system of erythrocyte membranes. N-(7-Nitrobenzofurazan-4-yl)taurine, a fluorescent substrate-analogue of the system.

    PubMed Central

    Eidelman, O; Zangvill, M; Razin, M; Ginsburg, H; Cabantchik, Z I

    1981-01-01

    The fluorescent probe Nbd-Tau [N-(7-nitrobenzofurazan-4-yl)taurine] was synthesized and evaluated as a potential substrate of the anion-transport system of human erythrocyte membrane. The probe inhibited Cl- exchange in a competitive manner from either surface of the membrane, displaying Ki values in the mM range at the inner surface and in the microM range at the outer surface. Inhibition from within cells was via interaction with Cl--transport sites, whereas from it was via interaction with sites of unidentified nature. Nbd-Tau efflux from cells was monitored fluorimetrically in a continuous mode by a novel method that circumvents separation of the cells from the medium. Using this method, it is shown that Nbd-Tau efflux fulfils the following criteria of a substrate of the anion transport system: (a) susceptibility to classical and specific inhibitors of the system; (b) competitive inhibition with Cl- for anion-transport sites; and (c) temperature coefficient comparable with that of Cl- exchange. The fluorometric method is highly sensitive, versatile, and kinetically informative. With minor modifications it can be used for measuring anion transport across "ghost" and isolated membrane vesicles. PMID:7316966

  7. Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats.

    PubMed

    Roşca, A E; Stoian, I; Badiu, C; Gaman, L; Popescu, B O; Iosif, L; Mirica, R; Tivig, I C; Stancu, C S; Căruntu, C; Voiculescu, S E; Zăgrean, L

    2016-01-01

    Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme. PMID:27254659

  8. Taurine is absent from amino components in fruits of Opuntia ficus-indica.

    PubMed

    Ali, Hatem Salama Mohamed; Al-Khalifa, Abdulrahman Saleh; Brückner, Hans

    2014-01-01

    Juices of edible fruits from Opuntia ficus-indica (L.) Miller, commonly named prickly pears or Indian figs, were analysed for amino acids using an automated amino acid analyser run in the high-resolution physiological mode. Emphasis was put on the detection of free taurine (Tau), but Tau could be detected neither in different cultivars of prickly pears from Italy, South Africa and the Near East nor in commercially available prickly pear juices from the market. PMID:25485199

  9. The Multifaceted Origin of Taurine Cattle Reflected by the Mitochondrial Genome

    PubMed Central

    Olivieri, Anna; Malusà, Arianna; Pala, Maria; Kashani, Baharak Hooshiar; Perego, Ugo A.; Ajmone-Marsan, Paolo; Liotta, Luigi; Semino, Ornella; Bandelt, Hans-Jürgen; Ferretti, Luca; Torroni, Antonio

    2009-01-01

    A Neolithic domestication of taurine cattle in the Fertile Crescent from local aurochsen (Bos primigenius) is generally accepted, but a genetic contribution from European aurochsen has been proposed. Here we performed a survey of a large number of taurine cattle mitochondrial DNA (mtDNA) control regions from numerous European breeds confirming the overall clustering within haplogroups (T1, T2 and T3) of Near Eastern ancestry, but also identifying eight mtDNAs (1.3%) that did not fit in haplogroup T. Sequencing of the entire mitochondrial genome showed that four mtDNAs formed a novel branch (haplogroup R) which, after the deep bifurcation that gave rise to the taurine and zebuine lineages, constitutes the earliest known split in the mtDNA phylogeny of B. primigenius. The remaining four mtDNAs were members of the recently discovered haplogroup Q. Phylogeographic data indicate that R mtDNAs were derived from female European aurochsen, possibly in the Italian Peninsula, and sporadically included in domestic herds. In contrast, the available data suggest that Q mtDNAs and T subclades were involved in the same Neolithic event of domestication in the Near East. Thus, the existence of novel (and rare) taurine haplogroups highlights a multifaceted genetic legacy from distinct B. primigenius populations. Taking into account that the maternally transmitted mtDNA tends to underestimate the extent of gene flow from European aurochsen, the detection of the R mtDNAs in autochthonous breeds, some of which are endangered, identifies an unexpected reservoir of genetic variation that should be carefully preserved. PMID:19484124

  10. Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats

    PubMed Central

    Roşca, A.E.; Stoian, I.; Badiu, C.; Gaman, L.; Popescu, B.O.; Iosif, L.; Mirica, R.; Tivig, I.C.; Stancu, C.S.; Căruntu, C.; Voiculescu, S.E.; Zăgrean, L.

    2016-01-01

    Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme. PMID:27254659

  11. Persistent GABAA/C responses to gabazine, taurine and beta-alanine in rat hypoglossal motoneurons.

    PubMed

    Chesnoy-Marchais, D

    2016-08-25

    In hypoglossal motoneurons, a sustained anionic current, sensitive to a blocker of ρ-containing GABA receptors, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) and insensitive to bicuculline, was previously shown to be activated by gabazine. In order to better characterize the receptors involved, the sensitivity of this atypical response to pentobarbital (30μM), allopregnanolone (0.3μM) and midazolam (0.5μM) was first investigated. Pentobarbital potentiated the response, whereas the steroid and the benzodiazepine were ineffective. The results indicate the involvement of hybrid heteromeric receptors, including at least a GABA receptor ρ subunit and a γ subunit, accounting for the pentobarbital-sensitivity. The effects of the endogenous β amino acids, taurine and β-alanine, which are released under various pathological conditions and show neuroprotective properties, were then studied. In the presence of the glycine receptor blocker strychnine (1μM), both taurine (0.3-1mM) and β-alanine (0.3mM) activated sustained anionic currents, which were partly blocked by TPMPA (100μM). Thus, both β amino acids activated ρ-containing GABA receptors in hypoglossal motoneurons. Bicuculline (20μM) reduced responses to taurine and β-alanine, but small sustained responses persisted in the presence of both strychnine and bicuculline. Responses to β-alanine were slightly increased by allopregnanolone, indicating a contribution of the bicuculline- and neurosteroid-sensitive GABAA receptors underlying tonic inhibition in these motoneurons. Since sustained activation of anionic channels inhibits most mature principal neurons, the ρ-containing GABA receptors permanently activated by taurine and β-alanine might contribute to some of their neuroprotective properties under damaging overexcitatory situations. PMID:27246441

  12. Differential regulation of taurine biosynthesis in rainbow trout and Japanese flounder

    PubMed Central

    Wang, Xuan; He, Gen; Mai, Kangsen; Xu, Wei; Zhou, Huihui

    2016-01-01

    Animals have varied taurine biosynthesis capability, which was determined by activities of key enzymes including cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD). However, whether CDO and CSD are differentially regulated across species remains unexplored. In the present study, we examined the regulations of CDO and CSD in rainbow trout and Japanese flounder, the two fish species with high and low taurine biosynthesis ability respectively. Our results showed that the expression of CDO was lower in rainbow trout but more responsive to cysteine stimulation compared to that in Japanese flounder. On the other hand, both the expression and catalytic efficiency (kcat) of CSD were higher in rainbow trout than those of Japanese flounder. A three-residue substrate recognition motif in rainbow trout CSD with sequence of F126/S146/Y148 was identified to be responsible for high kcat, while that with sequence of F88/N108/F110 in Japanese flounder led to low kcat, as suggested by site-directed mutagenesis studies. In summary, our results determined new aspects of taurine biosynthesis regulation across species. PMID:26880478

  13. Perinatal Taurine Alters Arterial Pressure Control and Renal Function in Adult Offspring

    PubMed Central

    Roysommuti, Sanya; Lerdweeraphon, Wichaporn; Malila, Pisamai; Jirakulsomchok, Dusit; Wyss, J. Michael

    2009-01-01

    The present study investigates the effect of perinatal taurine exposure on renal function in adult, female rats on a high sugar diet. Perinatal taurine depleted (TD), supplemented (TS) or untreated control (C) female offspring were fed normal rat chow and tap water (CW,TDW or TSW) or tap water with 5% glucose (CG, TDG or TSG) after weaning. At 7–8 weeks of age, renal function was studied in the conscious, restrained rats. Mean arterial pressure was significantly higher in TDW, TDG, and TSG rats. Plasma sodium concentration was significantly lower in all glucose treated animals, but the greatest decrease was in TDW rats. Basal renal blood flow was lowest in TSW and TSG, and the responses to a saline load were also lowest in those two groups. These changes were consistent with increased renal vascular resistance. The basal glomerular filtration rate was lowest in TSW, but the responses to a saline load were similar in all of the groups. Water excretion was lower in TSG and TSW, consistent with increased renal tubular water reabsorption. These data suggest that perinatal taurine exposure alters normal renal function and renal responses to dietary sugar in adult female offspring. PMID:19239145

  14. The effect of urea and taurine as hydrophilic penetration enhancers on stratum corneum lipid models.

    PubMed

    Mueller, J; Oliveira, J S L; Barker, R; Trapp, M; Schroeter, A; Brezesinski, G; Neubert, R H H

    2016-09-01

    To optimize transdermal application of drugs, the barrier function of the skin, especially the stratum corneum (SC), needs to be reduced reversibly. For this purpose, penetration enhancers like urea or taurine are applied. Until now, it is unclear if this penetration enhancement is caused by an interaction with the SC lipid matrix or related to effects within the corneocytes. Therefore, the effects of both hydrophilic enhancers on SC models with different dimensionality, ranging from monolayers to multilayers, have been investigated in this study. Many sophisticated methods were applied to ascertain the mode of action of both substances on a molecular scale. The experiments reveal that there is no specific interaction when 10% urea or 5% taurine solutions are added to the SC model systems. No additional water uptake in the head group region and no decrease of the lipid chain packing density have been observed. Consequently, we suppose that the penetration enhancing effect of both substances might be based on the introduction of large amounts of water into the corneocytes, caused by the enormous water binding capacity of urea and a resulting osmotic pressure in case of taurine. PMID:27195429

  15. Differential regulation of taurine biosynthesis in rainbow trout and Japanese flounder.

    PubMed

    Wang, Xuan; He, Gen; Mai, Kangsen; Xu, Wei; Zhou, Huihui

    2016-01-01

    Animals have varied taurine biosynthesis capability, which was determined by activities of key enzymes including cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD). However, whether CDO and CSD are differentially regulated across species remains unexplored. In the present study, we examined the regulations of CDO and CSD in rainbow trout and Japanese flounder, the two fish species with high and low taurine biosynthesis ability respectively. Our results showed that the expression of CDO was lower in rainbow trout but more responsive to cysteine stimulation compared to that in Japanese flounder. On the other hand, both the expression and catalytic efficiency (k(cat)) of CSD were higher in rainbow trout than those of Japanese flounder. A three-residue substrate recognition motif in rainbow trout CSD with sequence of F126/S146/Y148 was identified to be responsible for high k(cat), while that with sequence of F88/N108/F110 in Japanese flounder led to low k(cat), as suggested by site-directed mutagenesis studies. In summary, our results determined new aspects of taurine biosynthesis regulation across species. PMID:26880478

  16. Opposite effects of lead exposure on taurine- and HFS-induced LTP in rat hippocampus.

    PubMed

    Yu, Kuai; Yu, Shan-Shan; Ruan, Di-Yun

    2005-01-30

    The effect of lead exposure on taurine-induced long-term potentiation (LTP(TAU)) was examined and compared with high-frequency stimulation-induced one (LTP(HFS)). Field excitatory postsynaptic potentials (fEPSP) and fiber volley (FV) in area CA1 of hippocampal slice were recorded in control and lead-exposed rats. In contrast to the inhibitory effects of lead exposure on LTP(HFS), the amplitude of LTP(TAU) in the lead-exposed rats (199.3+/-13.7%, n=12) was significantly larger than that in controls (152.3+/-17.0%, n=12). It was also observed that taurine induced greater FV potentiation in lead-exposed rats (162.6+/-9.0%, n=10) than controls (132.1+/-6.9%, n=11). In addition, after a previous HFS, sequent perfusion of taurine could further increase the synaptic efficacy in lead-exposed rats. These results provide the first evidence that chronic lead exposure has opposite effects on the two types of LTP resulting from different lead toxicity sites. PMID:15639549

  17. Perinatal taurine exposure programs patterns of autonomic nerve activity responses to tooth pulp stimulation in adult male rats

    PubMed Central

    Khimsuksri, Sawita; Wyss, J. Michael; Thaeomor, Atcharaporn; Paphangkorakit, Jarin; Jirakulsomchok, Dusit; Roysommuti, Sanya

    2016-01-01

    Perinatal taurine excess or deficit influences adult health and disease, especially relative to the autonomic nervous system. This study tests the hypothesis that perinatal taurine exposure influences adult autonomic nervous system control of arterial pressure in response to acute electrical tooth pulp stimulation. Female Sprague-Dawley rats were fed normal rat chow with 3% β-alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS) or water alone (control, C) from conception to weaning. Their male offspring were fed normal rat chow and tap water throughout the experiment. At 8–10 weeks of age, blood chemistry, arterial pressure, heart rate and renal sympathetic nerve activity were measured in anesthetized rats. Age, body weight, mean arterial pressure, heart rate, plasma electrolytes, blood urea nitrogen, plasma creatinine and plasma cortisol were not significantly different among the three groups. Before tooth pulp stimulation, low (0.3–0.5 Hz) and high frequency (0.5–4.0 Hz) power spectral densities of arterial pressure were not significantly different among groups, while the power spectral densities of renal sympathetic nerve activity were significantly decreased in TD compared to control rats. Tooth pulp stimulation did not change arterial pressure, heart rate, renal sympathetic nerve and arterial pressure power spectral densities in the 0.3–4.0 Hz spectrum or renal sympathetic nerve firing rate in any group. In contrast, perinatal taurine imbalance disturbed very low frequency power spectral densities of both arterial pressure and renal sympathetic nerve activity (below 0.1 Hz), both before and after the tooth pulp stimulation. The power densities of TS were most sensitive to ganglionic blockade and central adrenergic inhibition, while those of TD were sensitive to both central and peripheral adrenergic inhibition. The present data indicate that perinatal taurine imbalance can lead to aberrant autonomic nervous system responses in

  18. Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11-/- mouse: transport and gene expression studies.

    PubMed

    Wang, Renxue; Liu, Lin; Sheps, Jonathan A; Forrest, Dana; Hofmann, Alan F; Hagey, Lee R; Ling, Victor

    2013-08-15

    The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice (abcb11-/-) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11-/- mice. Feeding UDCA to abcb11-/- mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11-/- mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11-/- mice. UDCA fed to abcb11-/- mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11-/- mice. PMID:23764895

  19. Taurine protects HK-2 cells from oxidized LDL-induced cytotoxicity via the ROS-mediated mitochondrial and p53-related apoptotic pathways

    SciTech Connect

    Chang, Chun-Yu; Shen, Chao-Yu; Kang, Chao-Kai; Sher, Yuh-Pyng; Sheu, Wayne H.-H.; Chang, Chia-Che; Lee, Tsung-Han

    2014-09-15

    Oxidized LDL (oxLDL) induces a pro-oxidative environment and promotes apoptosis, causing the progression of renal diseases in humans. Taurine is a semi-essential amino acid in mammals and has been shown to be a potent endogenous antioxidant. The kidney plays a pivotal role in maintaining the balance of taurine. However, the mechanisms underlying the protective effects of taurine against oxLDL-induced injury in renal epithelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effects of taurine on human proximal tubular epithelial (HK-2) cells exposed to oxLDL and explored the related mechanisms. We observed that oxLDL increased the contents of ROS and of malondialdehyde (MDA), which is a lipid peroxidation by-product that acts as an indicator of the cellular oxidation status. In addition, oxLDL induced cell death and apoptosis in HK-2 cells. Pretreatment with taurine at 100 μM significantly attenuated the oxLDL-induced cytotoxicity. We determined that oxLDL triggered the phosphorylation of ERK and, in turn, the activation of p53 and other apoptosis-related events, including calcium accumulation, destabilization of the mitochondrial permeability and disruption of the balance between pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins. The malfunctions induced by oxLDL were effectively blocked by taurine. Thus, our results suggested that taurine exhibits potential therapeutic activity by preventing oxLDL-induced nephrotoxicity. The inhibition of oxLDL-induced epithelial apoptosis by taurine was at least partially due to its anti-oxidant activity and its ability to modulate the ERK and p53 apoptotic pathways. - Highlights: • Oxidized LDL induced cytotoxicity and apoptosis in HK-2 cells. • Pretreatment with taurine attenuated oxLDL-induced nephrotoxicity. • Taurine protected against renal damages through inhibition of ROS generation. • Taurine prevented apoptosis through modulation of the p53 phosphorylation.

  20. [Hepatic encephalopathy].

    PubMed

    Jacques, Jérémie; Carrier, Paul; Debette-Gratien, Marilyne; Sobesky, Rodolphe; Loustaud-Ratti, Véronique

    2016-01-01

    Hepatic encephalopathy is a severe complication of liver cirrhosis and is an important therapeutic challenge, with a social and economic issue. If, now, the pathophysiology is not totally understood (main role of ammonia, but a better understanding of cerebral mechanisms), the clinical presentation is well-known. Some treatments are useful (disaccharides, treatment of the trigger) but their efficiency is limited. Nevertheless, the emergence of new treatments, such as non-absorbable antibiotics (rifaximin essentially), is an interesting therapeutic tool. PMID:26597584

  1. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  2. Hepatitis A - children

    MedlinePlus

    ... have the virus and do not practice good hygiene. Other common hepatitis virus infections include hepatitis B ... where diapers are changed to ensure that proper hygiene is followed. If your child gets hepatitis A, ...

  3. Hepatitis B virus (image)

    MedlinePlus

    Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

  4. Preventing hepatitis A

    MedlinePlus

    Hepatitis A is inflammation (irritation and swelling) of the liver caused by the hepatitis A virus. You can take several steps to ... reduce your risk of spreading or catching the hepatitis A virus: Always wash your hands thoroughly after ...

  5. What Is Hepatitis?

    MedlinePlus

    ... Twitter Facebook Google + iTunes Play Store What is hepatitis? Online Q&A Reviewed July 2016 Q: What ... Question and answer archives Submit a question World Hepatitis Day Know hepatitis - Act now Event notice Key ...

  6. Chemoprotective Effect of Taurine on Potassium Bromate-Induced DNA Damage, DNA-Protein Cross-Linking and Oxidative Stress in Rat Intestine

    PubMed Central

    Ahmad, Mir Kaisar; Khan, Aijaz Ahmed; Ali, Shaikh Nisar; Mahmood, Riaz

    2015-01-01

    Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. It induces multiple organ toxicity in humans and experimental animals and is a probable human carcinogen. The present study reports the protective effect of dietary antioxidant taurine on KBrO3-induced damage to the rat intestine. Animals were randomly divided into four groups: control, KBrO3 alone, taurine alone and taurine+ KBrO3. Administration of KBrO3 alone led to decrease in the activities of intestinal brush border membrane enzymes while those of antioxidant defence and carbohydrate metabolism were also severely altered. There was increase in DNA damage and DNA-protein cross-linking. Treatment with taurine, prior to administration of KBrO3, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. Histological studies supported these biochemical results showing extensive intestinal damage in KBrO3-treated animals and greatly reduced tissue injury in the taurine+ KBrO3 group. These results show that taurine ameliorates bromate induced tissue toxicity and oxidative damage by improving the antioxidant defence, tissue integrity and energy metabolism. Taurine can, therefore, be potentially used as a therapeutic/protective agent against toxicity of KBrO3 and related compounds. PMID:25748174

  7. Taurine zinc solid dispersions protect against cold-restraint stress-induced gastric ulceration by upregulating HSP70 and exerting an anxiolytic effect.

    PubMed

    Yu, Chuan; Mei, Xue-Ting; Zheng, Yan-Ping; Xu, Dong-Hui

    2015-09-01

    Pharmacological effects of solid dispersions (SDs) of a taurine zinc complex on gastric ulceration and anxiety were investigated. Pretreatment with taurine zinc (50, 100 or 200mg/kg) SDs dose-dependently protected rat gastric mucosa against cold-restraint stress (CRS)-induced gastric injury, and significantly attenuated increases in gastric mucosal H(+)K(+)-ATPase activity and lipid peroxidation and enhanced SOD activity. Taurine zinc also inhibited CRS-induced elevation of the serum stress hormones adrenocorticotropic hormone and corticosterone and upregulated HSP70 expression in the gastric mucosa. Moreover, taurine zinc (200mg/kg) SDs more potently protected the gastric mucosa from ulceration than the same dose of taurine, which may be attributed to a synergistic effect between taurine and zinc. Behavioral experiments in mice showed that taurine zinc SDs significantly increased the number of entries and time spent on the open arms in the elevated plus-maze test, time spent in the central area and total distance traveled in the open field test, and time spent and number of entries into the light compartment in the light/dark box test, indicative of reduced anxiety-like behaviors. This study demonstrates taurine zinc protected the gastric mucosa against CRS-induced gastric damage by decreasing oxidative stress, promoting endogenous HSP70 expression and attenuating psychological stress. PMID:26004529

  8. Osmotic regulation of neuronal activity: a new role for taurine and glial cells in a hypothalamic neuroendocrine structure.

    PubMed

    Hussy, N; Deleuze, C; Desarménien, M G; Moos, F C

    2000-10-01

    Maintenance of osmotic pressure is a primary regulatory process essential for normal cell function. The osmolarity of extracellular fluids is regulated by modifying the intake and excretion of salts and water. A major component of this regulatory process is the neuroendocrine hypothalamo-neurohypophysial system, which consists of neurons located in the paraventricular and supraoptic nuclei. These neurons synthesize the neurohormones vasopressin and oxytocin and release them in the blood circulation. We here review the mechanisms responsible for the osmoregulation of the activity of these neurons. Notably, the osmosensitivity of the supraoptic nucleus is described including the recent data that suggests an important participation of taurine in the transmission of the osmotic information. Taurine is an amino acid mainly known for its involvement in cell volume regulation, as it is one of the major inorganic osmolytes used by cells to compensate for changes in extracellular osmolarity. In the supraoptic nucleus, taurine is highly concentrated in astrocytes, and released in an osmodependent manner through volume-sensitive anion channels. Via its agonist action on neuronal glycine receptors, taurine is likely to contribute to the inhibition of neuronal activity induced by hypotonic stimuli. This inhibitory influence would complement the intrinsic osmosensitivity of supraoptic neurons, mediated by excitatory mechanoreceptors activated under hypertonic conditions. These observations extend the role of taurine from the regulation of cell volume to that of the whole body fluid balance. They also point to a new role of supraoptic glial cells as active components in a neuroendocrine regulatory loop. PMID:10828380

  9. Effect of taurine on oxidative stress and apoptosis-related protein expression in trinitrobenzene sulphonic acid-induced colitis

    PubMed Central

    Giriş, M; Depboylu, B; Doğru-Abbasoğlu, S; Erbil, Y; Olgaç, V; Alış, H; Aykaç-Toker, G; Uysal, M

    2008-01-01

    Ulcerative colitis (UC) is a multi-factorial inflammatory disease of the colon and rectum. The present study was undertaken to investigate the effect of taurine, an anti-oxidant amino acid, on oxidative stress and the expression of apoptosis-related proteins, pro-apoptotic Bax and anti-apoptotic B cell lymphoma-2 (Bcl-2) in colon tissue in rats with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Rats received taurine (1·5% w/v) in drinking water for 15 days before and 15 days after administration of TNBS solution. Then, colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels, and Bax and Bcl-2 expression were measured. TNBS-induced colitis caused significantly increased MPO activity and MDA levels and decreased GSH levels in colon tissue compared to controls. Increase in Bax expression and decrease in Bcl-2 expression were detected in colon of rats with TNBS-induced colitis. Taurine treatment was associated with amelioration in macroscopic and microscopic colitis scores, decreased colonic MPO activity and MDA levels and increased GSH levels in TNBS-induced colitis. In addition, taurine reduced the expression of Bax and prevented the loss of Bcl-2 proteins in colon tissue of rats with TNBS-induced colitis. The results of this study show that taurine administration may exert beneficial effects in UC by decreasing inflammatory reactions, oxidative stress and apoptosis. PMID:18241224

  10. Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

    MedlinePlus

    ... of chronic liver disease, cirrhosis, viral hepatitis, and liver cancer make liver disease one of the 10 leading ... disease are decreasing, those for viral hepatitis and liver cancer are on the rise, both in the U.S. ...

  11. Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance

    PubMed Central

    2010-01-01

    Background High intake of dietary fructose is accused of being responsible for the development of the insulin resistance (IR) syndrome. Concern has arisen because of the realization that fructose, at elevated concentrations, can promote metabolic changes that are potentially deleterious. Among these changes is IR which manifests as a decreased biological response to normal levels of plasma insulin. Methods Oral glucose tolerance tests (OGTT) were carried out, homeostasis model assessment of insulin resistance (HOMA) was calculated, homocysteine (Hcy), lipid concentrations and markers of oxidative stress were measured in male Wistar rats weighing 170-190 g. The rats were divided into four groups, kept on either control diet or high fructose diet (HFD), and simultaneously supplemented with 300 mg/kg/day taurine via intra-peritoneal (i.p.) route for 35 days. Results Fructose-fed rats showed significantly impaired glucose tolerance, impaired insulin sensitivity, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia (HHcy), lower total antioxidant capacity (TAC), lower paraoxonase (PON) activity, and higher nitric oxide metabolites (NOx) concentration, when compared to rats fed on control diet. Supplementing the fructose-fed rats with taurine has ameliorated the rise in HOMA by 56%, triglycerides (TGs) by 22.5%, total cholesterol (T-Chol) by 11%, and low density lipoprotein cholesterol (LDL-C) by 21.4%. Taurine also abolished any significant difference of TAC, PON activity and NOx concentration among treated and control groups. TAC positively correlated with PON in both rats fed on the HFD and those received taurine in addition to the HFD. Fructose-fed rats showed 34.7% increase in Hcy level. Taurine administration failed to prevent the observed HHcy in the current dosage and duration. Conclusion Our results indicate that HFD could induce IR which could further result in metabolic syndrome (MS), and that taurine has a protective role against the metabolic

  12. Protect Yourself from Hepatitis

    MedlinePlus

    ... develop yellowish eyes and skin. All the hepatitis viruses can cause acute, or short-term, hepatitis. Some can also cause chronic hepatitis, in which the infection lasts a long time, sometimes for your whole life. Chronic hepatitis can eventually lead to scarring of ...

  13. Hepatic osteodystrophy.

    PubMed

    Gatta, Angelo; Verardo, Alberto; Di Pascoli, Marco; Giannini, Sandro; Bolognesi, Massimo

    2014-09-01

    Metabolic disturbances of bone are frequent in patients with chronic liver disease. The prevalence of osteoporosis among patients with advanced chronic liver disease is reported between 12% and 55%; it is higher in primary biliary cirrhosis. All patients with advanced liver disease should be screened for osteoporosis with a densitometry, especially if the etiology is cholestatic and in the presence of other risk factors. Clinical relevance of hepatic osteodystrophy increases after liver transplantation. After liver transplant, a rapid loss of bone mineral density can be detected in the first 6 months, followed by stabilization and slight improvement of the values. At the time of transplantation, bone density values are very important prognostic factors. Therapy of hepatic osteodystrophy is based primarily on the control of risk factors: cessation of tobacco and alcohol assumption, reduction of caffeine ingestion, exercise, supplementation of calcium and vitamin D, limitation of drugs such as loop diuretics, corticosteroids, cholestyramine. Bisphosphonates have been proposed for the therapy of osteoporosis in patients with liver disease, particularly after liver transplantation. The possible side effects of oral administration of bisphosphonates, such as the occurrence of esophageal ulcerations, are of particular concern in patients with liver cirrhosis and portal hypertension, due to the risk of gastrointestinal hemorrhage from ruptured esophageal varices, although this risk is probably overestimated. PMID:25568651

  14. [Hepatic encephalopathy].

    PubMed

    Festi, Davide; Marasco, Giovanni; Ravaioli, Federico; Colecchia, Antonio

    2016-07-01

    Hepatic encephalopathy (HE) is a common complication of liver cirrhosis and it can manifest with a broad spectrum of neuropsychiatric abnormalities of varying severity, acuity and time course with important clinical implications. According to recent guidelines, HE has been classified into different types, depending on the severity of hepatic dysfunction, the presence of porto-systemic shunts and the number of previous episodes or persistent manifestations. From a clinical point of view, HE can be recognized as unimpaired, covert (that deals with minimal and grade 1 according to the grading of mental state), and overt (that is categorized from grade 2 to grade 4). Different and only partially known pathogenic mechanisms have been identified, comprising ammonia, inflammatory cytokines, benzodiazepine-like compounds and manganese deposition. Different therapeutic strategies are available for treating HE, in particular the overt HE, since covert HE needs to be managed case by case. Recognition and treatment of precipitating factors represent fundamental part of the management. The more effective treatments, which can be performed separately or combined, are represented by non-absorbable disaccharides (lactulose and lactitol) and the topic antibiotic rifaximin; other possible therapies, mainly used in patients non responders to previous treatments, are represented by branched chain amino acids and metabolic ammonia scavengers. PMID:27571468

  15. High-temperature Raman study of L-alanine, L-threonine and taurine crystals related to thermal decomposition

    NASA Astrophysics Data System (ADS)

    Cavaignac, A. L. O.; Lima, R. J. C.; Façanha Filho, P. F.; Moreno, A. J. D.; Freire, P. T. C.

    2016-03-01

    In this work high-temperature Raman spectra are used to compare temperature dependence of the lattice mode wavenumber of L-alanine, L-threonine and taurine crystals. Anharmonic effects observed are associated with intermolecular N-H· · ·O hydrogen bond that plays an important role in thermal decomposition process of these materials. Short and strong hydrogen bonds in L-alanine crystal were associated with anharmonic effects in lattice modes leading to low thermal stability compared to taurine crystals. Connection between thermal decomposition process and anharmonic effects is furnished for the first time.

  16. Taurine Bromamine: Reactivity of an Endogenous and Exogenous Anti-Inflammatory and Antimicrobial Amino Acid Derivative

    PubMed Central

    Bertozo, Luiza De Carvalho; Morgon, Nelson Henrique; De Souza, Aguinaldo Robinson; Ximenes, Valdecir Farias

    2016-01-01

    Taurine bromamine (Tau-NHBr) is produced by the reaction between hypobromous acid (HOBr) and the amino acid taurine. There are increasing number of applications of Tau-NHBr as an anti-inflammatory and microbicidal drug for topical usage. Here, we performed a comprehensive study of the chemical reactivity of Tau-NHBr with endogenous and non-endogenous compounds. Tau-NHBr reactivity was compared with HOBr, hypochlorous acid (HOCl) and taurine chloramine (Tau-NHCl). The second-order rate constants (k2) for the reactions between Tau-NHBr and tryptophan (7.7 × 102 M−1s−1), melatonin (7.3 × 103 M−1s−1), serotonin (2.9 × 103 M−1s−1), dansylglycine (9.5 × 101 M−1s−1), tetramethylbenzidine (6.4 × 102 M−1s−1) and H2O2 (3.9 × M−1s−1) were obtained. Tau-NHBr demonstrated the following selectivity regarding its reactivity with free amino acids: tryptophan > cysteine ~ methionine > tyrosine. The reactivity of Tau-NHBr was strongly affected by the pH of the medium (for instance with dansylglycine: pH 5.0, 1.1 × 104 M−1s−1, pH 7.0, 9.5 × 10 M−1s−1 and pH 9.0, 1.7 × 10 M−1s−1), a property that is related to the formation of the dibromamine form at acidic pH (Tau-NBr2). The formation of singlet oxygen was observed in the reaction between Tau-NHBr and H2O2. Tau-NHBr was also able to react with linoleic acid, but with low efficiency compared with HOBr and HOCl. Compared with HOBr, Tau-NHBr was not able to react with nucleosides. In conclusion, the following reactivity sequence was established: HOBr > HOCl > Tau-NHBr > Tau-NHCl. These findings can be very helpful for researchers interested in biological applications of taurine haloamines. PMID:27110829

  17. Taurine Bromamine: Reactivity of an Endogenous and Exogenous Anti-Inflammatory and Antimicrobial Amino Acid Derivative.

    PubMed

    De Carvalho Bertozo, Luiza; Morgon, Nelson Henrique; De Souza, Aguinaldo Robinson; Ximenes, Valdecir Farias

    2016-01-01

    Taurine bromamine (Tau-NHBr) is produced by the reaction between hypobromous acid (HOBr) and the amino acid taurine. There are increasing number of applications of Tau-NHBr as an anti-inflammatory and microbicidal drug for topical usage. Here, we performed a comprehensive study of the chemical reactivity of Tau-NHBr with endogenous and non-endogenous compounds. Tau-NHBr reactivity was compared with HOBr, hypochlorous acid (HOCl) and taurine chloramine (Tau-NHCl). The second-order rate constants (k₂) for the reactions between Tau-NHBr and tryptophan (7.7 × 10² M(-1)s(-1)), melatonin (7.3 × 10³ M(-1)s(-1)), serotonin (2.9 × 10³ M(-1)s(-1)), dansylglycine (9.5 × 10¹ M(-1)s(-1)), tetramethylbenzidine (6.4 × 10² M(-1)s(-1)) and H₂O₂ (3.9 × M(-1)s(-1)) were obtained. Tau-NHBr demonstrated the following selectivity regarding its reactivity with free amino acids: tryptophan > cysteine ~ methionine > tyrosine. The reactivity of Tau-NHBr was strongly affected by the pH of the medium (for instance with dansylglycine: pH 5.0, 1.1 × 10⁴ M(-1)s(-1), pH 7.0, 9.5 × 10 M(-1)s(-1) and pH 9.0, 1.7 × 10 M(-1)s(-1)), a property that is related to the formation of the dibromamine form at acidic pH (Tau-NBr₂). The formation of singlet oxygen was observed in the reaction between Tau-NHBr and H₂O₂. Tau-NHBr was also able to react with linoleic acid, but with low efficiency compared with HOBr and HOCl. Compared with HOBr, Tau-NHBr was not able to react with nucleosides. In conclusion, the following reactivity sequence was established: HOBr > HOCl > Tau-NHBr > Tau-NHCl. These findings can be very helpful for researchers interested in biological applications of taurine haloamines. PMID:27110829

  18. Genetics is a major determinant of expression of the human hepatic uptake transporter OATP1B1, but not of OATP1B3 and OATP2B1

    PubMed Central

    2013-01-01

    Background Organic anion transporting polypeptide (OATP) 1B1, OATP1B3, and OATP2B1 (encoded by SLCO1B1, SLCO1B3, SLCO2B1) mediate the hepatic uptake of endogenous compounds like bile acids and of drugs, for example, the lipid-lowering atorvastatin, thereby influencing hepatobiliary elimination. Here we systematically elucidated the contribution of SLCO variants on expression of the three hepatic OATPs under consideration of additional important covariates. Methods Expression was quantified by RT-PCR and immunoblotting in 143 Caucasian liver samples. A total of 109 rare and common variants in the SLCO1B3-SLCO1B1 genomic region and the SLCO2B1 gene were genotyped by MALDI-TOF mass spectrometry and genome-wide SNP microarray technology. SLCO1B1 haplotypes affecting hepatic OATP1B1 expression were associated with pharmacokinetic data of the OATP1B1 substrate atorvastatin (n = 82). Results Expression of OATP1B1, OATP1B3, and OATP2B1 at the mRNA and protein levels showed marked interindividual variability. All three OATPs were expressed in a coordinated fashion. By a multivariate regression analysis adjusted for non-genetic and transcription covariates, increased OATP1B1 expression was associated with the coding SLCO1B1 variant c.388A > G (rs2306283) even after correction for multiple testing (P = 0.00034). This held true for haplotypes harboring c.388A > G but not the functional variant c.521T > C (rs4149056) associated with statin-related myopathy. c.388A > G also significantly affected atorvastatin pharmacokinetics. SLCO variants and non-genetic and regulatory covariates together accounted for 59% of variability of OATP1B1 expression. Conclusions Our results show that expression of OATP1B1, but not of OATP1B3 and OATP2B1, is significantly affected by genetic variants. The SLCO1B1 variant c.388A > G is the major determinant with additional consequences on atorvastatin plasma levels. PMID:23311897

  19. Novel mechanism of transcriptional repression of the human ATP binding cassette transporter A1 gene in hepatic cells by the winged helix/forkhead box transcription factor A2.

    PubMed

    Thymiakou, Efstathia; Kardassis, Dimitris

    2014-06-01

    ATP binding cassette transporter A1 (ABCA1) plays a key role in the biogenesis of HDL by promoting the efflux of cellular cholesterol and phospholipids to lipid free apoA-I. Mutations in the ABCA1 gene cause Tangier disease which is characterized by near or complete absence of circulating plasma HDL. In the present study we show that the winged helix/forkhead box containing transcription factor A2 (FOXA2) shown previously to play a role in glucose and bile acid homeostasis in the liver and in energy utilization in adipose tissue is a negative modulator of ABCA1 gene expression in hepatic cells. We show that the ABCA1 promoter contains three FOXA2 binding elements in the proximal region. Two of the sites are localized in a region of the ABCA1 promoter enriched in binding elements for transcriptional repressor proteins whereas the third site is the core of the TATA element of the ABCA1 promoter. Inhibition of FOXA2 binding to the ABCA1 promoter by site-directed mutagenesis or FOXA2 gene expression by siRNA was associated with increased ABCA1 promoter activity and protein levels. Overexpression of FOXA2 inhibited both the constitutive ABCA1 gene expression as well as ABCA1 gene induction by oxysterols and retinoids via nuclear receptors LXRα/RXRα. In summary, the present study identifies transcription factor FOXA2 as a negative modulator of ABCA1 gene expression in hepatic cells and reveals a novel mechanism of transcriptional repression by FOXA2 which involves the TATA element of the ABCA1 gene. PMID:24807696

  20. Rapid analysis of taurine in energy drinks using amino acid analyzer and Fourier transform infrared (FTIR) spectroscopy as basis for toxicological evaluation.

    PubMed

    Triebel, S; Sproll, C; Reusch, H; Godelmann, R; Lachenmeier, D W

    2007-09-01

    So-called energy drinks with very high amounts of taurine (up to 4000 mg/l are usually granted by certificates of exemption) are increasingly offered on the market. To control the currently valid maximum limits of taurine in energy drinks, a simple and rapid analytical method is required to use it routinely in food monitoring. In this article, we describe a fast and efficient analytical method (FTIR-spectroscopy) that is able to reliably characterize and quantify taurine in energy drinks. The determination of taurine in energy drinks by FTIR was compared with amino acid analyzer (ion chromatography with ninhydrin-postcolumn derivatization). During analysis of 80 energy drinks, a median concentration of 3180 mg/l was found in alcohol-free products, 314 mg/l in energy drinks with spirits, 151 mg/l in beer-containing drinks and 305 mg/l in beverages with wine. Risk analysis of these products is difficult due to the lack of valid toxicological information about taurine and its interferences with other ingredients of energy drinks (for example caffeine and alcohol). So far, the high taurine concentrations of energy drinks in comparison to the rest of the diet are scientifically doubtful, as the advertised physiological effects and the value of supplemented taurine are unproven. PMID:17051421

  1. Effects of taurine depletion on cell migration and NCAM expression in cultures of dissociated mouse cerebellum and N2A cells.

    PubMed

    Maar, T E; Lund, T M; Gegelashvili, G; Hartmann-Petersen, R; Moran, J; Pasantes-Morales, H; Berezin, V; Bock, E; Schousboe, A

    1998-01-01

    Cultures of dissociated cerebellum from 5- to 6-day-old mice as well as of the N2A neuronal cell line were exposed to guanidino ethane sulfonate (GES, 2-5 mM) to reduce the cellular taurine content. Control cultures were kept in culture medium or medium containing 2-5 mM GES plus 2-5 mM taurine to restore the intracellular taurine content. Taurine depletion led to changes in the expression of certain splice variants of NCAM mRNA such as the AAG and the VASE containing forms, while no differences were seen in the expression of the three forms of NCAM protein. In the N2A cells taurine depletion led to a decreased migration rate of the cells. The results suggest that the reduced migration rate of neurons caused by taurine depletion may be correlated to changes in expression of certain adhesion molecules such as NCAM. Moreover, taurine appears to be involved in regulation of transcription processes. PMID:9871488

  2. Role of constitutive androstane receptor in Toll-like receptor-mediated regulation of gene expression of hepatic drug-metabolizing enzymes and transporters.

    PubMed

    Shah, Pranav; Guo, Tao; Moore, David D; Ghose, Romi

    2014-01-01

    Impairment of drug disposition in the liver during inflammation has been attributed to downregulation of gene expression of drug-metabolizing enzymes (DMEs) and drug transporters. Inflammatory responses in the liver are primarily mediated by Toll-like receptors (TLRs). We have recently shown that activation of TLR2 or TLR4 by lipoteichoic acid (LTA) and lipopolysaccharide (LPS), respectively, leads to the downregulation of gene expression of DMEs/transporters. However, the molecular mechanism underlying this downregulation is not fully understood. The xenobiotic nuclear receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR), regulate the expression of DMEs/transporter genes. Downregulation of DMEs/transporters by LTA or LPS was associated with reduced expression of PXR and CAR genes. To determine the role of CAR, we injected CAR(+/+) and CAR(-/-) mice with LTA or LPS, which significantly downregulated (~40%-60%) RNA levels of the DMEs, cytochrome P450 (Cyp)3a11, Cyp2a4, Cyp2b10, uridine diphosphate glucuronosyltransferase 1a1, amine N-sulfotransferase, and the transporter, multidrug resistance-associated protein 2, in CAR(+/+) mice. Suppression of most of these genes was attenuated in LTA-treated CAR(-/-) mice. In contrast, LPS-mediated downregulation of these genes was not attenuated in CAR(-/-) mice. Induction of these genes by mouse CAR activator 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene was sustained in LTA- but not in LPS-treated mice. Similar observations were obtained in humanized CAR mice. We have replicated these results in primary hepatocytes as well. Thus, LPS can downregulate DME/transporter genes in the absence of CAR, whereas the effect of LTA on these genes is attenuated in the absence of CAR, indicating the potential involvement of CAR in LTA-mediated downregulation of DME/transporter genes. PMID:24194512

  3. Viral hepatitis: Indian scenario.

    PubMed

    Satsangi, Sandeep; Chawla, Yogesh K

    2016-07-01

    Viral hepatitis is a cause for major health care burden in India and is now equated as a threat comparable to the "big three" communicable diseases - HIV/AIDS, malaria and tuberculosis. Hepatitis A virus and Hepatitis E virus are predominantly enterically transmitted pathogens and are responsible to cause both sporadic infections and epidemics of acute viral hepatitis. Hepatitis B virus and Hepatitis C virus are predominantly spread via parenteral route and are notorious to cause chronic hepatitis which can lead to grave complications including cirrhosis of liver and hepatocellular carcinoma. Around 400 million people all over the world suffer from chronic hepatitis and the Asia-Pacific region constitutes the epicentre of this epidemic. The present article would aim to cover the basic virologic aspects of these viruses and highlight the present scenario of viral hepatitis in India. PMID:27546957

  4. Diabetes and Hepatitis B Vaccination

    MedlinePlus

    Diabetes and Hepatitis B Vaccination Information for Diabetes Educators What is hepatitis B? Hepatitis B is a contagious liver disease that results from infection with the hepatitis B virus. When first infected, a person can develop ...

  5. Hepatitis B Blood Tests: FAQ

    MedlinePlus

    ... 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working on ... people living with hepatitis B. Learn About Hepatitis B in 10 Other Languages . Resource Video See More ...

  6. Hepatitis Information for the Public

    MedlinePlus

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis Information for the Public Recommend on Facebook Tweet ...

  7. Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: Effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway

    SciTech Connect

    Ahmed, Maha A.E.

    2015-02-01

    The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free β-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoate (10 mg/kg/week, I.M.), taurine (100 mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3β-HSD, and 17β-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats. - Highlights: • Nandrolone decanoate (ND) disrupts sperm profile and steroidogenesis in rats. • ND upregulates gene expression of inflammatory and apoptotic markers. • Taurine normalizes sperm profile and serum testosterone level

  8. Taurine as a marker for the identification of natural Calculus Bovis and its substitutes.

    PubMed

    Shimada, Kayoko; Azuma, Yuko; Kawase, Masaya; Takahashi, Toshiharu; Schaffer, Stephen W; Takahashi, Kyoko

    2013-01-01

    Calculus Bovis (C. Bovis) is a commonly used animal-derived therapeutic preparation. To meet the increasing clinical demand for the preparation, two artificial substitutes for Bos Taurus have been introduced in China: artificial C. Bovis and in vitro cultured C. Bovis. However, information on their efficacy and safety is inadequate. Therefore, we investigated the biological differences between the commonly used natural preparation and its two substitutes, with the aim of not only identifying the differences but also providing a procedure to distinguish between the different preparations.In the study, we prepared 9 natural C. Bovis, 2 artificial C. Bovis, and 2 in vitro cultured C. Bovis preparations for evaluation. Differences were noted between the three preparations relative to their effect on viability of cardiac fibroblasts from 1-day-old Wistar rats. Although natural C. Bovis had no effect on cell viability, 1-h treatment of the cells with 0.25 mg/ml of the substitutes significantly reduced cell viability, as detected by the MTS assay. Based on liquid chromatography and inductively coupled plasma mass spectrometry, the preparations also differed in composition. Indeed, the substitutes contained more taurine, cholic acid, iron, magnesium, and calcium than the natural preparations. They also differed spectroscopically.The present results reveal significant biological differences between natural C. Bovis and two of its substitutes. Since the substitutes appear to contain more taurine, cholic acid, and elements, these constituents may serve as markers to distinguish between natural C. Bovis and its substitutes. PMID:23392879

  9. Assessing signatures of selection through variation in linkage disequilibrium between taurine and indicine cattle

    PubMed Central

    2014-01-01

    Background Signatures of selection are regions in the genome that have been preferentially increased in frequency and fixed in a population because of their functional importance in specific processes. These regions can be detected because of their lower genetic variability and specific regional linkage disequilibrium (LD) patterns. Methods By comparing the differences in regional LD variation between dairy and beef cattle types, and between indicine and taurine subspecies, we aim at finding signatures of selection for production and adaptation in cattle breeds. The VarLD method was applied to compare the LD variation in the autosomal genome between breeds, including Angus and Brown Swiss, representing taurine breeds, and Nelore and Gir, representing indicine breeds. Genomic regions containing the top 0.01 and 0.1 percentile of signals were characterized using the UMD3.1 Bos taurus genome assembly to identify genes in those regions and compared with previously reported selection signatures and regions with copy number variation. Results For all comparisons, the top 0.01 and 0.1 percentile included 26 and 165 signals and 17 and 125 genes, respectively, including TECRL, BT.23182 or FPPS, CAST, MYOM1, UVRAG and DNAJA1. Conclusions The VarLD method is a powerful tool to identify differences in linkage disequilibrium between cattle populations and putative signatures of selection with potential adaptive and productive importance. PMID:24592996

  10. Thermodynamic characteristics of the acid-base equilibria of taurine in aqueous solutions, according to calorimetry data

    NASA Astrophysics Data System (ADS)

    Gridchin, S. N.; Shekhanov, R. F.; Pyreu, D. F.

    2015-02-01

    Enthalpies of the neutralization and protonation of taurine (HL) are measured by direct calorimetry at 298.15 K and ionic strengths of 0.3, 0.5, and 1.0 (KNO3). The standard thermodynamic characteristics of HL protolytic equilibria are calculated.

  11. Effect of supplemental taurine on juvenile channel catfish Ictalurus punctatus growth and survival after challenge with Edwardsiella ictaluri

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Juvenile channel catfish, Ictalurus punctatus, were fed a basal diet that contained major protein (soybean meal, cottonseed meal) and energy (ground corn grain) ingredients that were derived from plant sources. Plant-source ingredients are considered to be low (< 5 ppm) for taurine content. In add...

  12. Antiobesity and hypolipidemic effects of lotus leaf hot water extract with taurine supplementation in rats fed a high fat diet

    PubMed Central

    2010-01-01

    Background Lotus (Nelumbo nucifera) leaf has been used to treat obesity. The purpose of this study was to investigate the antiobesity and hypolipidemic effects of lotus leaf hot water extract with taurine supplementation in high fat diet-induced obese rats. Methods Four week-old male Sprague-Dawley rats were randomly divided into four groups with 8 rats in each group for a period of 6 weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus leaf hot water extract, HFL group; high fat diet + lotus leaf hot water extract + taurine, HFLT group). Lotus leaf hot water extract was orally administrated to HFL and HFLT groups and the same amount of distilled water was orally administered (400 mg/kg/day) to N and HF groups. Taurine was supplemented by dissolving in feed water (3% w/v). Results The body weight gain and relative weights of epididymal and retroperitoneal adipose tissues were significantly lower in N, HFL and HFLT groups compared to HF group. HFL and HFLT groups showed lower concentrations of total cholesterol, triglyceride and low density lipoprotein cholesterol in serum. HFLT group showed higher the ratio of high density lipoprotein cholesterol/total cholesterol compared to HFL group. HFLT group showed better blood lipid profiles compared to HFL group. Conclusions Lotus leaf hot water extract with taurine supplementation showed antiobesity and hypolipidemic effects in high fat diet-induced obese rats, which was more effective than lotus leaf hot water extract alone. PMID:20804619

  13. The role of Ca(2+) mediated signaling pathways on the effect of taurine against Streptococcus uberis infection.

    PubMed

    Dai, Bin; Zhang, Jinqiu; Liu, Ming; Lu, Jinye; Zhang, Yuanshu; Xu, Yuanyuan; Miao, Jinfeng; Yin, Yulong

    2016-08-30

    To provide insight into the mechanisms of taurine attenuation of pro-inflammatory response in mouse mammary epithelial cell line (EpH4-Ev, purchased by ATCC, USA) after Streptococcus uberis (S. uberis, 0140J) challenge, we infected MECs with S. uberis (2.5×10(7)cfumL(-1), MOI=10) for 3h and quantified changes in TLR-2 and calcium (Ca(2+)) mediated signaling pathways. The results indicate that S. uberis infection significantly increases the expression of TLR-2, intracellular Ca(2+) levels, PLC-γ1 and PKC-α, the activities of transcription factors NF-κB and NFAT, and related cytokines (TNF-α, IL-1β, IL-6, G-CSF, IL-2, KC, IL-15, FasL, MCP-1, and LIX) in culture supernatants. Taurine administration downregulated all these indices, the activities of NF-κB and NFAT. Cytokine secretions were similar using special PKC inhibitor Go 6983 and NFAT inhibitor VIVIT. Our data indicate that S. uberis infection induces pro-inflammatory response of MECs through a TLR-2 mediated signaling pathway. In addition, taurine can prevent MEC damage by affecting both PLC-γ1-Ca(2+)-PKC-α-NF-κB and PLC-γ1-Ca(2+)-NFATs signaling pathways. This is the first report to demonstrate the mechanisms of taurine attenuated pro-inflammatory response in MECs after S. uberis challenge. PMID:27527761

  14. Taurine supplementation to alternative dietary proteins used in fish meal replacement enhances growth of juvenile cobia (Rachycentron canadum)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two separate 8 week feeding trials were conducted to examine the impacts of fish meal replacement with an organically certifiable yeast-based protein source with and without supplementation of methionine, tryptophan, and taurine to diets for juvenile cobia. In the first trial, diets were formulated ...

  15. Taurine protects hamster bronchioles from acute NO2-induced alterations. A histologic, ultrastructural, and freeze-fracture study.

    PubMed Central

    Gordon, R. E.; Shaked, A. A.; Solano, D. F.

    1986-01-01

    In this study the authors describe the use of dietary taurine to protect hamster lung epithelium from acute nitrogen dioxide (NO2) injury. The conclusions were based on histologic, ultrastructural, and freeze-fracture analyses. Hamsters were pretreated for 14 days with 0.5% taurine in their drinking water. They were then exposed to either 7 or 30 ppm NO2 for 24 hours. The lungs from animals of these experimental groups were compared with those from hamsters treated with only NO2, and those given only taurine and with untreated controls. After treatment, hamsters were anesthetized and perfusion-fixed through the right side of the heart with a solution containing 1% glutaraldehyde, 4% paraformaldehyde, and 0.2 M cacodylate. The trachea and lungs were removed en bloc and stored overnight in cacodylate buffer at 4 C. Terminal and respiratory bronchioles, including alveolar ducts and peribronchiolar alveoli, were dissected from each lobe and processed for embedding in Epon and freeze-fracture replication. Light and transmission electron microscopy revealed the typical inflammatory cell infiltrate in the bronchiolar and alveolar duct regions in the lungs of hamsters exposed to NO2. The bronchiolar epithelium appeared flattened because of loss and breakage of cilia on ciliated cells and apical protrusions of Clara cells. Clara-cell secretory granules were reduced or absent. Freeze-fracture replicas of tight junctions of bronchiolar epithelium analyzed by morphometric techniques demonstrated a reduction and fragmentation of fibrils. Only animals exposed to 30 ppm NO2 exhibited physiologic intercellular penetration of horseradish peroxidase. Hamsters pretreated with taurine and then exposed to NO2 showed none of these alterations. They exhibited the same morphologic features as the untreated controls and the hamsters treated only with taurine. On the basis of this evidence, it is suggested that prophylactic dietary taurine can prevent acute NO2-induced morphologic lung

  16. [Viral hepatitis in travellers].

    PubMed

    Abreu, Cândida

    2007-01-01

    Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

  17. Hepatic abscesses

    PubMed Central

    Rajagopalan, S.; Langer, V.

    2012-01-01

    Hepatic abscesses are potentially lethal diseases if early diagnosis and treatment are not instituted. They are prevalent all over the globe and pyogenic abscesses are predominant over amoebic. With better control of intra abdominal and systemic infections by a spectrum of antibiotics, aetiology of pyogenic abscesses are secondary to interventions and diseases in the biliary tree to a large extent today. The common organisms isolated are the Gram negative group. Amoebic abscesses continue to plague some regions of the world where hygiene and sanitation are questionable. Over the years, diagnosis, treatment and prognosis have evolved remarkably. Imaging modalities like ultrasonography and CT scan have become the cornerstone of diagnosis. The absence of ionizing radiation makes MRI an attractive alternative in patients who require multiple follow up scans. Serological testing in amoebic abscesses has become more reliable. Though antibiotics have remained the principal modality of management, percutaneous drainage of abscesses have vastly improved the chances of cure and bring down the morbidity drastically in pyogenic abscesses. Amoebic abscesses respond well to medical treatment with nitroimidazoles, and minimally invasive surgical drainage is an option in cases where open surgery is indicated. PMID:24532886

  18. Hepatitis B Test

    MedlinePlus

    ... IgM; anti-HBe; Hepatitis B e Antibody; HBV DNA Formal name: Hepatitis B Virus Testing Related tests: ... produced by the virus, and others detect viral DNA . The main uses for HBV tests include: To ...

  19. Hepatitis Foundation International

    MedlinePlus

    ... partner – it's your best friend. Welcome. The Hepatitis Foundation International (HFI) is a 501 (c) 3 non- ... and cures is your participation in the Hepatitis Foundation International Registry. Whether you are affected, a caregiver, ...

  20. Hepatitis A - children

    MedlinePlus

    ... hepatitis A. Children can get hepatitis A at day care center from other children or from child care ... treatment with immunoglobulin therapy. If your child attends day care: Make sure the children and staff at the ...

  1. Hepatitis C (image)

    MedlinePlus

    Hepatitis C is a virus-caused liver inflammation which may cause jaundice, fever and cirrhosis. Persons who are most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs ...

  2. Hepatitis E Pathogenesis.

    PubMed

    Lhomme, Sébastien; Marion, Olivier; Abravanel, Florence; Chapuy-Regaud, Sabine; Kamar, Nassim; Izopet, Jacques

    2016-01-01

    Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years. PMID:27527210

  3. Treating hepatitis C.

    PubMed

    Hanson, Karmen

    2014-10-01

    (1) New treatments for hepatitis C are curing more people than before. (2) Baby boomers make up an estimated 75 percent of all cases of hepatitis C. (3) Medicare and some insurance plans cover screening for hepatitis C as a preventive service without a copayment. PMID:25514812

  4. Hepatitis E Pathogenesis

    PubMed Central

    Lhomme, Sébastien; Marion, Olivier; Abravanel, Florence; Chapuy-Regaud, Sabine; Kamar, Nassim; Izopet, Jacques

    2016-01-01

    Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years. PMID:27527210

  5. Hepatitis B (HBV)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Hepatitis B (HBV) KidsHealth > For Teens > Hepatitis B (HBV) Print A A A Text Size ... Prevented? How Is It Treated? What Is It? Hepatitis (pronounced: hep-uh-TIE-tiss) is a disease ...

  6. Variant innate immune responses of mammary epithelial cells to challenge by Staphylococcus aureus, Escherichia coli and the regulating effect of taurine on these bioprocesses.

    PubMed

    Zheng, Liuhai; Xu, Yuanyuan; Lu, Jinye; Liu, Ming; Bin Dai; Miao, Jinfeng; Yin, Yulong

    2016-07-01

    Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are important pathogens causing subclinical and clinical bovine mastitis, respectively. Taurine, an organic acid found in animal tissues, has been used for the treatment of various superficial infections and chronic inflammations. We challenged a bovine mammary epithelial cell (MEC) line (MAC-T) or a mouse mammary epithelial cell line (EpH4-Ev) with either E. coli or S. aureus and compared the responses of MECs to these 2 pathogens. We also examined the regulatory effects of taurine on these responses. Receptor analyses showed that both TLR2 and TLR4 are upregulated upon exposure to either E. coli or S. aureus. Taurine pre-treatment dampened upregulation to some extent. E. coli and S. aureus stimulated comparable levels of ROS, which could be inhibited by taurine pre-treatment. E. coli infection elicited a dramatic change in iNOS expression. Taurine significantly decreased iNOS expression in the S. aureus challenged group. Protein microarray demonstrated that 32/40 and 8/40 inflammatory molecules/mediators were increased after E. coli or S. aureus challenge, respectively. The fold changes of most molecules were higher in the E. coli infection group than that in the S. aureus infection group. Taurine negatively regulated the inflammatory profile in both bacterial infections. Pro-inflammatory cytokines (such as TNF-α) connected with TLR activation were down-regulated by taurine pre-treatment. The influence of TAK-242 and OxPAPC on cytokine/molecule expression profiles to E. coli challenge are different than to S. aureus. Some important factors (MyD88, TNF-α, IL-1β, iNOS and IL-6) mediated by TLR activation were suppressed either in protein microarray or special assay (PCR/kits) or both. TAK-242 restrained ROS production and NAGase activity similar to the effect of taurine in E. coli challenge groups. The detection of 3 indices (T-AOC, SOD and MDA) reflecting oxidative stress in vivo, showed that

  7. Synthesis of hepatic lipase in liver and extrahepatic tissues

    SciTech Connect

    Doolittle, M.H.; Wong, H.; Davis, R.C.; Schotz, M.C.

    1987-11-01

    Immunoprecipitations of hepatic lipase from pulse-labeled rat liver have demonstrated that hepatic lipase is synthesized in two distinct molecular weight forms, HL-I (Mr = 51,000) and HL-II (Mr = 53,000). Both forms are immunologically related to purified hepatic lipase, but not to lipoprotein lipase. HL-I and HL-II are also kinetically related and represent different stages of intracellular processing. Glycosidase experiments suggest that HL-I is the high mannose microsomal form of the mature, sialylated HL-II enzyme. Hepatic lipase activity was detected in liver and adrenal gland but was absent in brain, heart, kidney, testes, small intestine, lung, and spleen. The adrenal and liver lipase activities were inhibited in a similar dose-dependent manner by hepatic lipase antiserum. Immunoblot analysis of partially purified adrenal lipase showed an immunoreactive band co-migrating with HL-II at 53,000 daltons which was absent in a control blot treated with preimmune serum. Adrenal lipase and authentic hepatic lipase yielded similar peptide maps, confirming the presence of the lipase in adrenal gland. However, incorporation of L-(/sup 35/S)methionine into immunoprecipitable hepatic lipase was not detected in this tissue. In addition, Northern blot analysis showed the presence of hepatic lipase mRNA in liver but not adrenal gland. The presence of hepatic lipase in adrenal gland in the absence of detectable synthesis or messenger suggests that hepatic lipase originates in liver and is transported to this extrahepatic site.

  8. Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

    PubMed

    Abd El-Twab, Sanaa M; Mohamed, Hanaa M; Mahmoud, Ayman M

    2016-06-01

    Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P < 0.001) increase in glycosylated hemoglobin, glucose, homeostasis model of insulin resistance, and pro-inflammatory cytokines. Serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly (P < 0.001) decreased in diabetic rats. Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P < 0.001) down-regulated in testes of diabetic rats, an effect which was significantly increased after administration of taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis. PMID:27089006

  9. Antidepressant dose of taurine increases mRNA expression of GABAA receptor α2 subunit and BDNF in the hippocampus of diabetic rats.

    PubMed

    Caletti, Greice; Almeida, Felipe Borges; Agnes, Grasiela; Nin, Maurício Schüler; Barros, Helena Maria Tannhauser; Gomez, Rosane

    2015-04-15

    Diabetes mellitus is a metabolic disorder associated with higher risk for depression. Diabetic rats present depressive-like behaviors and taurine, one of the most abundant free amino acids in the brain, reverses this depressive behaviors. Because taurine is a GABAA agonist modulator, we hypothesize that its antidepressant effect results from the interaction on this system by changing α2 GABAA receptor subunit expression, beside changes on BDNF mRNA, and memory in diabetic rats. Streptozotocin-diabetic and non-diabetic Wistar rats were daily injected with 100mg/kg of taurine or saline, intraperitoneally, for 30 days. At the end of the experiment, rats were exposed to the novel object recognition memory. Later they were euthanized, the brains were weighed, and the hippocampus was dissected for α2 GABAA subunit and BDNF mRNA expression. Real-time quantitative PCR (qPCR) showed that diabetic rats presented lower α2 GABAA subunit and BDNF mRNA expression than non-diabetic rats and taurine increased both parameters in these sick rats. Taurine also reversed the lower brain weight and improved the short-term memory in diabetic rats. Thus, the taurine antidepressant effect may be explained by interference with the GABA system, in line to its neuroprotective effect showed here by preventing brain weight loss and improving memory in diabetic rats. PMID:25612506

  10. Study on the interaction of plasma protein binding rate between edaravone and taurine in human plasma based on HPLC analysis coupled with ultrafiltration technique.

    PubMed

    Tang, Dao-quan; Li, Yin-jie; Li, Zheng; Bian, Ting-ting; Chen, Kai; Zheng, Xiao-xiao; Yu, Yan-yan; Jiang, Shui-shi

    2015-08-01

    In this work, two high-performance liquid chromatography (HPLC) assays were developed and validated for the independent determination of edaravone and taurine using 3-methyl-1-p-tolyl-5-pyrazolone and L-glutamine as internal standards. In in vitro experiments, human plasma was separately spiked with a mixture of edaravone and taurine, edaravone or taurine alone. Plasma was precipitated with acetonitrile containing 0.1% formic acid. Ultrafiltration was employed to obtain the unbound ingredients of the two drugs. The factors that might influence the ultrafiltration effiency were elaborately optimized. Plasma supernatant and ultrafiltrate containing taurine were derivated with o-phthalaldehyde and ethanethiol in the presence of 40 mmol/L sodium borate buffer (pH 10.2) at room temperature within 1 min. Chromatographic separations were achieved on an InertSustain C18 column (250 × 4.6 mm, 5 µm). Isocratic 50 mmol/L ammonium acetate-acetonitrile and gradient 50 mmol/L sodium acetate (pH 5.3)-methanol were respectively selected as the mobile phase for the determination of edaravone and taurine. All of the validation data including linearity, extraction recovery, precision, accuracy and stability conformed to the requirements. Results showed that there were no significant alterations in the plasma protein binding rate of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible. PMID:25545282

  11. Activation of GABA(A) receptors by taurine and muscimol blocks the neurotoxicity of beta-amyloid in rat hippocampal and cortical neurons.

    PubMed

    Paula-Lima, Andréa C; De Felice, Fernanda G; Brito-Moreira, Jordano; Ferreira, Sérgio T

    2005-12-01

    The beta-amyloid peptide (Abeta) is centrally related to the pathogenesis of Alzheimer's disease (AD) and is potently neurotoxic to central nervous system neurons. The neurotoxicity of Abeta has been partially related to the over activation of glutamatergic transmission and excitotoxicity. Taurine is a naturally occurring beta-amino acid present in the mammalian brain. Due to its safety and tolerability, taurine has been clinically used in humans in the treatment of a number of non-neurological disorders. Here, we show that micromolar doses of taurine block the neurotoxicity of Abeta to rat hippocampal and cortical neurons in culture. Moreover, taurine also rescues central neurons from the excitotoxicity induced by high concentrations of extracellular glutamate. Neuroprotection by taurine is abrogated by picrotoxin, a GABA(A) receptor antagonist. GABA and muscimol, an agonist of the GABA(A) receptor, also block neuronal death induced by Abeta in rat hippocampal and cortical neurons. These results suggest that activation of GABA(A) receptors protects neurons against Abeta toxicity in AD-affected regions of the mammalian brain and that taurine should be investigated as a novel therapeutic tool in the treatment of AD and of other neurological disorders in which excitotoxicity plays a relevant role. PMID:16150468

  12. Pathogenesis of Hepatic Encephalopathy

    PubMed Central

    Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

    2012-01-01

    Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

  13. Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage

    PubMed Central

    Abdel-Moneim, Ashraf M.; Al-Kahtani, Mohammed A.; El-Kersh, Mohamed A.; Al-Omair, Mohammed A.

    2015-01-01

    The present study aims to investigate the hepatoprotective effect of taurine (TAU) alone or in combination with silymarin (SIL) on CCl4-induced liver damage. Twenty five male rats were randomized into 5 groups: normal control (vehicle treated), toxin control (CCl4 treated), CCl4+TAU, CCl4+SIL and CCl4+TAU+SIL. CCl4 provoked significant increases in the levels of hepatic TBARS, NO and NOS compared to control group, but the levels of endogenous antioxidants such as SOD, GPx, GR, GST and GSH were significantly decreased. Serum pro-inflammatory and fibrogenic cytokines including TNF-α, TGF-β1, IL-6, leptin and resistin were increased while the anti-inflammatory (adiponectin) cytokine was decreased in all treated rats. Our results also showed that CCl4 induced an increase in liver injury parameters like serum ALT, AST, ALP, GGT and bilirubin. In addition, a significant increase in liver tissue hydroxyproline (a major component of collagen) was detected in rats exposed to CCl4. Moreover, the concentrations of serum TG, TC, HDL-C, LDL-C, VLDL-C and FFA were significantly increased by CCl4. Both TAU and SIL (i.e., antioxidants) post-treatments were effectively able to relieve most of the above mentioned imbalances. However, the combination therapy was more effective than single applications in reducing TBARS levels, NO production, hydroxyproline content in fibrotic liver and the activity of serum GGT. Combined treatment (but not TAU- or SIL-alone) was also able to effectively prevent CCl4-induced decrease in adiponectin serum levels. Of note, the combined post-treatment with TAU+SIL (but not monotherapy) normalized serum FFA in CCl4-treated rats. The biochemical results were confirmed by histological and ultrastructural changes as compared to CCl4-poisoned rats. Therefore, on the basis of our work, TAU may be used in combination with SIL as an additional adjunct therapy to cure liver diseases such as fibrosis, cirrhosis and viral hepatitis. PMID:26659465

  14. Hepatitis: protecting BMETs & CEs.

    PubMed

    Baker, S A

    1994-01-01

    Hepatitis is the primary occupational hazard for healthcare workers. Not until the 1970s were hepatitis viruses isolated and identified as types A and B. In the late 1970s, hepatitis D was discovered as a major cause of fulminant hepatitis. Soon, it was evident that another type was also at work. Because testing was only available for types A and B, the new category was referred to as non-A, non-B. In the 1980s, scientists identified two more viruses from this non-A, non-B group, namely hepatitis E and hepatitis C. These five types of hepatitis have different modes of transmission. The fecal-to-oral route is the mode of transmission for hepatitis types A and E. But, types B and D are bloodborne pathogens. With the advent of a safe vaccine for hepatitis B, this category is declining. To date, hepatitis C appears to have multiple routes of transmission, with half the cases being posttransfusion. In the United States, 85,000 people per year develop chronic hepatitis C, which ultimately leads to severe liver damage. This paper addresses each of the five viruses that have been grouped by routes of transmission, prevention techniques for BMETs and CEs, and statistics of reported cases to the Centers for Disease Control and Prevention (CDCP) over the last 20 years. PMID:10139739

  15. Toluene induces rapid and reversible rise of hippocampal glutamate and taurine neurotransmitter levels in mice.

    PubMed

    Win-Shwe, Tin-Tin; Mitsushima, D; Nakajima, D; Ahmed, S; Yamamoto, S; Tsukahara, S; Kakeyama, M; Goto, S; Fujimaki, H

    2007-01-10

    Toluene, a widely used aromatic organic solvent, has been well characterized as a neurotoxic chemical. Although the neurobehavioral effects of toluene have been studied substantially, the mechanisms involved are not clearly understood. Hippocampus, which is one of the limbic areas of brain associated with neuronal plasticity, and learning and memory functions, may be a principal target of toluene. In the present study, to establish a mouse model for investigating the effects of acute toluene exposure on the amino acid neurotransmitter levels in the hippocampus, in vivo microdialysis study was performed in freely moving mice after a single intraperitoneal administration of toluene (150 and 300 mg/kg). Amino acid neurotransmitters in microdialysates were measured by a high performance liquid chromatography system. The extracellular levels of glutamate and taurine were rapidly and reversibly increased within 30 min after the toluene administration in a dose-dependent manner and returned to the basal level by 1h. Conversely, the extracellular level of glycine and GABA were stable, and no significant change was observed after the toluene administration. To further investigate the brain toluene level in the hippocampus of toluene-administered mice, we used a solid-phase microextraction (SPME) method and examined the time course changes of toluene in the hippocampus of living mice. The brain toluene level reached the peak at 30 min after injection and returned to the basal level after 2h. In the present study, we observed the relationship between brain toluene levels and amino acid neurotransmitter glutamate and taurine levels in the hippocampus. Therefore, we suggest that toluene may mediate its action through the glutamatergic and taurinergic neurotransmission in the hippocampus of freely moving mice. PMID:17145141

  16. Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur

    PubMed Central

    Ueki, Iori

    2010-01-01

    Synthesis of cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homocysteine degradation, with cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homocysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H2S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by alternate reactions catalyzed by cystathionine β-synthase and cystathionine γ-lyase. Cysteine is also catabolized by pathways that require the initial oxidation of the cysteine thiol by cysteine dioxygenase to form cysteinesulfinate. The oxidative pathway leads to production of taurine and sulfate in a ratio of approximately 2:1. Relative metabolism of cysteine by desulfuration versus oxidative pathways is influenced by cysteine dioxygenase activity, which is low in animals fed low-protein diets and high in animals fed excess sulfur amino acids. Thus, desulfuration reactions dominate when cysteine is deficient, whereas oxidative catabolism dominates when cysteine is in excess. In rats consuming a diet with an adequate level of sulfur amino acids, about two thirds of cysteine catabolism occurs by oxidative pathways and one third by desulfuration pathways. Cysteine dioxygenase is robustly regulated in response to cysteine availability and may function to provide a pathway to siphon cysteine to less toxic metabolites than those produced by cysteine desulfuration reactions. PMID:20162368

  17. Identification of novel thermostable taurine-pyruvate transaminase from Geobacillus thermodenitrificans for chiral amine synthesis.

    PubMed

    Chen, Yujie; Yi, Dong; Jiang, Shuiqin; Wei, Dongzhi

    2016-04-01

    ω-Transaminases (ω-TAs) are one of the most popular candidate enzymes in the biosynthesis of chiral amines. Determination of yet unidentified ω-TAs is important to broaden their potential for synthetic application. Taurine-pyruvate TA (TPTA, EC 2.6.1.77) is an ω-TA belonging to class III of TAs. In this study, we cloned a novel thermostable TPTA from Geobacillus thermodenitrificans (TPTAgth) and overexpressed it in Escherichia coli. The enzyme showed the highest activity at pH 9.0 and 65 °C, with remarkable thermostability and tolerance toward organic solvents. Its K M and v max values for taurine were 5.3 mM and 0.28 μmol s(-1) mg(-1), respectively. Determination of substrate tolerance indicated its broad donor and acceptor ranges for unnatural substrates. Notably, the enzyme showed relatively good activity toward ketoses, suggesting its potential for catalyzing the asymmetric synthesis of chiral amino alcohols. The active site of TPTAgth was identified by performing protein sequence alignment, three-dimensional structure simulation, and coenzyme pyridoxamine phosphate docking. The protein sequence and structure of TPTAgth were similar to those of TAs belonging to the 3N5M subfamily. Its active site was found to be its special large pocket and substrate tunnel. In addition, TPTAgth showed a unique mechanism of sulfonate/α-carboxylate recognition contributed by Arg163 and Gln160. We also determined the protein sequence fingerprint of TPTAs in the 3N5M subfamily, which involved Arg163 and Gln160 and seven additional residues from 413 to 419 and lacked Phe/Tyr22, Phe85, and Arg409. PMID:26577674

  18. Risk assessment for the amino acids taurine, L-glutamine and L-arginine.

    PubMed

    Shao, Andrew; Hathcock, John N

    2008-04-01

    Taurine, glutamine and arginine are examples of amino acids which have become increasingly popular as ingredients in dietary supplements and functional foods and beverages. Animal and human clinical research suggests that oral supplementation of these amino acids provides additional health and/or performance benefits beyond those observed from normal intake of dietary protein. The increased consumer awareness and use of these amino acids as ingredients in dietary supplements and functional foods warrant a comprehensive review of their safety through quantitative risk assessment, and identification of a potential safe upper level of intake. The absence of a systematic pattern of adverse effects in humans in response to orally administered taurine (Tau), l-glutamine (Gln) and l-arginine (Arg) precluded the selection of a no observed adverse effect level (NOAEL) or lowest observed adverse effect level (LOAEL). Therefore, by definition, the usual approach to risk assessment for identification of a tolerable upper level of intake (UL) could not be used. Instead, the newer method described as the Observed Safe Level (OSL) or Highest Observed Intake (HOI) was utilized. The OSL risk assessments indicate that based on the available published human clinical trial data, the evidence for the absence of adverse effects is strong for Tau at supplemental intakes up to 3 g/d, Gln at intakes up to 14 g/d and Arg at intakes up to 20 g/d, and these levels are identified as the respective OSLs for normal healthy adults. Although much higher levels of each of these amino acids have been tested without adverse effects and may be safe, the data for intakes above these levels are not sufficient for a confident conclusion of long-term safety, and therefore these values are not selected as the OSLs. PMID:18325648

  19. Alcoholic hepatitis.

    PubMed

    Damgaard Sandahl, Thomas

    2014-10-01

    Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (< 84 days after diagnosis), patients with AH were likely to die from liver-related events and infections. In the long-term (≥ 84 days after diagnosis), those who developed cirrhosis mainly died from liver-related causes, and

  20. Hepatic encephalopathy: a review.

    PubMed

    Lizardi-Cervera, Javier; Almeda, Paloma; Guevara, Luis; Uribe, Misael

    2003-01-01

    Hepatic encephalopathy (HE) is a complication that presents in as many as 28% of patients with cirrhosis, and reported up to ten years after the diagnosis of cirrhosis. Commonly, it is observed in patients with severe hepatic failure and is characterized by neuropsychiatric manifestations that can range in severity from a mild alteration in mental state to a coma; additionally, some neuromuscular symptoms can be observed. This complication of either acute or chronic hepatic disease is the result of a diminished hepatic reservoir and inability to detoxify some toxins that originate in the bowel. Today, the role of astrocytes, specifically the Alzheimer type II cells, is known to be very important in the pathogenesis of the hepatic encephalopathy, and will be reviewed later. In conclusion, the objectives of this review are: To understand the pathogenesis of hepatic encephalopathy, To recognize the precipitating factors, as well as preventive measures for the development of the hepatic encephalopathy, To describe the new classification of hepatic encephalopathy and its clinical implications, To recognize the clinical manifestations and stages of the disease, To understand the main diagnostic tests used to detect the hepatic encephalopathy, To describe the main therapeutic treatments of hepatic encephalopathy. PMID:15115963

  1. Isolation and Total Synthesis of Stolonines A-C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera.

    PubMed

    Tran, Trong D; Pham, Ngoc B; Ekins, Merrick; Hooper, John N A; Quinn, Ronald J

    2015-07-01

    Cnemidocarpa stolonifera is an underexplored marine tunicate that only occurs on the tropical to subtropical East Coast of Australia, with only two pyridoacridine compounds reported previously. Qualitative analysis of the lead-like enhanced fractions of C. stolonifera by LC-MS dual electrospray ionization coupled with PDA and ELSD detectors led to the identification of three new natural products, stolonines A-C (1-3), belonging to the taurine amide structure class. Structures of the new compounds were determined by NMR and MS analyses and later verified by total synthesis. This is the first time that the conjugates of taurine with 3-indoleglyoxylic acid, quinoline-2-carboxylic acid and β-carboline-3-carboxylic acid present in stolonines A-C (1-3), respectively, have been reported. An immunofluorescence assay on PC3 cells indicated that compounds 1 and 3 increased cell size, induced mitochondrial texture elongation, and caused apoptosis in PC3 cells. PMID:26204949

  2. Properties of Taurine Release in Glucose-Free Media in Hippocampal Slices from Developing and Adult Mice

    PubMed Central

    Oja, Simo S.; Saransaari, Pirjo

    2015-01-01

    The release of preloaded [3H]taurine from hippocampal slices from developing 7-day-old and young adult 3-month-old mice was studied in a superfusion system in the absence of glucose. These hypoglycemic conditions enhanced the release at both ages, the effect being markedly greater in developing mice. A depolarizing K+ concentration accentuated the release, which indicates that it was partially mediated by exocytosis. The anion channel blockers were inhibitory, witnessing the contribution of ion channels. NO-generating agents fomented the release as a sign of the participation of excitatory amino acid receptors. The other second messenger systems were apparently less efficient. The much greater taurine release could be a reason for the well-known greater tolerance of developing nervous tissue to lack of glucose. PMID:26347028

  3. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study

    PubMed Central

    Yablonsky-Alter, Elena; Agovic, Mervan S.; Gashi, Eleonora; Lidsky, Theodore I.; Friedman, Eitan; Banerjee, Shailesh P.

    2009-01-01

    Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly increased the release of glutamate, which may cause neurotoxicity. Simultaneously, cocaine challenge after withdrawal also significantly increased the release of taurine, which counteracts glutamate-mediated excitotoxicity and possibly cell death. Thus, the mammalian brain has an endogenous self-protective mechanism against cocaine-mediated neurotoxicity and potentially addiction. PMID:19166917

  4. Isolation and Total Synthesis of Stolonines A–C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera

    PubMed Central

    Tran, Trong D.; Pham, Ngoc B.; Ekins, Merrick; Hooper, John N. A.; Quinn, Ronald J.

    2015-01-01

    Cnemidocarpa stolonifera is an underexplored marine tunicate that only occurs on the tropical to subtropical East Coast of Australia, with only two pyridoacridine compounds reported previously. Qualitative analysis of the lead-like enhanced fractions of C. stolonifera by LC-MS dual electrospray ionization coupled with PDA and ELSD detectors led to the identification of three new natural products, stolonines A–C (1–3), belonging to the taurine amide structure class. Structures of the new compounds were determined by NMR and MS analyses and later verified by total synthesis. This is the first time that the conjugates of taurine with 3-indoleglyoxylic acid, quinoline-2-carboxylic acid and β-carboline-3-carboxylic acid present in stolonines A–C (1–3), respectively, have been reported. An immunofluorescence assay on PC3 cells indicated that compounds 1 and 3 increased cell size, induced mitochondrial texture elongation, and caused apoptosis in PC3 cells. PMID:26204949

  5. Feature Hepatitis: Hepatitis Can Strike Anyone

    MedlinePlus

    ... please turn Javascript on. From Hollywood's "Walk of Stars" to Main Street, USA, people from all walks ... that includes many well-known names: Legendary television star Larry Hagman was diagnosed with advanced hepatitis C ...

  6. A taurine-supplemented vegan diet may blunt the contribution of neutrophil activation to acute coronary events.

    PubMed

    McCarty, Mark F

    2004-01-01

    Neutrophils are activated in the coronary circulation during acute coronary events (unstable angina and myocardial infarction), often prior to the onset of ischemic damage. Moreover, neutrophils infiltrate coronary plaque in these circumstances, and may contribute to the rupture or erosion of this plaque, triggering thrombosis. Activated neutrophils secrete proteolytic enzymes in latent forms which are activated by the hypochlorous acid (HOCl) generated by myeloperoxidase. These phenomena may help to explain why an elevated white cell count has been found to be an independent coronary risk factor. Low-fat vegan diets can decrease circulating leukocytes--neutrophils and monocytes--possibly owing to down-regulation of systemic IGF-I activity. Thus, a relative neutropenia may contribute to the coronary protection afforded by such diets. However, vegetarian diets are devoid of taurine - the physiological antagonist of HOCl--and tissue levels of this nutrient are relatively low in vegetarians. Taurine has anti-atherosclerotic activity in animal models, possibly reflecting a role for macrophage-derived myeloperoxidase in the atherogenic process. Taurine also has platelet-stabilizing and anti-hypertensive effects that presumably could reduce coronary risk. Thus, it is proposed that a taurine-supplemented low-fat vegan diet represents a rational strategy for diminishing the contribution of activated neutrophils to acute coronary events; moreover, such a regimen would work in a number of other complementary ways to promote cardiovascular health. Moderate alcohol consumption, the well-tolerated drug pentoxifylline, and 5-lipoxygenase inhibitors--zileuton, boswellic acids, fish oil--may also have potential in this regard. PMID:15288360

  7. Taurine protects against As2O3-induced autophagy in pancreas of rat offsprings through Nrf2/Trx pathway.

    PubMed

    Bai, Jie; Yao, Xiaofeng; Jiang, Liping; Qiu, Tianming; Liu, Shuang; Qi, Baoxu; Zheng, Yue; Kong, Yuan; Yang, Guang; Chen, Min; Liu, Xiaofang; Sun, Xiance

    2016-04-01

    Arsenic was increasingly to blame as a risk factor for type 2 diabetes mellitus. In our previous study, we had found iAs stimulated autophagic flux and caused autophagic cell death through ROS pathway in INS-1 cells. Since NF-E2-related factor 2 (Nrf2) and the thioredoxin (Trx) system was a crucial line of defense against ROS, we investigated whether Nrf2/Trx pathway contributed to As2O3-stimulated autophagy and the role of taurine in this study. After treatment with 2 mg/kg BW-8 mg/kg BW As2O3 for 57 d, the expression of Nrf2 protein was decreased significantly in offsprings' pancreas. The expression of Trx gene was decreased significantly in pancreas subsequently. Finally, the generation of reactive oxygen species stimulated autophagy in arsenic-treated pancreas. Taurine could reverse arsenic-inhibited Nrf2 and Trx and inhibit autophagy. In short, inhibition of Nrf2/Trx pathway might play an important role in the pathogenesis of arsenic-related diabetes. Taurine could serve as nutrition supplementation against arsenic-related diabetes in high arsenic exposure area. PMID:26775255

  8. Effects of in vitro ozone exposure on peroxidative damage, membrane leakage, and taurine content of rat alveolar macrophages

    SciTech Connect

    Banks, M.A.; Porter, D.W.; Martin, W.G.; Castranova, V. )

    1990-08-01

    Rat alveolar macrophages (AM) were isolated by pulmonary lavage, allowed to adhere to a tissue culture flask, and then exposed to 0.45 +/- 0.05 ppm ozone. After exposures ranging from 0 to 60 min, the medium was decanted and cells were harvested. Cells were assayed for oxidant damage and media analyzed for leakage of intracellular components. Increasing length of exposure to ozone resulted in a decreased number of adherent AM and decreased cell viability. Resting and zymosan-stimulated chemiluminescence increased immediately after ozone exposure and reached a maximum at 15-30 min, then declined to initial levels after 60 min of ozone exposure. Lipid peroxidation and leakage of protein and K+ ions increased with increasing length of exposure to ozone, while leakage of reduced and oxidized glutathione increased through 30 min, then declined (reduced) or leveled off (oxidized). Activity of the Na+/K+ ATPase decreased with time while intracellular taurine concentration exhibited an initial rise, peaked at 30 min, and then returned to the untreated level. Leakage of taurine into the medium increased with time of exposure, suggesting that exposure of AM to ozone results in a shift from bound to free intracellular taurine. These data indicate that in vitro exposure of AM to ozone results in a time-dependent alteration of cell function, membrane integrity, and viability.

  9. Effect of pimobendan on the clinical outcome and survival of cats with non-taurine responsive dilated cardiomyopathy.

    PubMed

    Hambrook, Lydia E; Bennett, Peter F

    2012-04-01

    This retrospective study was designed to assess the effect of pimobendan on the median survival time (MST) of cats with non-taurine responsive dilated cardiomyopathy (DCM). Thirty-two client-owned cats with a left ventricular internal dimension at end systole (LVIDs) >14 mm, a fractional shortening (FS) <28% and a lack of response to taurine therapy were included over a 9-year period (2001-2010). These cats were divided into pimobendan (n=16) and non-pimobendan (n=16) treatment groups. All cats received standard treatment with frusemide, taurine and benazepril or enalapril. Nine cats in the non-pimobendan group also received digoxin. The MST of the pimobendan group (49 days; range 1 to >502 days) was four times that of the non-pimobendan group (12 days; 1 to 244 days). The difference in survival between the two groups was statistically significant (P = 0.048). Hypothermia and FS <20% were associated with a poor prognosis. No adverse effects to pimobendan were noted. PMID:22412159

  10. Microsatellite DNA Variation and the Evolution, Domestication and Phylogeography of Taurine and Zebu Cattle (Bos Taurus and Bos Indicus)

    PubMed Central

    MacHugh, D. E.; Shriver, M. D.; Loftus, R. T.; Cunningham, P.; Bradley, D. G.

    1997-01-01

    Genetic variation at 20 microsatellite loci was surveyed to determine the evolutionary relationships and molecular biogeography of 20 different cattle populations from Africa, Europe and Asia. Phylogenetic reconstruction and multivariate analysis highlighted a marked distinction between humpless (taurine) and humped (zebu) cattle, providing strong support for a separate origin for domesticated zebu cattle. A molecular clock calculation using bison (Bison sp.) as an outgroup gave an estimated divergence time between the two subspecies of 610,000-850,000 years. Substantial differences in the distribution of alleles at 10 of these loci were observed between zebu and taurine cattle. These markers subsequently proved very useful for investigations of gene flow and admixture in African populations. When these data were considered in conjunction with previous mitochondrial and Y chromosomal studies, a distinctive male-mediated pattern of zebu genetic introgression was revealed. The introgression of zebu-specific alleles in African cattle afforded a high resolution perspective on the hybrid nature of African cattle populations and also suggested that certain West African populations of valuable disease-tolerant taurine cattle are under threat of genetic absorption by migrating zebu herds. PMID:9215909

  11. Low taurine, gamma-aminobutyric acid and carnosine levels in plasma of diabetic pregnant rats: consequences for the offspring.

    PubMed

    Aerts, L; Van Assche, F A

    2001-01-01

    Gestational diabetes compromises fetal development and induces a diabetogenic effect in the offspring, including the development of gestational diabetes and the transmission of the effect to the next generation. Changes are not limited to glucose and insulin metabolism, and appear to be modulated by alterations at the hypothalamo-hypophyseal axis. In the present work, serum concentrations are given for the non-protein amino-acids taurine and gamma-aminobutyric acid (GABA), both neurotransmitters essential for normal brain development, and for the endogenous neuroprotector carnosine, a known anti-oxydans. Taurine levels are significantly below normal values in mildly diabetic mothers, in their fetal and adult offspring, virgin and pregnant, and in the fetuses of these pregnant offspring. GABA and carnosine levels are at the limit of detection in the diabetic mothers and their offspring at every stage. It is concluded that the low taurine, GABA and carnosine levels in diabetic mothers and their fetuses might compromise the normal structural and functional development of the fetal brain. When adult, these offspring present a deficiency of the circulating levels of these neurotransmitters involved in the hypothalamo-hypophyseal regulation of insulin secretion. This might contribute to the development of impaired glucose tolerance and gestational diabetes, thereby transmitting the effect to the next generation. PMID:11234622

  12. Differential increase in taurine levels by low-dose ethanol in the dorsal and ventral striatum revealed by microdialysis with on-line capillary electrophoresis.

    PubMed

    Smith, A; Watson, C J; Frantz, K J; Eppler, B; Kennedy, R T; Peris, J

    2004-07-01

    Ethanol increases taurine efflux in the nucleus accumbens or ventral striatum (VS), a dopaminergic terminal region involved in positive reinforcement. However, this has been found only at ethanol doses above 1 g/kg intraperitoneally, which is higher than what most rats will self-administer. We used a sensitive on-line assay of microdialysate content to test whether lower doses of ethanol selectively increase taurine efflux in VS as opposed to other dopaminergic regions not involved in reinforcement (e.g., dorsal striatum; DS). Adult male rats with microdialysis probes in VS or DS were injected with ethanol (0, 0.5, 1, and 2 g/kg intraperitoneally), and the amino acid content of the dialysate was measured every 11 sec using capillary electrophoresis and laser-induced fluorescence detection. In VS, 0.5 g/kg ethanol significantly increased taurine levels by 20% for 10 min. A similar increase was seen after 1 g/kg ethanol, which lasted for about 20 min after injection. A two-phased taurine efflux was observed with the 2.0 g/kg dose, where taurine was increased by 2-fold after 5 min but it remained elevated by 30% for at least 60 min. In contrast, DS exhibited much smaller dose-related increases in taurine. Glycine, glutamate, serine, and gamma-aminobutyric acid were not systematically affected by lower doses of ethanol; however, 2 g/kg slowly decreased these amino acids in both brain regions during the hour after injection. These data implicate a possible role of taurine in the mechanism of action of ethanol in the VS. The high sensitivity and time resolution afforded by capillary electrophoresis and laser-induced fluorescence detection will be useful for detecting subtle changes of neuronally active amino acids levels due to low doses of ethanol. PMID:15252289

  13. Preventing hepatitis B or C

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000401.htm Preventing hepatitis B or C To use the sharing features on this page, please enable JavaScript. Hepatitis B and hepatitis C infections cause irritation and ...

  14. Hepatitis B in Pregnancy.

    PubMed

    Tran, Tram T

    2016-06-01

    Chronic hepatitis B virus (HBV) infection is estimated to affect >350 million people worldwide and represents a significant cause of morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Mother-to-child transmission (MTCT) of HBV remains an important source of incident cases of HBV. Current barriers to eradication of incident HBV infections via MTCT include underutilization of immunoprophylaxis with hepatitis B vaccination and hepatitis B immune globulin in certain endemic regions as well as failure of immunoprophylaxis. PMID:27190321

  15. Hepatitis C: Information on Testing and Diagnosis

    MedlinePlus

    HEPATITIS C Information on Testing & Diagnosis What is Hepatitis C? Hepatitis C is a serious liver disease that results from infection with the Hepatitis C virus. Hepatitis C has been called a silent ...

  16. [Treatment for hepatic osteodystrophy].

    PubMed

    Kaji, Hiroshi

    2015-11-01

    Chronic liver diseases, including liver cirrhosis, are caused by various pathogenesis, such as viral hepatitis, primary biliary cirrhosis, autoimmune hepatitis and steatohepatitis. There have not been enough clinical evidence about the treatment of hepatic osteodystrophy at the present time. Several reports suggested that bisphosphonates, such as alendronate, are effective for an increase in bone mineral density in patients with chronic liver disease. Vitamin D treatment might be useful for the frequent prevalence of vitamin D deficiency in the pathogenesis of hepatic oseodystrophy. The use of estrogens will be limited for the risk of liver dysfunction and hepatocellular carcinoma. PMID:26503875

  17. Erythropoietic and hepatic porphyrias.

    PubMed

    Gross, U; Hoffmann, G F; Doss, M O

    2000-11-01

    Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10%, of patients. Acute hepatic porphyrias (delta-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological-psychiatric and cardiovascular manifestations requiring early diagnosis to avoid life-threatening complications. Acute hepatic porphyrias are pharmacogenetic and molecular regulatory diseases (without porphyrin accumulation) mainly induced by drugs, sex hormones, fasting or alcohol. The disease process depends on the derepression of hepatic delta-aminolaevulinic acid synthase following haem depletion. In contrast to the acute porphyrias, nonacute, chronic hepatic porphyrias such as porphyria cutanea tarda are porphyrin accumulation disorders leading to cutaneous symptoms associated with liver disease, especially caused by alcohol or viral hepatitis. Alcohol, oestrogens, haemodialysis, hepatitis C and AIDS are triggering factors. Porphyria cutanea tarda is the most common porphyria, followed by acute intermittent porphyria and erythropoietic protoporphyria. The molecular genetics of the porphyrias is very heterogenous. Nearly every family has its own mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life. Thus, the recognition of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias. Consequently, haem precursors are synthesized in excess. The increased

  18. AB096. Taurine supplementation improves erectile function in rats with streptozotocin-induced type 1 diabetes via amelioration of penile fibrosis and endothelial dysfunction

    PubMed Central

    Ruan, Yajun; Li, Mingchao; Wang, Tao; Yang, Jun; Rao, Ke; Wang, Shaogang; Yang, Weimin; Liu, Jihong; Ye, Zhangqun

    2016-01-01

    Objective For patients with diabetes, erectile dysfunction (ED) is common and greatly affects quality of life. However, these patients often exhibit a poor response to first-line oral phosphodiesterase type 5 inhibitors. The aim of this study was to investigate whether taurine, a sulfur-containing amino acid, affects diabetic ED (DED). Methods Type 1 diabetes mellitus was induced in male rats using streptozotocin. After 12 weeks, an apomorphine test was conducted to confirm DED. Only rats with DED were administered taurine or vehicle for four weeks. Age-matched nondiabetic rats were administered saline intraperitoneally for four weeks. Erectile function was evaluated by electrical stimulation of the cavernous nerve. Histologic and molecular alterations of the corpus cavernosum also were analyzed. Results Erectile function was significantly reduced in the diabetic rats compared with in the nondiabetic rats, and was ameliorated in the diabetic rats treated with taurine. The corpus cavernosum of the rats with DED exhibited severe fibrosis and decreased smooth muscle content. Deposition of extracellular matrix proteins was increased in the diabetic rats, while expression of endothelial nitric oxide synthase/cyclic guanosine monophosphate/nitric oxide pathway–related proteins was reduced. Taurine supplementation restored erectile response as well as histologic and molecular alterations. Conclusions Taurine supplementation improves erectile function in rats with DED probably by potential antifibrotic activity. This finding provides evidence for a potential new therapy for DED.

  19. Hepatitis (For Parents)

    MedlinePlus

    ... people at risk for contracting hepatitis. But frequent hand washing and good hygiene practices can reduce this risk. All kids in ... to prevent viral hepatitis you should: Follow good hygiene and avoid crowded, ... their hands thoroughly after using the toilet and before eating. ...

  20. Hepatitis and activity

    PubMed Central

    Krikler, Dennis M.

    1971-01-01

    The effects of physical activity during an attack of infectious hepatitis are discussed. There is no evidence that activity during convalescence produces any ill-effects. On the other hand, strenuous physical activity in the acute stage may be dangerous, possibly because hepatic blood-flow is reduced. PMID:5560143

  1. [Update chronic viral hepatitis].

    PubMed

    Ziegenhagen, D J

    2016-03-01

    More than 500,000 people in Germany have chronic viral hepatitis. The interferon-based treatments formerly used in hepatitis B have been widely replaced by life-long oral medication with nucleoside or nucleotide analogues. Treatment for chronic hepatitis C has been improved substantially by the development of new and very expensive drug combinations. Up to 90% of patients can now be cured with certainty, and one to two years after successful treatment there is no relevant risk of recurrence. These individuals expect to receive insurance cover under appropriate conditions. Vaccination programmes are very efficient at decreasing the incidence of hepatitis B, but no vaccine against hepatitis C is likely to become available in the next decade. PMID:27111951

  2. Update on Alcoholic Hepatitis

    PubMed Central

    Torok, Natalie J.

    2015-01-01

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%–50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies. PMID:26540078

  3. Hepatitis E in Transplantation.

    PubMed

    Marion, Olivier; Abravanel, Florence; Lhomme, Sebastien; Izopet, Jacques; Kamar, Nassim

    2016-03-01

    Hepatitis E virus (HEV) has a worldwide distribution and is known to cause acute and fulminant hepatitis. However, over the last few years, it has been shown to also cause chronic hepatitis and cirrhosis in immunosuppressed patients, especially solid-organ-transplant patients. In immunocompetent and immunosuppressed patients, HEV is also associated with extra-hepatic manifestations, such as neurological symptoms and kidney injury. Unfortunately, a diagnostic assay for HEV infection is still not available in all countries. Reduction of immunosuppression is the first-line therapeutic option for organ-transplant patients with chronic hepatitis. In addition, ribavirin is highly efficient at treating chronic HEV infection. In this comprehensive review, we summarize the current knowledge regarding HEV diagnosis, its natural history, clinical manifestations, and treatments in patients with a solid-organ transplant. PMID:26838163

  4. Does taurine deficiency cause metabolic bone disease and rickets in polar bear cubs raised in captivity?

    PubMed

    Chesney, Russell W; Hedberg, Gail E; Rogers, Quinton R; Dierenfeld, Ellen S; Hollis, Bruce E; Derocher, Andrew; Andersen, Magnus

    2009-01-01

    Rickets and fractures have been reported in captive polar bears. Taurine (TAU) is key for the conjugation of ursodeoxycholic acid (UDCA), a bile acid unique to bears. Since TAU-conjugated UDCA optimizes fat and fat-soluble vitamin absorption, we asked if TAU deficiency could cause vitamin D malabsorption and lead to metabolic bone disease in captive polar bears. We measured TAU levels in plasma (P) and whole blood (WB) from captive and free-ranging cubs and adults, and vitamin D3 and TAU concentrations in milk samples from lactating sows. Plasma and WB TAU levels were significantly higher in cubs vs captive and free-ranging adult bears. Vitamin D in polar bear milk was 649.2 +/- 569.2 IU/L, similar to that found in formula. The amount of TAU in polar bear milk is 3166.4 +/- 771 nmol/ml, 26-fold higher than in formula. Levels of vitamin D in bear milk and formula as well as in plasma do not indicate classical nutritional vitamin D deficiency. Higher dietary intake of TAU by free-ranging cubs may influence bile acid conjugation and improve vitamin D absorption. PMID:19239163

  5. Accurate analysis of taurine, anserine, carnosine and free amino acids in a cattle muscle biopsy sample.

    PubMed

    Imanari, Mai; Higuchi, Mikito; Shiba, Nobuya; Watanabe, Akira

    2010-06-01

    We have established an analysis method for some free amino acids (FAAs), as well as taurine (Tau), anserine (Ans) and carnosine (Car), in a fresh biopsy sample from cattle muscle. A series of model biopsy samples, corresponding to the mixtures of lean meat, fat and connective tissue, was prepared and showed high correlation coefficients between the compound concentration and the 3-methylhistidine (3-MeHis) content derived from hydrolysis of the biopsy sample (r = 0.74-0.95, P < 0.01). Interference from blood contamination could not be neglected, because the concentration of some FAAs in blood was comparable to that in muscle. However, it was possible to control the contamination of Tau, Ans, Car, glutamic acid, glutamine, asparatic acid and alanine to less than 5.0% when the blood contamination was controlled to less than 23%.These results suggest the necessity of measuring 3-MeHis as an index of lean meat and hemoglobin as an index of blood contamination when compounds in muscle biopsy samples are evaluated. We have carried out a series of these analyses using one biopsy sample and reveal differences in Tau, Ans, Car and some FAAs in beef muscle after different feeding regimes. PMID:20597895

  6. Inorganic Nanoparticle as a Carrier for Hepatitis B Viral Capsids

    NASA Astrophysics Data System (ADS)

    Dekhtyar, Yu.; Romanova, M.; Kachanovska, A.; Skrastiņa, D.; Reinhofa, R.; Pumpens, P.; Patmalnieks, A.

    Virus like particles (VLP) are used to transport immune response-modulating agents to target cells to treat them. In order to deliver a high concentration of VLP to the cell, a number of VLP can be attached to a nanoparticle to be used as a nanolorry. In this study, SiO2 nanoparticles were attached to Hepatitis B VLP. Spectrophotometry measurements, electron, and fluorescent microscopy evidence showed that the SiO2 - Hepatitis B VLP complexes were formed.

  7. Role of Adaptor Protein Toll-Like Interleukin Domain Containing Adaptor Inducing Interferon β in Toll-Like Receptor 3- and 4-Mediated Regulation of Hepatic Drug Metabolizing Enzyme and Transporter Genes.

    PubMed

    Shah, Pranav; Omoluabi, Ozozoma; Moorthy, Bhagavatula; Ghose, Romi

    2016-01-01

    The expressions and activities of hepatic drug-metabolizing enzymes and transporters (DMETs) are altered during infection and inflammation. Inflammatory responses in the liver are mediated primarily by Toll-like receptor (TLR)-signaling, which involves recruitment of Toll/interleukin (IL)-1 receptor (TIR) domain containing adaptor protein (TIRAP) and TIR domain containing adaptor inducing interferon (IFN)-β (TRIF) that eventually leads to induction of proinflammatory cytokines and mitogen-activated protein kinases (MAPKs). Lipopolysaccharide (LPS) activates the Gram-negative bacterial receptor TLR4 and polyinosinic:polycytidylic acid (polyI:C) activates the viral receptor TLR3. TLR4 signaling involves TIRAP and TRIF, whereas TRIF is the only adaptor protein involved in the TLR3 pathway. We have shown previously that LPS-mediated downregulation of DMETs is independent of TIRAP. To determine the role of TRIF, we treated TRIF(+/+) and TRIF(-/-) mice with LPS or polyI:C. LPS downregulated (∼40%-60%) Cyp3a11, Cyp2a4, Ugt1a1, Mrp2 mRNA levels, whereas polyI:C downregulated (∼30%-60%) Cyp3a11, Cyp2a4, Cyp1a2, Cyp2b10, Ugt1a1, Mrp2, and Mrp3 mRNA levels in TRIF(+/+) mice. This downregulation was not attenuated in TRIF(-/-) mice. Induction of cytokines by LPS was observed in both TRIF(+/+) and TRIF(-/-) mice. Cytokine induction was delayed in polyI:C-treated TRIF(-/-) mice, indicating that multiple mechanisms mediating polyI:C signaling exist. To assess the role of MAPKs, primary hepatocytes were pretreated with specific inhibitors before treatment with LPS/polyI:C. We found that only the c-jun-N-terminal kinase (JNK) inhibitor attenuated the down-regulation of DMETs. These results show that TRIF-independent pathways can be involved in the downregulation of DMETs through TLR4 and 3. JNK-dependent mechanisms likely mediate this downregulation. PMID:26470915

  8. Hepatitis C virus. A review.

    PubMed Central

    Tang, E.

    1991-01-01

    Hepatitis C virus has been shown to be responsible for most cases of posttransfusion hepatitis, as well as for sporadic non-A, non-B viral hepatitis. Hepatitis C virus has also been implicated in the development of primary hepatocellular carcinoma, autoimmune hepatitis, and fulminant viral hepatitis. Although the role of the parenteral transmission of hepatitis C virus is well established, its route of transmission in cases of sporadic infection remains unclear. Sexual transmission is suspected but not confirmed. Recent work regarding treatment has shown interferon alfa to be effective, but the discontinuation of therapy is associated with a 50% relapse rate. PMID:1656611

  9. Amodiaquine-induced toxicity in isolated rat hepatocytes and the cytoprotective effects of taurine and/or N-acetyl cysteine.

    PubMed

    Heidari, R; Babaei, H; Eghbal, M A

    2014-01-01

    Amodiaquine is an antimalarial drug used in the prophylaxis and treatment of this disease. However, hepatotoxicity as a life-threatening adverse effect is associated with its clinical use. We evaluated amodiaquine-induced toxicity in isolated rat hepatocytes as an in vitro model for studying drug-induced hepatotoxicity. This study attempts to investigate the protective effects of taurine and N-acetyl cysteine against the cytotoxicity induced by amodiaquine. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. This technique is based on liver perfusion with collagenase after removal of calcium ion (Ca(2+)) with a chelator (ethylene glycol tetraacetic acid (EGTA) 0.5 mM). Cells were treated with different concentrations of amodiaquine, taurine and N-acetyl cysteine. Cell death, protein carbonylation, reactive oxygen species formation, lipid peroxidation, and mitochondrial depolarization were assessed as toxicity markers. Amodiaquine cytotoxic mechanism involved protein carbonylation as well as reactive oxygen species formation and lipid peroxidation. In addition, mitochondria seem to be a target for amodiaquine to induce cellular damage. Administration of taurine (200 μM) and/or N-acetyl cysteine (200 μM) reduced oxidative stress, lipid peroxidation and protein carbonylation caused by amodiaquine. Furthermore, amodiaquine-induced mitochondrial injury was significantly mitigated by taurine and/or N-acetyl cysteine. In glutathione-depleted cells, only N-acetyl cysteine protected hepatocytes against amodiaquine, and taurine showed no protective properties in this situation. Taurine and N-acetyl cysteine protect hepatocytes against amodiaquine probably via their antioxidant properties and counteracting oxidative stress. PMID:25657778

  10. A Comparison of Phenotypic Traits Related to Trypanotolerance in Five West African Cattle Breeds Highlights the Value of Shorthorn Taurine Breeds

    PubMed Central

    Berthier, David; Peylhard, Moana; Dayo, Guiguigbaza-Kossigan; Flori, Laurence; Sylla, Souleymane; Bolly, Seydou; Sakande, Hassane; Chantal, Isabelle; Thevenon, Sophie

    2015-01-01

    Background Animal African Trypanosomosis particularly affects cattle and dramatically impairs livestock development in sub-Saharan Africa. African Zebu (AFZ) or European taurine breeds usually die of the disease in the absence of treatment, whereas West African taurine breeds (AFT), considered trypanotolerant, are able to control the pathogenic effects of trypanosomosis. Up to now, only one AFT breed, the longhorn N’Dama (NDA), has been largely studied and is considered as the reference trypanotolerant breed. Shorthorn taurine trypanotolerance has never been properly assessed and compared to NDA and AFZ breeds. Methodology/Principal Findings This study compared the trypanotolerant/susceptible phenotype of five West African local breeds that differ in their demographic history. Thirty-six individuals belonging to the longhorn taurine NDA breed, two shorthorn taurine Lagune (LAG) and Baoulé (BAO) breeds, the Zebu Fulani (ZFU) and the Borgou (BOR), an admixed breed between AFT and AFZ, were infected by Trypanosoma congolense IL1180. All the cattle were genetically characterized using dense SNP markers, and parameters linked to parasitaemia, anaemia and leukocytes were analysed using synthetic variables and mixed models. We showed that LAG, followed by NDA and BAO, displayed the best control of anaemia. ZFU showed the greatest anaemia and the BOR breed had an intermediate value, as expected from its admixed origin. Large differences in leukocyte counts were also observed, with higher leukocytosis for AFT. Nevertheless, no differences in parasitaemia were found, except a tendency to take longer to display detectable parasites in ZFU. Conclusions We demonstrated that LAG and BAO are as trypanotolerant as NDA. This study highlights the value of shorthorn taurine breeds, which display strong local adaptation to trypanosomosis. Thanks to further analyses based on comparisons of the genome or transcriptome of the breeds, these results open up the way for better knowledge

  11. Hypotaurine, N-methyltaurine, taurine, and glycine betaine as dominant osmolytes of vestimentiferan tubeworms from hydrothermal vents and cold seeps.

    PubMed

    Yin, M; Palmer, H R; Fyfe-Johnson, A L; Bedford, J J; Smith, R A; Yancey, P H

    2000-01-01

    Organic osmolytes, solutes that regulate cell volume, occur at high levels in marine invertebrates. These are mostly free amino acids such as taurine, which are "compatible" with cell macromolecules, and methylamines such as trimethylamine oxide, which may have a nonosmotic role as a protein stabilizer, and which is higher in many deep-sea animals. To better understand nonosmotic roles of osmolytes, we used high-performance liquid chromatography and (1)H-nuclear magnetic resonance (NMR) to analyze vestimentiferans (vestimentum tissue) from unusual marine habitats. Species from deep hydrothermal vents were Riftia pachyptila of the East Pacific Rise (2,636 m) and Ridgeia piscesae of the Juan de Fuca Ridge (2,200 m). Species from cold hydrocarbon seeps were Lamellibrachia sp. and an unnamed escarpid species from subtidal sediment seeps (540 m) off Louisiana and Lamellibrachia barhami from bathyal tectonic seeps (1,800-2,000 m) off Oregon. Riftia were dominated by hypotaurine (152 mmol/kg wet wt), an antioxidant, and an unidentified solute with an NMR spectrum consistent with a methylamine. Ridgeia were dominated by betaine (N-trimethylglycine; 109 mmol/kg), hypotaurine (64 mmol/kg), and taurine (61 mmol/kg). The escarpids were dominated by taurine (138 mmol/kg) and hypotaurine (69 mmol/kg). Both Lamellibrachia populations were dominated by N-methyltaurine (209-252 mmol/kg), not previously reported as a major osmolyte, which may be involved in methane and sulfate metabolism. Trunk and plume tissue of the Oregon Lamellibrachia were nearly identical to vestimentum in osmolyte composition. The methylamines may also stabilize proteins against pressure; they were significantly higher in the three deeper-dwelling groups. PMID:11073799

  12. Feature Hepatitis: The Dangers of Hepatitis: What you should know from A to E

    MedlinePlus

    ... Hepatitis: What you should know from A to E Past Issues / Spring 2009 Table of Contents For ... condition is called chronic hepatitis. Hepatitis A and E do not cause chronic hepatitis. Hepatitis viruses B, ...

  13. Viral hepatitis and hepatitis B antigen: recent advances

    PubMed Central

    Krugman, Saul

    1974-01-01

    Recent advances in hepatitis research have shed new light on the etiology, pathogenesis, epidemiology and prevention of type B hepatitis infection. The so-called ‘Dane’ particle is probably the complete hepatitis B virion; its outer coat is the hepatitis B (Australia) antigen (HB Ag) and its inner core is an immunologically distinct particle. Subtypes of HB Ag (a, d, y, w and r) are useful indices for epidemiological surveys. Concepts of epidemiology have changed: type B hepatitis is transmissible by contact as well as by inoculation. The presence of HB Ag in blood is indicative of the presence of hepatitis B virus. Tests to detect antigen and use of voluntary blood donors have played a major role in the decreased incidence of post transfusion hepatitis. A special hepatitis B gammaglobulin preparation and a heat-inactivated hepatitis B vaccine have proved to be effective in preliminary studies. PMID:4219230

  14. Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure

    PubMed Central

    Christophersen, Olav Albert

    2012-01-01

    There are several animal experiments showing that high doses of ionizing radiation lead to strongly enhanced leakage of taurine from damaged cells into the extracellular fluid, followed by enhanced urinary excretion. This radiation-induced taurine depletion can itself have various harmful effects (as will also be the case when taurine depletion is due to other causes, such as alcohol abuse or cancer therapy with cytotoxic drugs), but taurine supplementation has been shown to have radioprotective effects apparently going beyond what might be expected just as a consequence of correcting the harmful consequences of taurine deficiency per se. The mechanisms accounting for the radioprotective effects of taurine are, however, very incompletely understood. In this article an attempt is made to survey various mechanisms that potentially might be involved as parts of the explanation for the overall beneficial effect of high levels of taurine that has been found in experiments with animals or isolated cells exposed to high doses of ionizing radiation. It is proposed that taurine may have radioprotective effects by a combination of several mechanisms: (1) during the exposure to ionizing radiation by functioning as an antioxidant, but perhaps more because it counteracts the prooxidant catalytic effect of iron rather than functioning as an important scavenger of harmful molecules itself, (2) after the ionizing radiation exposure by helping to reduce the intensity of the post-traumatic inflammatory response, and thus reducing the extent of tissue damage that develops because of severe inflammation rather than as a direct effect of the ionizing radiation per se, (3) by functioning as a growth factor helping to enhance the growth rate of leukocytes and leukocyte progenitor cells and perhaps also of other rapidly proliferating cell types, such as enterocyte progenitor cells, which may be important for immunological recovery and perhaps also for rapid repair of various damaged

  15. Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure.

    PubMed

    Christophersen, Olav Albert

    2012-01-01

    There are several animal experiments showing that high doses of ionizing radiation lead to strongly enhanced leakage of taurine from damaged cells into the extracellular fluid, followed by enhanced urinary excretion. This radiation-induced taurine depletion can itself have various harmful effects (as will also be the case when taurine depletion is due to other causes, such as alcohol abuse or cancer therapy with cytotoxic drugs), but taurine supplementation has been shown to have radioprotective effects apparently going beyond what might be expected just as a consequence of correcting the harmful consequences of taurine deficiency per se. The mechanisms accounting for the radioprotective effects of taurine are, however, very incompletely understood. In this article an attempt is made to survey various mechanisms that potentially might be involved as parts of the explanation for the overall beneficial effect of high levels of taurine that has been found in experiments with animals or isolated cells exposed to high doses of ionizing radiation. It is proposed that taurine may have radioprotective effects by a combination of several mechanisms: (1) during the exposure to ionizing radiation by functioning as an antioxidant, but perhaps more because it counteracts the prooxidant catalytic effect of iron rather than functioning as an important scavenger of harmful molecules itself, (2) after the ionizing radiation exposure by helping to reduce the intensity of the post-traumatic inflammatory response, and thus reducing the extent of tissue damage that develops because of severe inflammation rather than as a direct effect of the ionizing radiation per se, (3) by functioning as a growth factor helping to enhance the growth rate of leukocytes and leukocyte progenitor cells and perhaps also of other rapidly proliferating cell types, such as enterocyte progenitor cells, which may be important for immunological recovery and perhaps also for rapid repair of various damaged

  16. Drug-induced hepatitis

    MedlinePlus

    ... induced hepatitis. Painkillers and fever reducers that contain acetaminophen are a common cause of liver inflammation. These ... problem. However, if you took high doses of acetaminophen , treatment should be started as soon as possible ...

  17. Hepatitis C and sex.

    PubMed

    Page, Emma E; Nelson, Mark

    2016-04-01

    An outbreak of acute hepatitis C among HIV-positive men who have sex with men (MSM) in the last decade has been shown to be sexually transmitted. Initially recreational drug use, in particular drug injection, was not prevalent among those becoming infected with hepatitis C. However more recently chemsex (the use of drugs to enhance sexual experience) and its associated drugs, which are not uncommonly injected, have become more frequently reported among those diagnosed with hepatitis C. It is hoped that the widespread -introduction of direct-acting antivirals and upscaling of numbers treated may have a positive impact on this epidemic. However their introduction may negatively impact on the perceived risk of acquiring hepatitis C and in conjunction with the introduction of HIV transmission prevention strategies may result in increased transmissions and spread to the HIV-negative MSM population. PMID:27037392

  18. Hepatitis C - children

    MedlinePlus

    ... chap 358. Jhaveri R. Hepatitis C virus. In: Cherry JD, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ, eds. Feigin and Cherry's Textbook of Pediatric Infectious Diseases. 7th ed. Philadelphia, ...

  19. Hepatitis Risk Assessment

    MedlinePlus

    ... About the Division of Viral Hepatitis Contact Us File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  20. [Patient education of hepatitis].

    PubMed

    Boyer, Dominique; Faillebin, Françoise; de la Brière, Aice

    2013-11-01

    The therapeutic education of patients with hepatitis C helps to improve their health and quality of life. The aim is to encourage compliance with the treatment and the fight against side effects, through to the patient's recovery. PMID:24409616

  1. Hepatitis B - children

    MedlinePlus

    ... kissing, coughing, or sneezing. Breast-feeding by a mother with hepatitis B is safe if the child is treated properly at the time of birth. Teenagers who are not vaccinated can get HBV during unprotected sex or drug use.

  2. Hepatitis B - children

    MedlinePlus

    ... tests detect liver damage and the risk for liver cancer from chronic hepatitis B: Albumin level Liver function tests Prothrombin time Liver biopsy Abdominal ultrasound Liver cancer tumor markers such as alpha fetoprotein The provider ...

  3. HIV and Viral Hepatitis

    MedlinePlus

    ... prevalent among blacks as among whites. Viral Hepatitis Transmission People can be infected with the three most ... risk for HAV. • • New data suggest that sexual transmission of HCV among MSM with HIV occurs more ...

  4. Hepatitis A FAQs

    MedlinePlus

    ... 185°F (85°C), kill the virus, although freezing temperatures do not. Symptoms Does Hepatitis A cause ... food, such as drinking beverages (with or without ice) of unknown purity, eating uncooked shellfish, and eating ...

  5. Chemoembolization of hepatic malignancy.

    PubMed

    Gonsalves, Carin F; Brown, Daniel B

    2009-01-01

    Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization represents an essential component of interventional oncology. This article discusses patient selection, procedure technique, results, and complications associated with transarterial chemoembolization. PMID:18668189

  6. Imaging of hepatic infections.

    PubMed

    Doyle, D J; Hanbidge, A E; O'Malley, M E

    2006-09-01

    Imaging plays a significant role in the detection, characterization and treatment of hepatic infections. Infectious diseases of the liver include pyogenic and amoebic abscesses and parasitic, fungal, viral and granulomatous infections. With increases in worldwide travel, immunosuppression and changing population demographics, identification of cases of hepatic infection is becoming more common in daily practice. Knowledge of the imaging features seen with hepatic infections can assist in early diagnosis and timely initiation of appropriate therapy. This review presents the imaging appearances of hepatic infections, emphasizing specific features that may contribute to the diagnosis. Examples of the imaging findings seen with pyogenic and amoebic abscesses, infection with Echinococcus granulosus (Hydatid), schistosomiasis, candidiasis and tuberculosis (TB) are presented. PMID:16905380

  7. Human hereditary hepatic porphyrias.

    PubMed

    Nordmann, Yves; Puy, Hervé

    2002-11-01

    The human hereditary hepatic porphyrias are diseases due to marked deficiencies of enzymes in the heme biosynthetic pathway. Porphyrias can be classified as either hepatic or erythroid, depending on the major production site of porphyrins or their precursors. The pathogenesis of inherited hepatic porphyrias has now been defined at the molecular level. Some gene carriers are vulnerable to a range of exogenous and endogenous factors, which may trigger neuropsychiatric and/or cutaneous symptoms. Early diagnosis is of prime importance since it makes way for counselling. In this article we present an overview of recent advances on hepatic porphyrias: 5-aminolevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria (AIP), porphyria cutanea tarda (PCT), hereditary coproporphyria (HC), and variegate porphyria (VP). PMID:12367763

  8. Hepatitis D Virus Replication.

    PubMed

    Taylor, John M

    2015-11-01

    This work reviews specific related aspects of hepatitis delta virus (HDV) reproduction, including virion structure, the RNA genome, the mode of genome replication, the delta antigens, and the assembly of HDV using the envelope proteins of its helper virus, hepatitis B virus (HBV). These topics are considered with perspectives ranging from a history of discovery through to still-unsolved problems. HDV evolution, virus entry, and associated pathogenic potential and treatment of infections are considered in other articles in this collection. PMID:26525452

  9. Co-treatment of chlorpyrifos and lead induce serum lipid disorders in rats: Alleviation by taurine.

    PubMed

    Akande, Motunrayo G; Aliu, Yusuf O; Ambali, Suleiman F; Ayo, Joseph O

    2016-07-01

    The aim of this study was to investigate the effects of taurine (TA) on serum lipid profiles following chronic coadministration of chlorpyrifos (CP) and lead acetate (Pb) in male Wistar rats. Fifty rats randomly distributed into five groups served as subjects. Distilled water (DW) was given to DW group, while soya oil (SO; 1 mL kg(-1)) was given to SO group. The TA group was treated with TA (50 mg kg(-1)). The CP + Pb group was administered sequentially with CP (4.25 mg kg(-1); 1/20th median lethal dose (LD50)) and Pb at 233.25 mg kg(-1) (1/20th LD50), while the TA + CP + Pb group received TA (50 mg kg(-1)), CP (4.25 mg kg(-1)), and Pb (233.25 mg kg(-1)) sequentially. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanised, and the blood samples were collected at the termination of the study. Sera obtained from the blood samples were analyzed for total cholesterol, high-density lipoprotein cholesterol, triglycerides, and malondialdehyde, and also the activities of serum antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase were analyzed. The low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and atherogenic index were calculated. The results showed that CP and Pb induced alterations in the serum lipid profiles and evoked oxidative stress. TA alleviated the disruptions in the serum lipid profiles of the rats partially by mitigating oxidative stress. It was concluded that TA may be used for prophylaxis against serum lipid disorders in animals that were constantly co-exposed to CP and Pb in the environment. PMID:25537622

  10. Modulatory action of taurine on ethanol-induced aggressive behavior in zebrafish.

    PubMed

    Fontana, Barbara D; Meinerz, Daniele L; Rosa, Luiz Vinícius C; Mezzomo, Nathana J; Silveira, Ariane; Giuliani, Giulie S; Quadros, Vanessa A; Filho, Gilvan L B; Blaser, Rachel E; Rosemberg, Denis B

    2016-02-01

    Alcohol is a potent agent for eliciting aggression in vertebrates. Taurine (TAU) is an amino sulfonic acid with pleiotropic actions on brain function. It is one of the most abundant molecules present in energy drinks frequently used as mixers for alcoholic beverages. However, the combined effects of TAU and ethanol (EtOH) on behavioral parameters such as aggression are poorly understood. Considering that zebrafish is a suitable vertebrate to assess agonistic behaviors using noninvasive protocols, we investigate whether TAU modulates EtOH-induced aggression in zebrafish using the mirror-induced aggression (MIA) test. Since body color can be altered by pharmacological agents and may be indicative of emotional state, we also evaluated the actions of EtOH and TAU on pigment response. Fish were acutely exposed to TAU (42, 150, and 400mg/L), EtOH (0.25%), or cotreated with both molecules for 1h and then placed in the test apparatus for 6min. EtOH, TAU 42, TAU 400, TAU 42/EtOH and TAU 400/EtOH showed increased aggression, while 150mg/L TAU only increased the latency to attack the mirror. This same concentration also prevented EtOH-induced aggression, suggesting that it antagonizes the effects of acute alcohol exposure. Representative ethograms revealed the existence of different aggressive patterns and our results were confirmed by an index used to estimate aggression in the MIA test. TAU did not alter pigment intensity, while EtOH and all cotreated groups presented a substantial increase in body color. Overall, these data show a biphasic effect of TAU on EtOH-induced aggression of zebrafish, which is not necessarily associated with changes in body color. PMID:26631619

  11. Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria.

    PubMed

    Zhang, Xiali; Lu, Hongfei; Wang, Yibing; Liu, Chunju; Zhu, Weifeng; Zheng, Shuangyan; Wan, Fusheng

    2015-01-01

    Taurine (Tau), the most abundant free amino acid in humans has numerous potential health benefits through its antioxidant and anti-inflammatory properties. However, limited studies have assessed its effect on tumors and the antitumor mechanism remains unknown. The present study investigated the cellular and molecular changes induced by Tau, leading to the induction of apoptosis in human breast cancer cell lines MCF-7 and MDA-MB-231. MCF-7 is p53 proficient (p53+/+) and MDA-MB-231 is a p53 null mutant (p53-/-). Cell proliferation and viability were assessed by MTT. Flow cytometry and hoechst33342 fluorescent staining were employed to detect apoptosis. Spectrophotometry was used to detect caspase-3 activity. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect the levels of mRNA and proteins of p53-upregulated modulator of apoptosis (PUMA), Bax and Bcl-2. Finally, the affect of Tau on the growth of MDA-MB-231-cell-nude mice xenografts was examined. In the study, Tau inhibited growth and induced apoptosis of the two cell lines in a concentration- and time-dependent manner. Notably, the inhibitory effect of Tau on p53-/- cancer cells was clearly significant compared to the p53+/+ cancer cells. Further studies showed that Tau promoted apoptosis in human breast cancer cells and inhibited the growth of tumor in nude mice by inducing the expression of PUMA, which further up- and downregulated the expression of Bax and Bcl-2 protein, giving rise to increased activation of caspase-3. Collectively, these results indicate that Tau is a potent candidate for the chemotherapy of breast cancer through increasing the PUMA expression independent of p53 status. PMID:25395275

  12. Taurine improves the wound healing process in cutaneous leishmaniasis in mice model, based on stereological parameters

    PubMed Central

    Ashkani-Esfahani, Soheil; Zarifi, Fariba; Asgari, Qasem; Samadnejad, Asal Zargari; Rafiee, Shima; Noorafshan, Ali

    2014-01-01

    Background: Cutaneous Leishmaniasis is a self-limiting disease caused by protozoan parasites of the genus Leishmania, which affects the skin with full-thickness wounds, which are prone to scar formation even after treatment. Taurine (Tu) is one of the most abundant amino acids that has antioxidant and anti-inflammatory effects, which play an important role in the process of wound healing. Herein, we have investigated the effects of Tu on cutaneous Leishmaniasis wounds and L. major promastigotes. Materials and Methods: Eighteen mice were induced with Leishmaniasis wounds (with L. Major) on the base of their tails and divided into three groups, T1: Treated with Tu injection, T2: Treated with Tu gel, and C: No treatment. Treatments were carried out every 24 hours for 21 days. The volume densities of the collagen bundles and vessels, vessel's length density and diameter, and fibroblast populations were estimated by stereological methods. Flow cytometry was used in order to investigate the direct Tu effect on parasites. The Mann-Whitney U test was used and P ≤ 0.05 was considered to be statistically significant. Results: The numerical density of the fibroblasts, volume density of the collagen bundles, and length densities of the vessels in groups T1 and T2 were significantly higher than in group C (P < 0.05). The fibroblast numerical density of group T1 was higher than that of group T2 (P = 0.02). Incidentally, Tu had no direct effect on L. major parasites according to the flow cytometry analysis. Conclusion: Tu showed the ability to improve the wound healing process and tissue regeneration although it had no direct anti-leishmaniasis effect. PMID:25337534

  13. Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model.

    PubMed

    Aydın, A Fatih; Çoban, Jale; Doğan-Ekici, Işın; Betül-Kalaz, Esra; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-04-01

    D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; β-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats. PMID:26518192

  14. Immigration and viral hepatitis.

    PubMed

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants. PMID:25962882

  15. Delta hepatitis in Malaysia.

    PubMed

    Sinniah, M; Dimitrakakis, M; Tan, D S

    1986-06-01

    Sera from one hundred and fifty nine Malaysian individuals were screened for the prevalence of delta markers. These included 15 HBsAg positive homosexuals, 16 acute hepatitis B cases, 9 chronic hepatitis B patients, 13 healthy HBsAg carriers and 106 intravenous (i.v.) drug abusers, of whom 27 were positive for HBsAg only and the rest were anti-HBc IgG positive but HBsAg negative. The prevalence of delta markers in the homosexuals was found to be 6.7%, in the HBsAg positive drug abusers 17.8%, in acute hepatitis B cases 12.5%. No evidence of delta infection was detected in healthy HBsAg carriers, chronic hepatitis B cases and HBsAg negative i.v. drug abusers. With reference to i.v. drug abusers, the prevalence of delta markers was higher in Malays (23%) than in Chinese (7%) although the latter had a higher HBsAg carrier rate. Although the HBsAg carrier rate in the homosexuals was high, their delta prevalence rate was low as compared to drug abusers. In Malaysia, as in other non-endemic regions, hepatitis delta virus transmission appeared to occur mainly via the parenteral and sexual routes. This is the first time in Malaysia that a reservoir of delta infection has been demonstrated in certain groups of the population at high risk for hepatitis B. PMID:3787309

  16. Methionine excess in diet induces acute lethal hepatitis in mice lacking cystathionine γ-lyase, an animal model of cystathioninuria.

    PubMed

    Yamada, Hidenori; Akahoshi, Noriyuki; Kamata, Shotaro; Hagiya, Yoshifumi; Hishiki, Takako; Nagahata, Yoshiko; Matsuura, Tomomi; Takano, Naoharu; Mori, Masatomo; Ishizaki, Yasuki; Izumi, Takashi; Kumagai, Yoshito; Kasahara, Tadashi; Suematsu, Makoto; Ishii, Isao

    2012-05-01

    Physiological roles of the transsulfuration pathway have been recognized by its contribution to the synthesis of cytoprotective cysteine metabolites, such as glutathione, taurine/hypotaurine, and hydrogen sulfide (H(2)S), whereas its roles in protecting against methionine toxicity remained to be clarified. This study aimed at revealing these roles by analyzing high-methionine diet-fed transsulfuration-defective cystathionine γ-lyase-deficient (Cth(-/-)) mice. Wild-type and Cth(-/-) mice were fed a standard diet (1 × Met: 0.44%) or a high-methionine diet (3 × Met or 6 × Met), and hepatic conditions were monitored by serum biochemistry and histology. Metabolome analysis was performed for methionine derivatives using capillary electrophoresis- or liquid chromatography-mass spectrometry and sulfur-detecting gas chromatography. The 6 × Met-fed Cth(-/-) (not 1 × Met-fed Cth(-/-) or 6 × Met-fed wild type) mice displayed acute hepatitis, which was characterized by markedly elevated levels of serum alanine/aspartate aminotransferases and serum/hepatic lipid peroxidation, inflammatory cell infiltration, and hepatocyte ballooning; thereafter, they died of gastrointestinal bleeding due to coagulation factor deficiency. After 1 week on 6 × Met, blood levels of ammonia/homocysteine and hepatic levels of methanethiol/3-methylthiopropionate (a methionine transamination product/methanethiol precursor) became significantly higher in Cth(-/-) mice than in wild-type mice. Although hepatic levels of methionine sulfoxide became higher in 6 × Met-fed wild-type mice and Cth(-/-) mice, those of glutathione, taurine/hypotaurine, and H(2)S became lower and serum levels of homocysteine became much higher in 6 × Met-fed Cth(-/-) mice than in wild-type mice. Thus, transsulfuration plays a critical role in the detoxification of excessive methionine by circumventing aberrant accumulation of its toxic transamination metabolites, including ammonia, methanethiol, and 3-methylthiopropionate

  17. Sensory profile of a model energy drink with varying levels of functional ingredients-caffeine, ginseng, and taurine.

    PubMed

    Tamamoto, Lauren C; Schmidt, Shelly J; Lee, Soo-Yeun

    2010-08-01

    Energy drinks have increased in popularity in recent years due to the claimed energy boost provided by functional ingredients. A multitude of functional ingredients have been utilized; however, there is limited research on their sensory effects in energy drink formulations. A 13-member descriptive analysis panel was conducted to investigate the effects on the sensory and rheological properties of 3 common functional ingredients-caffeine, ginseng, and taurine-in a noncarbonated model energy drink solution. Combinations of these functional ingredients at 3 levels (low, medium, high) were added to create a total of 27 different solutions (3 x 3 x 3 factorial design). Analysis of variance was performed to evaluate the sensory effects of the varying concentrations of functional ingredients in solution. Principal component analysis (PCA) was performed to summarize the relationship among the attributes and solutions. In general, high levels of caffeine in solution resulted in low ratings of fruity attributes and high ratings of bitter tea and fruit bitter attributes. The high level of ginseng in solution was characterized by high ratings of bitter attributes. A horns effect was observed as the sweet, artificial lemon-lime, pear, mango, and pineapple attributes were rated lower in intensity with increased ginseng levels. Taurine levels of up to 416 mg/100 mL had no significant effect on the sensory attribute ratings of the model energy drink solutions. These findings can be utilized to predict the changes in sensory characteristics when formulating energy drinks containing these popular functional ingredients. PMID:20722948

  18. Topical taurine bromamine, a new candidate in the treatment of moderate inflammatory acne vulgaris: a pilot study.

    PubMed

    Marcinkiewicz, Janusz; Wojas-Pelc, Anna; Walczewska, Maria; Lipko-Godlewska, Sylwia; Jachowicz, Renata; Maciejewska, Aldona; Białecka, Anna; Kasprowicz, Andrzej

    2008-01-01

    Taurine bromamine (TauBr), the product of taurine and hypobromous acid (HOBr), exerts anti-inflammatory and antibacterial properties. Recently we have shown that Propionibacterium acnes, a potential pathogenic agent of acne, is extremely sensitive to TauBr. As topical antibiotics are associated with the emergence of resistant bacteria, TauBr seems to be a good candidate for topical therapy for acne vulgaris. In our double blind investigation, the efficacy and safety of 3.5 mM TauBr cream was evaluated. 1% Clindamycin gel (Clindacin T), one of the most common topical agents in the treatment of acne vulgaris, was used as a control. Forty patients with mild to moderate inflammatory facial acne vulgaris were randomly treated with either TauBr or clindamycin for 6 weeks, twice-a-day. More than 80% of the patients markedly improved with both treatments, without any adverse effects observed. Both TauBr and clindamycin produced a significant reduction in inflammatory skin lesion counts (papules/ pustules). After 6 weeks, comparable reductions of acne lesions, 65% and 68%, were observed in the TauBr and clindamycin groups, respectively. In conclusion, these data support our concept that TauBr can be used as a topical agent in the treatment of acne vulgaris, especially in patients who have already developed antibiotic resistance. PMID:18573718

  19. Taurine supplementation of plant derived protein 1 and n-3 fatty acids are critical for optimal growth and development of cobia, rachycentron canadum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined growth performance and lipid content in juvenile cobia, Rachycentron canadum, fed a taurine supplemented (1.5%), plant protein based diet with two fish oil replacements. The first fish oil replacement was a thraustochytrid meal (TM+SOY) plus soybean oil (~9% CL) and the second was a cano...

  20. Protection by taurine against INOS-dependent DNA damage in heavily exercised skeletal muscle by inhibition of the NF-κB signaling pathway.

    PubMed

    Sugiura, Hiromichi; Okita, Shinya; Kato, Toshihiro; Naka, Toru; Kawanishi, Shosuke; Ohnishi, Shiho; Oshida, Yoshiharu; Ma, Ning

    2013-01-01

    Taurine protects against tissue damage in a variety of models involving inflammation, especially the muscle. We set up a heavy exercise bout protocol for rats consisting of climbing ran on a treadmill to examine the effect of an intraabdominal dose of taurine (300 mg/kg/day) administered 1 h before heavy exercise for ten consecutive days. Each group ran on the treadmill at 20 m/min, 25% grade, for 20 min or until exhaustion within 20 min once each 10 days. Exhaustion was the point when an animal was unable to right itself when placed on its side. The muscle damage was associated with an increased accumulation of 8-nitroguanine and 8-OHdG in the nuclei of skeletal muscle cells. The immunoreactivities for NF-κB and iNOS were also increased in the exercise group. Taurine ameliorated heavy exercise-induced muscle DNA damage to a significant extent since it reduced the accumulation of 8-nitroguanine and 8-OHdG, possibly by down-regulating the expression of iNOS through a modulatory action on NF-κB signaling pathway. This study demonstrates for the first time that taurine can protect against intense exercise-induced nitrosative inflammation and ensuing DNA damage in the skeletal muscle of rats by preven