Taurine Exposure Research Articles

Feasibility exploration of GSH in the treatment of acute hepatic encephalopathy from the aspects of pharmacokinetics, pharmacodynamics, and mechanism.

Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.

Taurine rescues pancreatic β-cell stress by stimulating α-cell transdifferentiation.

The semi-essential ubiquitous amino acid taurine has been shown to alleviate obesity and hyperglycemia in humans; however, the pathways underlying the antidiabetic actions have not been characterized. We explored the effect of chronic taurine exposure on cell biology of pancreatic islets, in degenerative type 1-like diabetes. The latter was modeled by small dose of streptozotocin (STZ) injection for 5 days in mice, followed by a 10-day administration of taurine (2% w/v, orally) in the drinking water. Taurine treatment opposed the detrimental changes in islet morphology and β-/α-cell ratio, induced by STZ diabetes, coincidentally with a significant 3.9 ± 0.7-fold enhancement of proliferation and 40 ± 5% reduction of apoptosis in β-cells. In line with these findings, the treatment counteracted an upregulation of antioxidant (Sod1, Sod2, Cat, Gpx1) and downregulation of islet expansion (Ngn3, Itgb1) genes induced by STZ, in a pancreatic β-cell line. At the same time, taurine enhanced the transdifferentiation of α-cells into β-cells by 2.3 ± 0.8-fold, echoed in strong non-metabolic elevation of cytosolic Ca2+ levels in pancreatic α-cells. Our data suggest a bimodal effect of dietary taurine on islet β-cell biology, which combines the augmentation of α-/β-cell transdifferentiation with downregulation of apoptosis. The dualism of action, stemming presumably from the intra- and extracellular modality of the signal, is likely to explain the antidiabetic potential of taurine supplementation.

Caffeine, D-glucuronolactone and Taurine Content in Energy Drinks: Exposure and Risk Assessment

The consumption of energy drinks (EDs) is increasing globally while the evidence and concern about the potential health risks are also growing. Caffeine (generally 32 mg/100 mL) together with a wide variety of other active components such as taurine (usually 4000 mg/L) and D-glucuronolactone (generally 2400 mg/L) are the main ingredients of EDs. This study aims to assess the exposures to caffeine, taurine and D-glucuronolactone from EDs in various consumption scenarios and consumer profiles and to characterize the risks by evaluating caffeine and taurine intakes with their reference values and by calculating the margin of safety (MOS) for D-glucuronolactone. While the exposure assessment results showed that caffeine intakes from EDs ranged from 80 to 160 mg (1.14-4 mg/kg b.w.) for the considered scenarios, the risk characterization estimated some risks that could be managed with consumption recommendations such as limiting EDs in 40, 60 and 80 kg b.w. consumers to 175, 262.5 and 350 mL, respectively, to prevent sleep disturbances and to 375, 562.5 and 750 mL to prevent general caffeine adverse health risks, respectively. Dietary exposure to D-glucuronolactone from EDs ranged from 600 to 1200 mg (7.5-30 mg/kg b.w.). As D-glucuronolactone MOS ≥ 100 is only observed when EDs consumption is limited to 250 mL, for individuals weighing above 60 kg, some risks were observed in some of the studied scenarios. A taurine exposure from EDs varied from 1000 to 2000 mg (12.5-50 mg/kg b.w.) and consumptions over 500 mL were estimated to generate intakes above the reference value. In conclusion, the management of these risks requires a European legal framework for EDs with maximum limits for the active components, volume size limitations and labeling improvements along with the development of education and awareness programs and risk communication actions in collaboration with the industry and society.

Concomitant taurine exposure counteracts ethanol-induced changes in locomotor and anxiety-like responses in zebrafish

Taurine (TAU) is a β-amino sulfonic acid with pleiotropic roles in the brain, including the neuromodulatory activity via GABAergic and glycinergic agonism. This molecule is found at high concentrations in energy drinks and is often mixed with alcohol in beverages. Although TAU has a neuroprotective role in the brain, the putative risks of mixing TAU and EtOH are not fully understood. Here, we investigated whether TAU modulates locomotor and anxiety-like behavior in adult zebrafish by using the novel tank and light-dark tests following acute EtOH exposure at anxiogenic and anxiolytic concentrations. Zebrafish were individually exposed to water (control), TAU (42, 150, and 400 mg/L), and EtOH (0.25% (v/v) and 1% (v/v)) both independently and cotreated for 1 h. EtOH 0.25% and TAU produced U-shape anxiolytic-like behavior in the light-dark test, TAU 42 and 400 positively modulated EtOH effects, and TAU 150 exerted a protective effect. All TAU concentrations counteracted EtOH 1%-induced locomotion impairment, as well as the anxiogenic-like behavior. Finally, all TAU concentrations when given independently or cotreated with EtOH 0.25% and 1% decreased the risk assessment of the lit compartment. Principal component analyses revealed that exploration and anxiety-like responses were the main behaviors that contribute to the effects of TAU and EtOH. Overall, we demonstrate that TAU differently modulates EtOH-induced anxiolytic- and anxiogenic-like behaviors depending on the concentration, suggesting a complex mechanism underlying TAU and EtOH interactions.

Bone microstructure of mice after prolonged taurine treatment.

Taurine, a sulphur - containing amino acid, has been termed a functional nutrient. Its synthetic form is a common ingredient in supplements and energy drinks. There is no information concerning taurine impact on bone microstructure after prolonged supplemental use. Also, differences in bone parameters of mice following taurine exposure are unknown. In this study, a detailed microstructure of compact and trabecular bone tissues of mice subchronically exposed to taurine was determined. Animals (n=12) were segregated into three groups: E1 group - mice received 20 mg/kg b.w. of taurine per day during 8 weeks; E2 group - mice were fed by taurine at a dose of 40 mg/kg b.w. for 8 weeks and a control (C) group. Decreased density of secondary osteons, increased sizes of primary osteon's vascular canals (P<0.05) were observed in taurine - treated animals. Cortical bone thickness, trabecular thickness were decreased (P<0.05) in E1 group, and relative volume of trabecular bone was lower (P<0.05) in E2 group as compared to C group. According to our results, prolonged taurine exposure at the doses used in this study can negatively affect both compact and trabecular bone tissues microstructure.

Taurine: A Rescuer of Neurodegenerative Dysfunction?

Alzheimer's disease (AD), is characterized by an accumulation of amyloid plaques that contribute to neurodegeneration. Taurine is a very essential amino acid in the nervous system, but is one of a few not used to synthesize proteins. It is found in fish, eggs, and organ meat; however, taurine is better known as a supplement in energy drinks with the purpose of depressing nervous system function. Taurine has been shown in previous studies to increase memory retention in mice. Our project aims to determine the impact of taurine on a mutant strain of C. elegans, ynIs‐79, which overexpresses the APL‐1 protein in the nervous system. We expect that supplementing the mutant nematodes' diet with taurine will positively influence the nervous system by rescuing the observed dysfunction. We tested anterior and posterior habituation following taurine exposure by tapping the worms with a sterilized eyelash until they recognized that the taps were a non‐threatening stimulus. Our hypothesis is that feeding nematodes taurine will result in a decrease in the number of taps required for the mutant nematodes to determine that it is not a harmful stimulus, suggesting an improvement in neurodegenerative dysfunction. Current results show a significant decrease in the number taps required for habituation in the ynIs‐79 strain when compared to controls.Support or Funding InformationGail Dillard Faculty Development FundingThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Chondroprotective effects of taurine in primary cultures of human articular chondrocytes.

Articular cartilage is characterized by the lack of blood vessels and has a poor self-healing potential. Limited cell numbers and dedifferentiation of chondrocytes when expanded in vitro are the major obstacles of autologous chondrocyte implantation. Autologous chondrocyte implantation is a cell-based treatment that can be used as a second-line measure to regenerate chondral or osteochondral defects in younger, active patients. There is an urgent need to find an effective chondrogenic protection agent alleviating or inhibiting chondrocyte dedifferentiation. In this study, we explored the effect of taurine (2-aminoethane sulfonic acid) on proliferation and phenotype maintenance of human articular chondrocytes by analyzing the cell proliferation, morphology, viability, and expression of cartilage specific mRNAs and proteins. Primary chondrocytes were isolated from human articular cartilage tissues. Results showed that taurine effectively promoted chondrocyte growth and enhanced accumulation of glycosaminoglycans and collagens in the conditioned media of chondrocytes. Moreover, taurine exposure caused significant increases in the relative expression levels of mRNAs for cartilage specific markers, including aggrecan, collagen type II and SOX9. Aggrecan is a cartilage-specific proteoglycan, and SOX9 is a chondrogenic transcription factor. In contrast, the mRNA expression of collagen type I, a marker for chondrocyte dedifferentiation, was significantly decreased in cells treated with taurine, indicating that taurine inhibits the chondrocyte dedifferentiation. This study reveals that taurine is effective in proliferation promotion and phenotype maintenance of chondrocytes. Thus, taurine may be a useful pro-chondrogenic agent for autologous chondrocyte implantation in the treatment of cartilage repair.

Perinatal taurine depletion increases oxidative stress in adult female rats

Our previous studies and those of others demonstrate that perinatal taurine exposure affects adult physiology and susceptibility to disease in several animal models of cardiovascular and renal disease. Perinatal taurine depletion typically produces adult disorders, but perinatal taurine supplementation minimally influences normal physiology in adults. This study tests the hypothesis that perinatal taurine depletion leads to increased oxidative stress in adult female rats. Female Sprague‐Dawley rats were fed normal rat chow with 3% β‐alanine (taurine deficient, TD), 3% taurine (taurine supplemented, TS) or water alone (C) from conception to weaning. Their female offspring were fed normal rat chow and water alone throughout the experiment. At 7–8 weeks of age, body, kidney and heart weights were not significantly different among groups (n = 10/group). Neither did their plasma sodium, plasma potassium, mean arterial pressure and heart rate. Compared to control, plasma malondialdehyde levels (a bio‐marker of oxidative stress from lipid peroxidation) were significantly higher in TD and the TS group was intermediate between the other two groups, i.e., not significantly different than either. These results suggest that perinatal taurine depletion increases oxidative stress in adult female rats and could play a role in the morbidity of these animals as they mature through adulthood.

Perinatal taurine exposure affects adult arterial pressure control

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.

The augmentative action of taurine on the differentiation of C2C12 cells to myotube

Background/AimIncomplete muscular development is induced by deficiency of taurine that is endogenously and abundantly supplied thought placenta and milk via a specific transporter (TAUT). This study investigated the influence of taurine on the differentiation of myoblast.MethodConfluent mice myoblast (C2C12) cell was exposed to up to 20mM taurine with a differentiation medium for up to a week. The differentiation markers were evaluated by RT‐qPCR, fluorescence immunohistochemical stain or Western blot. The influences of cellular taurine uptake inhibition on the myoblast differentiation were also examined.ResultThe fusion index and maximal diameter in the MHC‐positive myotubes were significantly increased, in particular 6‐fold in 20mM taurine, compared to those in 0mM taurine. The phosphorylations of Akt and p38MAPK were increased and decreased, respectively, by taurine. Furthermore, the expression of myostatin protein was suppressed by taurine exposure. The differentiations in exposing to 20mM taurine were significantly inhibited by taut siRNA or β‐alanine; a taurine transport competitor.ConclusionExogenous taurine might play a key role on the skeletal muscle differentiation during development period. The effects of taurine should contribute the recovery from muscle damages and differentiation of satellite cells.

Evidence that acute taurine treatment alters extracellular AMP hydrolysis and adenosine deaminase activity in zebrafish brain membranes

Taurine is one of the most abundant free amino acids in excitable tissues. In the brain, extracellular taurine may act as an inhibitory neurotransmitter, neuromodulator, and neuroprotector. Nucleotides are ubiquitous signaling molecules that play crucial roles for brain function. The inactivation of nucleotide-mediated signaling is controlled by ectonucleotidases, which include the nucleoside triphosphate diphosphohydrolase (NTPDase) family and ecto-5′-nucleotidase. These enzymes hydrolyze ATP/GTP to adenosine/guanosine, which exert a modulatory role controlling several neurotransmitter systems. The nucleoside adenosine can be inactivated in extracellular or intracellular milieu by adenosine deaminase (ADA). In this report, we tested whether acute taurine treatment at supra-physiological concentrations alters NTPDase, ecto-5′-nucleotidase, and ADA activities in zebrafish brain. Fish were treated with 42, 150, and 400 mg L −1 taurine for 1 h, the brains were dissected and the enzyme assays were performed. Although the NTPDase activities were not altered, 150 and 400 mg L −1 taurine increased AMP hydrolysis (128 and 153%, respectively) in zebrafish brain membranes and significantly decreased ecto-ADA activity (29 and 38%, respectively). In vitro assays demonstrated that taurine did not change AMP hydrolysis, whereas it promoted a significant decrease in ecto-ADA activity at 150 and 400 mg L −1 (24 and 26%, respectively). Altogether, our data provide the first evidence that taurine exposure modulates the ecto-enzymes responsible for controlling extracellular adenosine levels in zebrafish brain. These findings could be relevant to evaluate potential beneficial effects promoted by acute taurine treatment in the central nervous system (CNS) of this species.

High dietary sugar exacerbates cardiac reperfusion injury in perinatal taurine depleted adult rats

Reperfusion injury triggers acute and chronic damage to multiple organs. Taurine treatment appears to reduce these injuries. This study tests the hypothesis that perinatal taurine exposure reduces the severity of cardiac reperfusion injury in the adult male rats. Female Sprague‐Dawley rats were fed normal rat chow with 3% beta‐alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS) or water alone (control, C) from conception to weaning. Male offspring were fed normal rat chow and water containing 5% glucose (CG, TSG, TDG) or water alone (CW, TSW, TDW) throughout the experiment. At 7–8 weeks of age, all rats were anesthetized and their trachea clamped until cardiac arrest occurred and mean arterial pressure fell below 60 mm Hg. The clamp was immediately released and cardiopulmonary resuscitation was performed with cardiac function returning within 4 min. Circulating markers of cardiac injury were measured 2 days later. Plasma aspartate aminotransferase increased in all glucose treated and TDW rats, but the increase was nearly 3X greater in TDG vs. any other group. Creatine kinase‐MB increased in all treatment groups but was far greater in TD than other groups. Troponin‐I and brain natriuretic peptide were greatly increased in TDG compared to all other groups. These data indicate that high dietary sugar together with early life taurine depletion exacerbates cardiac reperfusion damage in adult rats.

Adult renal function is modified by perinatal taurine status in conscious male rats

Perinatal taurine exposure influences renal function in adult female offspring. This study tests the hypothesis that prenatal rather than postnatal taurine exposure alters renal function in adult conscious male rats. Female Sprague Dawley rats were fed normal rat chow and tap water alone (Control), tap water containing 3% β-alanine (taurine depletion, TD) or tap water containing 3% taurine (taurine supplementation, TS) either from conception until delivery (fetal period; TDF or TSF) or from delivery until weaning (lactation period; TDL or TSL). After weaning, male offspring were fed with the normal rat chow and tap water ad libitum. At 7-8 weeks of age, renal function was studied in conscious, restrained rats. Mean arterial pressures were slightly higher in rats receiving taurine supplementation during either the fetal or lactation periods (compared to Control and TD groups), but heart rates were not significantly different among groups. Effective renal blood flows were lower in TDF, TDL, and TSF rats (TDF 4.6±0.8 ml/min/g kidney weight (KW), TDL 3.0±0.9 ml/min/g KW, and TSF 2.8±0.7 ml/min/g KW) than in TSL (7.7±0.9 ml/min/g KW) or Control rats (7.3±1.6 ml/min/g KW). These differences were correlated with significant increases in renal vascular resistance in TDF, TDL, and TSF groups compared to TSL and Control rats. In contrast, glomerular filtration rates were not significantly different among groups. Although basal water and sodium excretion were slightly lower in TDL and TSF rats compared to other groups, their diuretic and natriuretic responses to an acute saline load were not different from Control. The present data indicate that in adult male rats, both perinatal supplementation and depletion of taurine can alter renal hemodynamics, and these effects are differentially time-dependent.

Perinatal taurine exposure alters renal potassium excretion mechanisms in adult conscious rats

Perinatal taurine exposure has long-term effects on the arterial pressure and renal function. This study tests its influence on renal potassium excretion in young adult, conscious rats. Female Sprague-Dawley rats were fed normal rat chow and given water alone (C), 3% beta-alanine in water (taurine depletion, TD) or 3% taurine in water (taurine supplementation, TS), either from conception until delivery (fetal period; TDF or TSF) or from delivery until weaning (lactation period; TDL or TSL). In Experiment 1, male offspring were fed normal rat chow and tap water, while in Experiment 2, beta-alanine and taurine were treated from conception until weaning and then female pups were fed normal rat chow and 5% glucose in drinking water (CG, TDG or TSG) or water alone (CW, TDW or TSW). At 7-8 weeks of age, renal potassium excretion was measured at rest and after an acute saline load (5% of body weight) in conscious, restrained rats. Although all male groups displayed similar renal potassium excretion, TSF rats slightly increased fractional potassium excretion at rest but not in response to saline load, whereas TDF did the opposite. Plasma potassium concentration was only slightly altered by the diet manipulations. In female offspring, none of the perinatal treatments significantly altered renal potassium excretion at rest or after saline load. High sugar intake slightly decreased potassium excretion at rest in TDG and TSG, but only the TDG group displayed a decreased response to saline load. The present data indicates that perinatal taurine exposure only mildly influences renal potassium excretion in adult male and female rats.

High sugar intake exacerbates cardiac reperfusion injury in perinatal taurine depleted adult rats

Perinatal taurine depletion and high sugar diets blunted baroreflex function and heightens sympathetic nerve activity in adult rats. Cardiac ischemia/reperfusion also produces these disorders and taurine treatment appears to improve these effects. This study tests the hypothesis that perinatal taurine exposure predisposes recovery from reperfusion injury in rats on either a basal or high sugar diet. Female Sprague-Dawley rats were fed normal rat chow with 3% beta-alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS) or water alone (control, C) from conception to weaning. Male offspring were fed normal rat chow and water containing 5% glucose (G) or water alone (W) throughout the experiment. At 7-8 weeks of age, all rats were anesthetized and their trachea clamped until cardiac arrest occurred and mean arterial pressure fell below 60 mm Hg. The clamp was immediately released and cardiopulmonary resuscitation was performed with cardiac function returning within 4 min. Twenty-four hours later, arterial pressure, heart rate, and baroreflex function were measured in conscious and one day later in anesthetized conditions. Basic blood chemistry and circulating markers of cardiac injury were also measured. Baroreflex sensitivity was depressed moderately in CG and TDW, and severely in TDG. TSW displayed increased baroreflex and high sugar intake returned it to CW. Sympathetic nerve activity increased and parasympathetic decreased in TDW but not TSW and these effects were exacerbated sharply in TDG and slightly in TSG. Arterial pressure and heart rate increased in all groups but to a lesser degree in TDG. Plasma aspartate aminotransferase increased in all groups except TSW, but the increase was nearly 3X greater in TDG vs. any other group. Creatine kinase-MB increased in all groups except TSG and was far greater in TD than other groups. Troponin-T and brain natriuretic peptide were greatly increased in TDG compared to all other groups. Thus, perinatal taurine depletion increases injury from cardiac ischemia/reperfusion, and in adult rats on a high sugar diet, these effects are greatly exacerbated.

Perinatal taurine exposure alters renal potassium excretion in adult conscious rats

Perinatal taurine exposure alters renal hemodynamics and sodium excretion in adult rats. This study further tests the effect of perinatal taurine on renal potassium excretion in adult conscious rats. Female Sprague‐Dawley rats were fed normal rat chow and given water alone (C), 3% beta‐alanine in water (taurine depletion, TD) or 3% taurine in water (taurine supplementation, TS), either from conception until delivery (fetal period; TDF or TSF) or from delivery until weaning (lactation period; TDL or TSL). In Experiment 1, after weaning, male offspring were fed normal rat chow and tap water. In Experiment 2, female pups were treated similarly, but from conception until weaning. At 7–8 weeks of age, renal potassium excretion at rest and after an acute saline load (5% of body weight) was studied in conscious, restrained rats. All male groups displayed similar renal potassium excretion. TSF increased fractional potassium excretion at rest but not in response to saline load, whereas TDF did the opposite. Plasma potassium levels were lower only at rest in TSF but at rest and during the challenge in TDF. Their glomerular filtration rates did not significantly different among groups. In female offspring, perinatal taurine supplementation decreased renal potassium excretion, glomerular filtration rate, and plasma potassium concentration at rest and after the saline load. It is unlikely that increased tubular reabsorption caused these effects, since the fractional potassium excretion significantly increased, especially at rest. Perinatal taurine depletion had no significant effect on renal potassium excretion in the female offspring. The present data suggest that perinatal taurine exposure influences renal potassium excretion in the adult rats.

Taurine protects the liver against lipid peroxidation and membrane disintegration during rat hepatocarcinogenesis.

The purpose of this study was to determine the effects of taurine supplementation on both hepatic morphological changes and the extent of hepatic lipid peroxidation and membrane disintegration during rat hepatocarcinogenesis. Sprague Dawley rats were fed high fat diets containing 15% corn oil and were maintained on drinking water with or without 1% taurine. Two weeks after the appropriate feeding regimen, hepatocarcinogenesis was induced by a modification of the Solt and Farber method. This involved a 8 week protocol, including diethylnitrosamine initiation, 3 weeks of 2-acetylaminofluorene feeding and finally a 70% partial hepatectomy. Morphological changes of the hepatocyte were observed by transmission electron microscopy (TEM). Hepatocytes of the carcinogen-treated rat not exposed to taurine contained normal nuclei, but the endoplasmic reticulum (ER) and the mitochondria (Mi) were almost destroyed. By contrast, although the hepatocytes from the taurine supplemented group contained some irregular contour nuclei, the ER and Mi were normal. In the carcinogen-treated groups, lipid peroxidation was decreased because of the activation of several detoxifying enzymes. Glutathione S-transferase (GST) activity increased in the carcinogen-treated groups but less so in the group supplemented with taurine before treatment with the carcinogen. In the group supplemented with taurine prior to treatment with the carcinogen, glutathione peroxidase (GPx) activity was higher than in the carcinogen-treated group lacking taurine exposure. Consistent with the severe destruction to the membrane in the carcinogen-treated rats, hepatic glucose-6-phosphatase (G6Pase) activity, an index of membrane stability, was also decreased. However, both the fall in G6Pase activity and the degree of membrane damage was reduced in the carcinogen-treated animals receiving oral taurine. These results suggest that taurine appears to inhibit lipid peroxidation, to alter the activity of the defense enzymes and to protect the liver against membrane disintegration during rat hepatocarcinogenesis.

Kinetic Mechanism of Na+ Channel Depression by Taurine in Guinea Pig Ventricular Myocytes

To examine effects of taurine on the kinetics of the Na+ channel current (INa), action potentials and whole-cell Na+ currents were recorded from single ventricular myocytes of guinea pigs. Kinetic parameters for the activation and inactivation of INa were determined in accordance with the first-order kinetic model. Changes in the kinetic parameters were assessed before and after taurine exposure (5–50 mM). While taurine at concentrations higher than 10 mM decreased the peak INa by ca. 15%, the agent did not alter the reversal potential and the maximum Na+ conductance (GNa). Taurine shifted the steady-state inactivation (hoo) curve toward the negative potential direction and decreased the slope of h∞. Concomitantly, the slope of the steady-state activation (moo) was also slightly decreased and the rate of inactivation in the large potential region (− 40 to −30 mV) slightly increased, whereas the rate of the activation appeared to remain unchanged. It is suggested that taurine alters the surface charge of the membrane and reduces the number of charges moving upon activation and inactivation of channels, thereby reducing INa.

Substrate-specific regulation of the taurine transporter in human placental choriocarcinoma cells (JAR)

Exposure of the JAR human placental choriocarcinoma cells to taurine leads to a marked decrease in the activity of the taurine transporter in these cells. The ability to induce this adaptive response is not unique to taurine but is shared by other substrates of the transporter as well. Compounds such as betaine and α-aminoisobutyric acid which are not substrates for the transporter do not produce this effect. The change in the taurine transporter activity induced by taurine exposure is however unique to the taurine transporter because the activities of many other transport systems remain unaffected under these conditions. The adaptive regulation is not associated with any change in the dependence of the transporter activity on Na + and Cl −, in the Na +/Cl −/taurine stoichiometry and in the affinities of the transporter for Na + and Cl −. The decrease in the transporter activity caused by taurine exposure is due to a decrease in the maximal velocity of the transporter, and to a lesser extent, in the substrate affinity of the transporter. The decrease in the transporter activity observed in intact cells is demonstrable in plasma membrane vesicles after isolation from control and taurine-exposed cells. Cycloheximide and actinomycin D block the adaptive response in intact cells to a significant extent, but not completely. Northern blot analysis of mRNA from control and taurine-exposed cells shows that taurine exposure causes a significant decrease in the steady state levels of the taurine transporter mRNA. It is concluded that the activity of the taurine transporter in JAR cells is subject to substrate-specific adaptive regulation and that transcriptional as well as posttranscriptional events are involved in this regulatory process.

Physiological actions of taurine

Physiological actions of taurine