Comparison of taurine-verapamil interaction in hamsters and rats

Taurine concentrations were determined in hearts and whole blood of female Syrian golden hamsters and Wistar rats following 30 days of drinking: (i) tap water, (ii) taurine solution or (iii) a taurine uptake inhibitor (GES). The groups were duplicated in animals receiving daily verapamil injections during the treatment period. Heart taurine increased with (ii) and decreased with (iii) in both species; blood taurine changed similarly in rats only. Verapamil enhanced taurine uptake and offset the GES inhibition in the hamster heart, but had no such effect in rats. Possible implications of the species differences are elaborated upon.     

Effects of taurine depletion on rat cardiac electrophysiology: in vivo and in vitro studies

Electrocardiograms were monitored in unanesthetized rats during treatment with drinking water containing guanidinoethyl sulfonate (GES), an inhibitor of taurine transport, which depleted cardiac taurine content. Treatment led to a selective prolongation of the QT interval which was highly correlated with the degree of taurine depletion (r2 = 0.92, p less than .001). Compared to controls, the duration of ventricular muscle action potentials was significantly increased in GES-treated rats, and this accounted for the prolongation of QT intervals. Oral taurine supplements reversed GES-induced cardiac taurine depletion and the associated increased duration of action potentials and QT intervals. In vitro superfusion with 0.2-10 mM GES or taurine had no effect on action potentials of control or GES-treated rats. These data indicate that intracellular taurine may play a role in regulating myocardial action potential duration, particularly during repolarization.     

Actions of guanidinoethane sulfonate on taurine concentration,retinal morphology and seizure threshold in the neonatal rat

Administration of the taurine transport inhibitor, guanidinoethane sulfonate (GES) to pregnant rats depleted taurine concentrations to approximately one-half of normal values in the newborn progeny. By 5 days of age taurine concentrations had returned to normal in all organs tested with the exception of the lungs. Longer postnatal exposure to GES significantly depressed tissue taurine levels. Prenatal exposure to GES had no effect on fetal development or the capability of the newborn rat to biosynthesize or transport taurine. Pre- and postnatal exposure to GES produced a degeneration of the photoreceptor layer of the retina similar to that observed in cats fed a taurine deficient diet. The pentylene tetrazole chemoshock threshold in GES-treated pups was greater than that in control pups. These results indicate that prenatal exposure to GES deplete taurine concentrations in the newborn rat. Morphological changes are thereby produced in the retina of rat that are similar to those observed in animals having limited ability to synthesize taurine which are maintained on a taurine-free diet.     

Comparative metabolism and taurine-depleting effects of guanidinoethanesulfonate in cats,mice, and guinea pigs

Guanidinoethanesulfonate (GES) is a competitive inhibitor of taurine transport. The ability of GES to deplete taurine content has been compared in three species representing omnivores, carnivores, and herbivores. Rats and mice given drinking water containing 1% GES showed large decreases in taurine concentration in all examined organs within a few days. These species do not metabolize GES. The substance was without effect on guinea pigs, a species that does not depend on diet for taurine, even after 20 days of treatment. However, guinea pigs metabolize a fraction of the GES administered to taurine. Cats responded to GES by increasing their urinary excretion of taurine 10-fold, while simultaneously maintaining normal concentrations in body organs. [1,2-³H]GES given orally to cats was extensively metabolized to radioactive taurine. It therefore appears that the cat and to a lesser extent, the guinea pig, have transamidinase or amidinohydrolase activity for which GES is a substrate. However, this substance rapidly depletes taurine levels in the omnivores studied, and promises to be useful in further investigations on taurine in these species.     

Polarized nature of taurine transport in LLC-PK1 and MDCK cells: Further characterization of divergent transport models

Summary Taurine transport was measured in cultured epithelial cells-LLC-PK1 and MDCK-grown on permeable membrane supports. Taurine transport by LLC-PK1 cells was greater on the apical surface compared to the basolateral surface. MDCK cells exhibited greater taurine uptake from the basolateral side. Transepithelial taurine flux was in the direction of apical to basolateral in the LLC-PK1 monolayers. There was no net transepithelial movement of taurine in the MDCK monolayers. Efflux of taurine from the apical and the basolateral membrane surfaces of LLC-PK1 cell monolayers was stimulated by external-alanine but not L-alanine. Efflux of taurine from MDCK cell monolayers was stimulated by-alanine on the basolateral surface. While the competitive inhibitor guainidinoeithane sulfonate (GES) competitively inhibited taurine uptake to a similar degree on the apical and basolateral surface of LLC-PK1 cell monolayers, GES had a more potent inhibitory effect on the basolateral taurine uptake in MDCK cells when compared to its inhibition of apical taurine transport. We conclude that there are characteristic differences in transport of taurine by apical and basolateral surfaces of LLC-PK1 and MDCK cells which may be the consequence of asymmetric distribution or unique structural properties of the taurine transporter.Supported by a grant from the National Institutes of Health (DK 37223), the American Heart Association (92-004470).     

Taurine depletion increases phosphorylation of a specific protein in the rat retina

Summary Partial depletion of the taurine content in the rat retina was accomplished for up to 22 weeks by introduction of 1.5% guanidinoethanesulfonate (GES) in the drinking water. Taurine levels decreased by 50% after 1 week of GES treatment and by 80% at 16 weeks. Replacement of GES by taurine to the GES-treated rats from week 16 to 22 returned their taurine content to the control value. Whereas addition of taurine (1.5%) to the drinking water of control rats from week 16 to 22 elevated the retinal taurine content to 118% of the control value, the administration of untreated water to GES-treated animals for the 16 to 22 week time period increased the retinal taurine content to only 76% of the control value.The amplitude of the electroretinogram (ERG) b-wave was decreased by 60% after GES-treatment for 16 weeks and maintained this reduced level for up to 22 weeks. Administration of taurine in the drinking water from week 16 to 22 returned the b-wave amplitude to a range not statistically different from the control values whereas the administration of untreated water produced less improvement.After 6 weeks of GES treatment when the retinal taurine content was reduced by 70% and the amplitude of the b-wave was reduced by 50% (extrapolated from Figure 1), phosphorylation of a specific protein with an approximate molecular weight of 20K was increased by 94%. The increased phosphorylation of the ~20K protein observed after GES treatment was reversed when the animals were treated with taurine (1 1/2%) in the drinking water for an additional 6 weeks. There was no change in the phosphorylation of the ~20K protein when animals were treated with taurine for 6 weeks. The data obtained support the theory that taurine may have a regulatory effect on retinal protein phosphorylation.     

Taurine-induced long-lasting potentiation in the rat hippocampus shows a partial dissociation from total hippocampal taurine content and independence from activation of known taurine transporters

Perfusion with high millimolar levels of taurine evoked a long-lasting potentiation (LLP-TAU) of synaptic transmission in the Schaffer-collateral CA1 region of the rat hippocampus. Although LLP-TAU showed some correlations to increases in the total taurine content of hippocampal slices, it could not be blocked by the taurine transport inhibitor guanidinoethanesulfonic acid (GES), which was able to significantly reduce total slice taurine uptake. Inhibition of GABA transport by either nipecotic acid or beta-guanidinopropionate failed to abolish LLP-TAU and had no significant effect on taurine uptake. The combination of GES and nipecotic acid also had no significant effect on LLP-TAU. Experiments with transportable structural analogs of taurine (beta-aminoisobutyric acid, homotaurine, and isethionic acid) suggest that activation of classical taurine transport pathways does not always yield a robust LLP-TAU. Hippocampal LLP-TAU could be significantly attenuated, however, by pre-incubation with submillimolar levels of taurine. In summary, the development of LLP-TAU in the rat hippocampus appears to be associated with the intracellular accumulation rather than the activation of known transporters of taurine, but the precise means of its accumulation remains to be identified.     

The effect of taurine supplementation on oxidative stress in experimental hypothyroidism

The purpose of this study was to investigate the oxidative status in experimental hypothyroidism and the antioxidant effect of taurine supplementation. Forty male Sprague Dawley rats were randomly divided into four groups (group 1, control; group 2, control + taurine; group 3, propylthiouracil (PTU); group 4, PTU + taurine). Hypothyroidism was induced by giving 0.05% PTU in drinking water for 8 weeks. Taurine was supplemented in drinking water at a concentration of 1% for 5 weeks. Plasma (p < 0.05), red blood cell (p < 0.01), liver (p < 0.001) and kidney tissue (p > 0.05) malondialdehyde levels were increased in the PTU group compared with those of the control rats and were decreased in the PTU + taurine group compared with the PTU alone group. No significant changes were observed in glutathione levels of kidney and liver in the PTU group, but taurine supplementation significantly increased the glutathione levels of these tissues. Paraoxonase and arylesterase activities were decreased in the PTU group while taurine supplementation caused no significant changes in paraoxonase and arylesterase activities. These findings suggest that taurine supplementation may play a protective role against the increased oxidative stress resulting from hypothyroidism.     

A Possible Interrelationship Between Extracellular Taurine and Phosphoethanolamine in the Hippocampus

The effect of guanidinoethane sulfonic acid (GES), an inhibitor of taurine uptake, was examined with respect to endogenous amino acids in the hippocampus of the freely moving rabbit. GES increased the extracellular levels of both taurine and phosphoethanolamine (PEA), other amino acids being unaffected. However, long-term oral administration of GES selectively reduced endogenous taurine levels. The effect of GES on PEA appeared to be a consequence of the elevated extracellular taurine as exogenously administered taurine per se increased PEA levels in the extracellular space. The findings are discussed in conjunction with the proposed membrane-stabilizing effects of taurine.     

Effects of Taurine on Nitric Oxide and 3-Nitrotyrosine Levels in Spleen During Endotoxemia

Taurine (2-aminoethanesulfonic acid) is a free sulfur-containing β-amino acid which has antioxidant, antiinflammatory and detoxificant properties. In the present study, the role of endotoxemia on peroxynitrite formation via 3-nitrotyrosine (3-NT) detection, and the possible antioxidant effect of taurine in lipopolysaccharide (LPS)-treated guinea pigs were aimed. 40 adult male guinea pigs were divided into four groups; control, endotoxemia, taurine and taurine+endotoxemia. Animals were administered taurine (300 mg/kg), LPS (4 mg/kg) or taurine plus LPS intraperitoneally. After 6 h of incubation, when highest blood levels of taurine and endotoxin were attained, the animals were sacrificed and spleen samples were collected. The amounts of 3-nitrotyrosine and taurine were measured by HPLC, and reactive nitrogen oxide species (NOx) which are stable end products of nitric oxide was measured spectrophotometrically in spleen tissues. LPS administration significantly decreased the concentration of taurine whilst increased levels of 3-NT and NOx compared with control group. It was determined that taurine treatment decreased the levels of 3-nitrotyrosine and NOx in taurine+endotoxemia group. The group in which taurine was administered alone, contradiction to well-known antioxidant effect, taurine caused elevated concentration of 3-NT and NOx. This data suggest that taurine protects spleen against oxidative damage in endotoxemic conditions. However, the effect of taurine is different when it is administered alone. In conclusion, taurine may act as an antioxidant during endotoxemia, and as a prooxidant in healthy subjects at this dose.     

The effect of taurine on cholesterol degradation in mice fed a high-cholesterol diet

The hypocholesterolemic effect of taurine was examined in mice fed a high-cholesterol diet containing 1% cholesterol and 0.25% sodium cholate. Male C57BL/6 mice were divided into 3 groups: control group (HC), 1% taurine-supplemented group (HCT+), and taurine-deficient group (HCT-) produced by supplying 0.5% guanidinoethyl sulfonate (GES) solution ad libitum instead of water. After they were fed with the respective diet or drinking water for 4 weeks, the liver taurine level was reduced 80% in the HCT- group compared with that in the HC group, although there was no difference in the serum taurine amount between the two groups. The formation ratio of cholesterol gallstones increased from 71% to 100% by taurine deficiency, and decreased to 0% by taurine supplementation. Compared with the HC group, serum and liver cholesterol significantly decreased, and the excretion of fecal bile acid notably rose in the HCT+ group but tended to lower in the HCT- group. There were no differences in LDL receptor protein level among the three groups. In the subsequent experiment, triglycerides (TG) secretion rate was determined and found to be significantly suppressed by taurine supplementation. In conclusion, it is suggested that taurine does not up-regulate LDL receptor protein level, and the decrease in cholesterol in the circulation is mainly due to its suppressive effect on TG secretion from the liver.     

Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride

Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.     

Transport, nutritional and metabolic studies of taurine in staphylococci

A specific, Na+-dependent, energy-requiring transport system for taurine has been reported recently in the Staphylococcus aureus M strain. Taurine was taken up vigorously by all S. aureus strains tested. The system was Na+-dependent, and Na+ decreased the Km but had no effect on the Vmax of the transport system. Among coagulase-negative staphylococci, the Staphylococcus epidermidis group (a taxonomically related group of species associated with humans or other primates) and the free-living, wide-ranging species Staphylococcus sciuri showed vigorous taurine uptake. Somewhat lower rates were found in the Staphylococcus saprophyticus group. Low or barely detectable uptake rates were noted in other staphylococcal species that were primarily of animal origin. No taurine uptake was detected in a variety of other bacterial species tested. Taurine uptake, which was not Na+-dependent, occurred in a Pseudomonas aeruginosa strain grown on taurine as sole energy, carbon, nitrogen, and sulphur source, but not when it was grown in a gluconate/salts medium. In nutritional studies we were unable to demonstrate a role for taurine as a sulphur source for S. aureus. [1,2-14C]- and [35S]taurine were taken up during overnight growth of cells, and radioactivity was distributed similarly among cellular fractions, indicating that the carbon and sulphur atoms of taurine were not cleaved and had the same fate. We were unable to demonstrate any catabolism of taurine in radiorespirometric experiments to detect evolution of 14CO2 by cells incubated with [1,2-14C]taurine. Thus, we found no evidence for a role of taurine in the energy, carbon and sulphur metabolism of S. aureus.     

Taurine: Protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats

Summary Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not to affect the urinary excretion of taurine (a non-invasive marker of liver damage), levels of serum and liver taurine were markedly raised in animals receiving alcohol + taurine compared to animals given taurine alone. The ethanol-inducible form of cytochrome P-450 (CYP2E1) was significantly induced by alcohol; the activity was significantly lower than controls and barely detectable in animals fed the liquid alcohol diet containing taurine. In addition, alcohol significantly increased homocysteine excretion into urine throughout the 28 day period of ethanol administration; however, taurine did not prevent this increase. There was evidence of slight cholestasis in animals treated with alcohol and alcohol + taurine, as indicated by raised serum bile acids and alkaline phosphatase (ALP). The protective effects of taurine were attributed to the potential of bile acids, especially taurine conjugated bile acids (taurocholic acid) to inhibit the activity of some microsomal enzymes (CYP2E1). Thesein vivo findings demonstrate for the first time that hepatic steatosis and lipid peroxidation, occurring as a result of chronic alcohol consumption, can be ameliorated by administration of taurine to rats.     

Taurine deficiency damages retinal neurones: cone photoreceptors and retinal ganglion cells

In 1970s, taurine deficiency was reported to induce photoreceptor degeneration in cats and rats. Recently, we found that taurine deficiency contributes to the retinal toxicity of vigabatrin, an antiepileptic drug. However, in this toxicity, retinal ganglion cells were degenerating in parallel to cone photoreceptors. The aim of this study was to re-assess a classic mouse model of taurine deficiency following a treatment with guanidoethane sulfonate (GES), a taurine transporter inhibitor to determine whether retinal ganglion cells are also affected. GES treatment induced a significant reduction in the taurine plasma levels and a lower weight increase. At the functional level, photopic electroretinograms were reduced indicating a dysfunction in the cone pathway. A change in the autofluorescence appearance of the eye fundus was explained on histological sections by an increased autofluorescence of the retinal pigment epithelium. Although the general morphology of the retina was not affected, cell damages were indicated by the general increase in glial fibrillary acidic protein expression. When cell quantification was achieved on retinal sections, the number of outer/inner segments of cone photoreceptors was reduced (20?%) as the number of retinal ganglion cells (19?%). An abnormal synaptic plasticity of rod bipolar cell dendrites was also observed in GES-treated mice. These results indicate that taurine deficiency can not only lead to photoreceptor degeneration but also to retinal ganglion cell loss. Cone photoreceptors and retinal ganglion cells appear as the most sensitive cells to taurine deficiency. These results may explain the recent therapeutic interest of taurine in retinal degenerative pathologies.     

The transport,biosynthesis and biochemical actions of taurine in a genetic epilepsy

We have investigated the transport, biosynthesis and turnover of taurine in genetically seizure-susceptible (SS) and seizure-resistant (SR) rats. In SS rats, the rate of taurine uptake into the brain was half the rate in SR rats. As no difference was found in biosynthesis of taurine, these results imply a slower turnover of taurine in SS brain.The effect of taurine on the decarboxylation of glutamate in brain homogenates was determined. In homogenates of SR brains, taurine had no effect but in SS preparations taurine increased the rate of decarboxylation by 20%. Increased decarboxylation of glutamate may be one basis for the prolonged anticonvulsant action of taurine in the SS rat.     

Hypolipidemic action of taurine in rats.

The effect of taurine on the serum and liver cholesterol and triglyceride levels was studied in rats fed cholesterol plus cholic acid. Four groups of 4 weeks old rats were fed control diet, hypercholesterolemic diet (HCD), HCD + 1% taurine or HCD + 2% taurine for 8 weeks. Addition of taurine in HCD diet showed a significant reduction not only in serum total cholesterol and triglyceride levels but also in liver total cholesterol, lipid and triglyceride contents compared to the animals fed HCD alone. Histological examination of organs of these animals showed severe fatty vacuolation in livers and signet ring type vacuolation in kidneys of rats fed HCD. Taurine showed ameliorating effect on these abnormalities. The animals fed taurine in HCD also showed increased bile and sterol excretion in faeces compared to rats fed HCD alone. Taurine showed significant hypocholesterolemia in rats probably by enhancing the catabolism of cholesterol and reducing the absorption of dietary cholesterol.     

Effects of cardioactive drugs on the beating activity of myocardial cell cultures isolated from offspring of trained and untrained pregant rats

Summary Primary cultures of beating myocardial cells were obtained from 5-d-old offspring of trained (T) and untrained (UT), pregnant, Sprague-Dawley rats. The myocardial cells from the T and UT groups were evaluated for their beating responses to three cardioactive drugs: verapamil (V), isoproterenol (ISO), and propranolol (PRO). The myocardial cell cultures from the UT group showed complete loss of beating when the calcium (Ca⁺⁺) antagonist, V, was added to the cultures for 1 h or more; the T group was able to show some beating at comparable concentrations and durations of exposure with V. The beta agonist, ISO, markedly stimulated the beating rate of both the T and UT groups, but the beating rates were higher in the UT group at comparable concentrations and durations of exposure than with the T group. When the cultures were pretreated with the beta blocker, PRO, before treatment with ISO, a concentration inhibitory effect on the beating rate was observed in both groups. However, the T cultures were more sensitive to the inhibitory effects of PRO. These results demonstrate that primary cultures of rat myocardial cells isolated from the offspring of trained and untrained pregnant rats show differential beating responses to three well-known cardioactive drugs. This study was supported by grants from the American Heart Association, Texas Affiliate, and the University of Texas Research Institute.     

The effect of taurine depletion with guanidinoethanesulfonate on bile acid metabolism in the rat

Administration of guanidinoethanesulfonate (GES) to male rats for 5 weeks resulted in a 90% decrease in the hepatic taurine concentration. This depletion of hepatic taurine was associated with a 570% increase in the concentration of glycine-conjugated bile acids, a 30% decrease in the concentration of taurine-conjugated bile acids, and an increase in the ratio of glycine- to taurine-conjugated bile acids from 0.046 to 0.45. The total concentration of bile salts in the bile and the turnover of cholic acid were not affected by administration of GES. The data indicate that the taurine-depleted rat conserves taurine to some extent by using glycine instead of taurine for bile salt synthesis but not by decreasing the daily fractional turnover of bile acids.