Myocardial taurine,development and vulnerability to ischemia

Summary. Depleting intracellular taurine in heart cells improves their resistance to ischemia and reperfusion injury. The aim of this work was to see whether physiologically low levels of endogenous taurine also reflect a reduced vulnerability of the myocardium to cardiac insults. The myocardial concentration of taurine was measured during different stages of development and compared with vulnerability to ischemia and reperfusion injury in the rat and in pediatric patients undergoing cardiac surgery.Rat hearts with relatively lower levels of taurine were significantly more resistant to an ischemic inult and there was a strong negative correlation between taurine content and recovery. Childrens hearts had significantly lower taurine levels compared to infants hearts which was consistent with their known increased resistance to an ischemic cardioplegic insult (Imura et al., 2001). This work shows that the changes in the concentration of myocardial taurine during development correlate with vulnerability to ischemia where low myocardial taurine is associated with improved recovery upon reperfusion.     

The effect of taurine administration on vitamin C levels of several tissues in mice

Summary. Taurine (2-aminoethane sulphonic acid), a sulphur-containing beta amino acid, is the most prevalent free intracellular amino acid in many human and animal tissues. Vitamin C metabolism is also fluenced by sulphur-containing amino acids. The aim of this study is to investigate the effect of taurine administration on the vitamin C levels of plasma and several tissues (brain, liver, kidneys) in mice with incisional skin wounds. Animals were divided into two as control and taurine groups. Taurine was freshly dissolved in sterile saline and administered daily (60µl, ip) for five days in the taurine group. At the end of the fifth day, the animals were killed by decapitation. The brain, liver and kidneys were immediately removed. Vitamin C levels were measured in plasma and several tissues. The administration of taurine had no effect on the plasma vitamin C levels (P>0.05) but significantly increased in liver and kidneys (P<0.001). In conclusion, taurine may affect the vitamin C metabolism in tissues by different mechanisms.     

Effects of taurine in glucose and taurine administration

Summary. Taurine has several biological processes such as hypoglycemic action, antioxidation, detoxification, etc. To assess the effect of taurine administration on the guinea pigs with hyperglycemia, blood glucose, C-peptide levels together with morphologic alterations in the pancreatic ultrastructure were investigated in terms of hypoglycemic action and malondialdehyde and total sulfhydryl group levels with regard to oxidation-antioxidation relation. Animals were divided into four groups of six. Glucose supplementation group was administrated a single dose of glucose (400mg/kg, i.p.) injection. Glucose and taurine supplementation group was administrated glucose treatment (a single dose, 400mg/kg, i.p.) following taurine (a single dose, 200mg/kg, i.p.). Taurine and glucose supplementation group was administered taurine treatment (a single dose, 200mg/kg, i.p.) following glucose treatment (a single dose, 400mg/kg, i.p.). Control animals received no treatment. Blood samples were collected at the end of the experiments for the determination of glucose, C-peptide (indicator of insulin secretion), lipid peroxidation (thiobarbituric acid reactive substances), and total sulfhydryl groups levels. Pancreatic tissue samples were then collected and processed for transmission electron microscopy. The findings showed that glucose supplementation following taurine administration significantly decreased blood glucose level by increasing C-peptide level and the pancreatic secretion stimulated morphologically and insignificantly changed thiobarbituric acid reactive substances and total sulfhydryl group levels. These observations suggest that taurine administration may be useful in hyperglycemia because of its hypoglycemic and protective effects.     

Taurine protected myocardial mitochondria injury induced by hyperhomocysteinemia in rats

Summary. Taurine can protect against cardiovascular diseases, whereas elevated levels of plasma homocysteine are associated with atherosclerotic and thromboembolic cardiovascular diseases. To illustrate the effects of taurine on hyperhomocysteinemia, we observed the myocardial mitochondria dysfunction in the rats with hyperhomocysteinemia induced by diet methionine loading, and the therapeutic effect of taurine. A methionine diet increased plasma homocysteine concentration (133.51±27.91mol/L vs 12.31±2.58mol/L in control, P<0.01), stimulated the production of reactive oxygen species (ROS) in the myocardial mitochondria, and inhibited the activities of mitochondrial Mn-superoxide dismutase and catalase. The ⁴⁵Ca uptake and Ca²⁺-ATPase activity in the myocardial mitochondria were significantly lowered in rats with hyperhomocysteinemia. Taurine supplements effectively attenuated the hyperhomocysteinemia-induced ROS production and inhibition of Mn-superoxide dismutase and catalase activities in the myocardial mitochondria, and increased its ⁴⁵Ca uptake and Ca²⁺-ATPase activity. Thus, taurine antagonizes the oxidative stress injury in the myocardial mitochondria induced by the hyperhomocysteinemia.     

Ethanol but not acetaldehyde induced changes in brain taurine: a microdialysis study

Summary. Research has suggested that catalase plays a role in mediating ethanols psychopharmacological effects. Catalase is an enzyme that oxidizes ethanol to acetaldehyde. It has been reported that when catalase activity is reduced by 3-amino-1,2,4-triazole (AT), rats reduce their intake and preference for ethanol. The present study assessed the effects of AT on the brain amino acids levels following ethanol administration in Wistar rats. The study consisted of three parts. In the first part, we found no effects of acute and chronic intraperitoneally administered acetaldehyde on amino acids dialysate levels in nucleus accumbens. In the second part, AT was administered five hours prior to ethanol or its vehicle. Ethanol significantly affected the levels of taurine in rat pre-treated with AT. In the final part, ethanol was administered following the pre-treatment with AT but the dependent variable was the concentration of ethanol in the brain.     

Taurine chloramine and taurine bromamine induce heme oxygenase-1 in resting and LPS-stimulated J774.2 macrophages

Summary. Taurine chloramine (TauCl) and taurine bromamine (TauBr) are products of activated neutrophils and eosinophils, respectively. It has been reported that TauCl, has strong anti-inflammatory properties. In a number of separate studies it has been shown that heme oxygenase-1 (HO-1), a stress inducible protein, exerts similar anti-inflammatory effects. In this study we investigated the influence of HO-1 on TauCl/TauBr mediated suppression of NO generation in J774.2 macrophages. Expression of HO-1 and inducible nitric oxide synthase (NOS-2) in LPS stimulated J774.2 cells provides an opportunity for determining these interactions. TauCl and TauBr, at non-cytotoxic concentrations, in a similar, dose-dependent manner, inhibited the expression of NOS-2, as evidenced by western blotting technique. Surprisingly, TauCl and TauBr induced expression of HO-1 in both non-activated and LPS-activated macrophages. Importantly, the fall in NOS-2 protein level was associated with a concomitant, dose-dependent induction of HO-1. In addition, an inhibitor of HO-1 activity, chromium III mesoporhyrin (CrMP), attenuated the inhibitory activity of TauBr but not that of TauCl, as measured by nitrite accumulation. These results suggest that at a site of inflammation, TauCl and TauBr may provide a link between taurine-dependent and HO-1-dependent cytoprotective mechanisms.     

Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects

Summary. Taurine has beneficial effects on lipid metabolism in experimental animals fed with high-cholesterol or high fat diets. Whether taurine benefits lipid metabolism in humans has rarely been investigated. The aim of this study was to evaluate the effects of taurine on serum lipids in overweight or obese young adults. Thirty college students (age: 20.3±1.7 years) with a body mass index (BMI) 25.0kg/m², and with no evidence of diabetes mellitus were selected and assigned to either the taurine group (n=15) or the placebo group (n=15) by double-blind randomization. Taurine 3g/day or placebo was taken orally for 7 weeks. Triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and plasma glucose were measured before and after supplementation. The atherogenic index (AI) was calculated as (TC–HDL-C)/HDL-C. There were no differences in any baseline parameter between the two groups. Taurine supplementation decreased TG and AI significantly. Body weight also reduced significantly in the taurine group. These results suggest that taurine produces a beneficial effect on lipid metabolism and may have an important role in cardiovascular disease prevention in overweight or obese subjects.     

Hoe 140 abolishes the blood pressure lowering effect of taurine in high fructose-fed rats

Summary. High fructose feeding induces moderate increases in blood pressure of normal rats, associated with hyperinsulinemia, insulin resistance and impaired glucose tolerance. Increased vascular resistance, and sodium retention have been proposed to contribute to the blood pressure elevation in this model. Taurine, a sulphur-containing amino acid has been reported to have antihypertensive and antinatriuretic actions. In addition, taurine is shown to increase the excretion of nitrite and kinin availability and hence would be expected to improve the vascular tone. In the present study, the involvement of kinins in the blood pressure lowering effect of taurine was investigated by coadministration of Hoe 140, a kinin B₂ receptor antagonist along with taurine. The effects of taurine on plasma and urinary concentrations of sodium and tissue kallikrein activity were studied in high fructose-fed rats. Fructose-fed rats had elevated blood pressure and decreased levels of sodium in urine. Treatment with 2% taurine in drinking water prevented the blood pressure elevation and coadministration of Hoe 140 abolished this effect of taurine in high fructose-fed rats. The findings confirm the antinatriuretic action of taurine and also suggest a role for the kinins in the mechanism of taurine action in diet-induced hypertension.     

Role of taurine supplementation to prevent exercise-induced oxidative stress in healthy young men

Summary. To evaluate the protective effects of taurine supplementation on exercise-induced oxidative stress and exercise performance, eleven men aged 18–20 years were selected to participate in two identical bicycle ergometer exercises until exhaustion. Single cell gel assay (SCG assay) was used to study DNA damage in white blood cells (WBC). Pre-supplementation of taurine, a significant negative correlation was found between plasma taurine concentration before exercise and plasma thiobaribituric-acid reactive substance (TBARS) 6hr after exercise (r=–0.642, p<0.05). WBC showed a significant increase in DNA strand breakage 6hr and 24hr after exercise. Seven-day taurine supplementation reduced serum TBARS before exercise (p<0.05) and resulted in a significantly reduced DNA migration 24hr after exercise (p<0.01). Significant increases were also found in VO₂max, exercise time to exhaustion and maximal workload in test with taurine supplementation (p<0.05). After supplementation, the change in taurine concentration showed positive correlations with the changes in exercise time to exhaustion and maximal workload. The results suggest that taurine may attenuate exercise-induced DNA damage and enhance the capacity of exercise due to its cellular protective properties.     

Betaine or taurine administration prevents fibrosis and lipid peroxidation induced by rat liver by ethanol plus carbon tetrachloride intoxication

Summary. The aim of this study was to investigate the effect of betaine or taurine on liver fibrogenesis and lipid peroxidation in rats. Fibrosis was induced by treatment of rats with drinking water containing 5% ethanol and CCl₄ (2×weekly, 0.2ml/kg, i.p.) for 4 weeks. Ethanol plus CCl₄ treatment caused increased lipid peroxidation and disturbed antioxidant system in the liver. Histopathological findings suggested that the development of liver fibrosis was prevented in rats treated with betaine or taurine (1% v/v in drinking water) together with ethanol plus CCl₄ for 4 weeks. When hepatic taurine content was depleted with -alanine (3% v/v in drinking water), portal-central fibrosis induced by ethanol+CCl₄ treatment was observed to proceed cirrhotic structure. Betaine or taurine was also found to decrease serum transaminase activities and hepatic lipid peroxidation without any change in hepatic antioxidant system in rats with hepatic fibrosis. In conclusion, the administration of betaine or taurine prevented the development of liver fibrosis probably associated with decreased oxidative stress.     

Long-term taurine supplementation reduces mortality rate in streptozotocin-induced diabetic rats

Summary. Oxidative stress is implicated in the pathogenesis of diabetes mellitus. Taurine and vitamin E+selenium supplementation has some benefits in experimental models of diabetes mellitus. This study evaluates whether taurine and vitamin E+selenium supplementations reduce a hard end-point such as mortality due to diabetes. Streptozotocin-induced diabetic rats were fed with standard diet or taurine (5%, w/w) or vitamin E (500UI/Kg)+selenium (8mg/Kg) enriched diets. Taurine significantly decreased mortality rate (p<0.04), while vitamin E failed to increase survival. In the late phase of the disease, taurine significantly decreased glycaemia, being vitamin E ineffective. No correlation between glycaemia and survival was found. None of supplementations modified body weight. Thus, only taurine decreases the mortality rate and glycaemia. These results encourage new research in the field, since classical hypoglycaemic agents are unable to decrease mortality in diabetic patients.     

Optimal and effective oral dose of taurine to prolong exercise performance in rat

Summary. The aim of this study was to determine the effective and optimum dose of taurine for exercise performance and to maintain tissue taurine concentration. Rats received a respective daily dose of 0, 20, 100, and 500mg/kg body weight of taurine (EC and ET-1, -2, -3 groups, respectively) for two weeks, and then, were subjected to treadmill until exhaustion. The running time to exhaustion was significantly prolonged by 25% and 50% in the ET-2 and -3 groups, respectively, compared to that in the EC group accompanied with maintenance of taurine tissue concentrations. Furthermore, the oxidative glutathione per total glutathione ratio in tissues was inhibited in the ET-2 and -3 groups whereas it was higher in the EC group than in both the no exercise and taurine-administered groups. Therefore the effective and optimal doses of oral taurine administration for two weeks on a transient exercise performance were between 100 and 500mg/kg/day.     

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

Summary. 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±5.1M. 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.     

Effects of taurine supplementation on VDT work induced visual stress

Summary. In order to evaluate the effects of dietary taurine supplementation on visual fatigue induced by visual display terminals (VDT) work, 25 male college students aged from 20 to 24 years who were not engaged in VDT work were selected to participate in the study. Volunteers were randomly assigned to either the taurine supplementation (n=13) or the placebo supplementation control group (n=12). Before and after 12 days of taurine (3g/day) or placebo supplementation, two identical 2.5-hr VDT work tests were performed while recording the P100, N75 and N145 latencies and P100 amplitude of pattern visual evoked potential (PVEP) and the frequency of critical flicker fusion (CFF). Following 2.5-hr of VDT work, the P100 and N75 latencies of PVEP increased (P<0.01) while the P100 amplitude decreased significantly (P<0.01). The frequency of CFF also reduced significantly (P<0.01). After 12 days of taurine supplementation, the reduction in P100 amplitude after VDT work alleviated significantly (P<0.05). The results suggest that taurine supplementation alleviates visual fatigue induced by VDT work.     

Protective effect of taurine on the detachment of cultured cardiac fibroblasts from the substratum induced by calcium depletion

Summary. Removal of Ca²⁺ from the incubation medium of cultured rat cardiac fibroblasts causes cellular morphological changes, such as the formation of blebs, the ballooning of the cell membrane and the detachment from the culture dish. A 24hr preincubation with 20mM taurine blocked the Ca²⁺ depletion-induced detachment of the cardiac fibroblasts. However, taurine treatment did not prevent other morphological changes induced by Ca²⁺ depletion. The data suggest that taurine plays an important role in cell adhesion in the heart.     

Effects of culture conditions on taurine uptake by various variants of human endometrial carcinoma cells in culture

Summary. The general properties of the taurine uptake in human endometrial tumoral Ishikawa cells were similar to those usually found in other tissues. Uptake was notably affected by the oxygen pressure, being higher at the physiological pO₂ of the endometrium (40mm Hg, equivalent to 5% O₂) compared to that used under standard experimental culture conditions (160mm Hg or 20% O₂). Uptake of taurine was also density-dependent in Ishikawa cells and was significantly decreased at confluence. Uptake regulation by PKC driven phosphorylation occurs only in growing cells and not in resting cells. The taurine uptake of three Ishikawa cell lines was very different. The taurine uptake of one of the cell lines was affected by estradiol, probably through a non-genomic pathway, whereas tamoxifen had no effect in all cell lines.     

Augmented taurine release is not the mechanism of ischemic preconditioning’s cardioprotection

Summary. In ischemic preconditioning (IPC) a brief ischemic period protects the heart from a subsequent ischemic insult by an unknown mechanism. Osmotic swelling has been proposed to be a major cause of cell death when ischemic tissue is reperfused. The present study tests whether the preconditioned heart during reperfusion might release more taurine, an important osmolyte in the cardiac myocytes, to decrease cellular osmolarity, oppose swelling, and preserve viability. We collected the coronary effluent from isolated rabbit hearts for 10min before and 10min after preconditioning with 5min of global ischemia. The heart then experienced 15min of global ischemia and effluent was collected during reperfusion for 40min. A control group was studied similarly but without the preconditioning ischemia. Fifteen min of ischemia was chosen to avoid any taurine release caused by ischemic cell death. Taurine was measured with HPLC. In the IPC group there was a postischemic release over baseline of 5.09±1.51mol (approx 3.3% of the total taurine pool), whereas in the control group the release was not significantly different, 5.72±1.67mol. The percent of the taurine pool lost from each heart during reperfusion was calculated based on an assumption of a total content of 20M taurine/gm wet weight. Since the amount of taurine released by the isolated rabbit heart following ischemia was not different in preconditioned and non-preconditioned hearts, we conclude that reduced swelling through taurine release is not the mechanism of the cardioprotective effects of IPC.     

Characteristics of taurine release induced by free radicals in mouse hippocampal slices

Summary. The release of the inhibitory neuromodulator taurine in the hippocampus is markedly enhanced under various neural cell-damaging conditions, including ischemia and exposure to free radicals. The properties and regulation of the release evoked by a medium containing free radicals was investigated in hippocampal slices from adult (3-month-old) and developing (7-day-old) mice, using a superfusion system. The free radical damage was induced by applying 0.01% H₂O₂. The release of [³H]taurine was in both adult and developing hippocampus partly Ca²⁺-independent, mediated by Na⁺-dependent transporters and probably resulting from disruption of cell membranes and subsequent ion imbalance. The release in developing mice appeared to be more susceptible to regulation than that in adults, the stimulation by free radicals being in the latter already maximal. The release was reduced by adenosine A₁ receptor agonist R(–)N⁶-(2-phenylisopropyl)adenosine, which effect was, however, abolished by the antagonist 8-cyclopentyl-1,3-dipropylxanthine only in the immature hippocampus, indicating a receptor-mediated process. Moreover, the evoked taurine release in developing mice was potentiated by the ionotropic glutamate receptor agonists N-methyl-D-aspartate, kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate in a receptor-mediated manner, since the effects were abolished by their respective antagonists. The metabotropic glutamate receptors are of only minor significance in the release, the agonists of group I and II receptors slightly reducing the release. Furthermore, NO may also be involved in this release, the NO-generating compounds hydroxylamine and S-nitroso-N-acetylpenicillamine being able to enhance the free-radical-evoked release. It seems that the free-radical-stimulated release, potentiated by ionotropic glutamate receptor activation and NO production, could constitute part of the neuroprotective properties of taurine, being important particularly in the developing hippocampus and hence preventing excitotoxicity.     

The effect of taurine on renal ischemia/reperfusion injury

Summary. Ischemia-reperfusion (I/R) injury is one of the most common causes of renal dysfunction. Taurine is an endogenous antioxidant and a membrane-stabilizing, intracellular, free beta-amino acid. It has been demonstrated to have protective effects against I/R injuries to tissues other than kidney. The aim of this study was to determine whether taurine has a beneficial role in renal I/R injury. Forty Wistar-Albino rats were allocated into four groups as follows: sham, taurine, I/R, and I/R + taurine. Taurine 7.5 mg/kg was given intra-peritoneally to rats in the groups taurine and I/R + taurine. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to measure 1) serum levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and glutathione reductase (GSH-red); 3) renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine administration reduced I/R-induced increases in serum BUN and creatinine, and serum and tissue MDA levels (p < 0.05). Additionally, taurine lessened the reductions in serum and tissue glutathione levels secondary to I/R (p < 0.05). Taurine also attenuated histopathologic evidence of renal injury, and reduced I/R-induced P-selectin immunoreactivity (p < 0.05). Overall, then, taurine administration appears to reduce the injurious effects of I/R on kidney.     

Taurine concentration in the brain and in the plasma following intraperitoneal injections

Summary. The effect of different taurine doses (0.050, 0.125, 0.250, 0.500 and 1.000g/kg) administered intraperitoneally to Wistar rats was studied in both the plasma and the hippocampal microdialysate content.The samples were analyzed by reverse phased HPLC for the microdialysate samples and by HPLC with ion-exchange post-column derivatization (ninhydrin) for the plasma samples.In both plasma and microdialysate, we observed a dose dependent increase of taurine concentration. The AUC curves obtained from both microdialysate and plasma samples showed that the increase of taurine concentrations were linear. The mean ratio between AUCs microdialysate and plasma was 1.63±0.21 showing thus an unbalance between plasma and brain taurine content; a mechanism which enhance taurine transfer from the plasma to the brain was assumed.