Abstract: Introduction The present study was designed to investigate whether taurine mitigates fructose-induced oxidative stress in rat tissues such as heart and kidney. Methods Male Wistar rats of body weight 170-190 g were divided into four groups containing six rats each. Control animals received the control diet containing starch while fructose-fed animals received a fructose-enriched diet (greater than 60 percent of total calories). Fructose and taurine rats received the fructose diet and two percent taurine solution to drink. Control and taurine rats received the control diet and two percent taurine solution. After the treatment period of 30 days, insulin resistance index, by homeostasis model assessment (HOMA) was determined. The levels of lipid peroxidation markers, the enzymatic and non-enzymatic antioxidants status in heart and kidney tissues were measured. Results Fructose rats showed high values of HOMA, increased lipid peroxidation and impaired antioxidant status. Taurine treatment to fructose rats attenuated the increased lipid peroxidation, enhanced the levels of antioxidants and improved insulin sensitivity. Conclusion Inhibition of peroxidation markers and upregulation of antioxidant activity in rat tissues by taurine signify the potential utility of taurine as an adjunct in treatment of insulin resistance.

Abstract: Background: Neonates receiving parenteral nutrition (PN) are at risk for PN-associated cholestasis (PNAC); however, no preventive factors for PNAC have been clearly identified. Despite reports suggesting that taurine may prevent PNAC in neonates, such an effect of taurine has not yet been definitively demonstrated. We determined whether taurine supplementation reduces the incidence of PNAC in premature or critically ill neonates. Methods: This study was part of a prospective, randomized, multi-institutional trial designed to assess cholecystokinin vs placebo as a potential preventive therapy of PNAC. Taurine supplementation of PN varied between institutions. The presence or absence of taurine in PN was analyzed by multivariate analysis, with a primary outcome measure of serum conjugated bilirubin (CB) as a measure of PNAC. Results: Taurine reduced PNAC in premature infants (estimated maximum CB [95% confidence interval] 0.50 mg/dL [–0.17 to 1.18] for those receiving taurine, vs 3.45 mg/dL [1.79–5.11] for ...

Abstract: An experimental animal model of Huntington's disease (HD) phenotype was induced using the mycotoxin 3-nitopropionic acid (3-NP) and was well characterized behaviorally, neurochemically, morphometrically and histologically. Administration of 3-NP caused a reduction in prepulse inhibition (PPI) of acoustic startle response, locomotor hyper- and/or hypoactivity, bilateral striatal lesions, brain oxidative stress, and decreased striatal γ-aminobutyric acid (GABA) levels. Taurine is a semi-essential β-amino acid that was demonstrated to have both antioxidant and GABA-A agonistic activity. In this study, treatment with taurine (200 mg/kg daily for 3 days) prior to 3-NP administration reversed both reduced PPI response and locomotor hypoactivity caused by 3-NP injection. Taurine pretreatment also caused about 2-fold increase in GABA concentration compared to 3-NP-treated animals. In addition, taurine demonstrated antioxidant activity against oxidative stress induced by 3-NP administration as evidenced by the reduced striatal malondialdehyde (MDA) and elevated striatal glutathione (GSH) levels. Histochemical examination of striatal tissue showed that prior administration of taurine ahead of 3-NP challenge significantly increased succinate dehydrogenase (SDH) activity compared to 3-NP-treated animals. Histopathological examination further affirmed the neuroprotective effect of taurine in 3-NP-induced HD in rats. Taken together, one may conclude that taurine has neuroprotective role in the current HD paradigm due, at least partly, to its indirect antioxidant effect and GABA agonistic action.

Abstract: Experiments have shown that chronic nicotine administration caused oxidative damage in various organs by increasing lipid peroxidation products and decreasing the activity of endogenous antioxidants. The aim of this study was to investigate the effects of taurine treatment on nicotine-induced oxidative changes in rat thoracic aorta and heart and to explore the possible mechanisms of action. Male Wistar albino rats (200-250 g) were injected with nicotine hydrogen bitartrate (0.6 mg/kg; i.p.) or saline for 21 days. Taurine was administered (50 mg/kg; i.p.) alone or along with nicotine injections. After decapitation, the thoracic aorta and heart tissues were excised. The aorta was used for in vitro contractility studies or stored along with the heart samples for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Tissue samples were also examined histologically. Serum samples were stored for the measurement of MDA, GSH and lactate dehydrogenase (LDH) activity. Chronic nicotine treatment impaired both the contraction and relaxation responses of the aortic rings to phenylephrine and acetylcholine, respectively. It increased lipid peroxidation, MPO levels and tissue collagen content of both aorta and heart samples. Taurine supplementation to nicotine-treated animals reversed the contractile dysfunction and restored the endogenous GSH levels and decreased high lipid peroxidation and MPO activities in both tissues. These data suggest that taurine supplementation effectively attenuates the oxidative damage because of chronic nicotine administration possibly by its antioxidant effects.

Abstract: Background Preservation and ischemia-reperfusion injury still impact the outcome of orthotopic liver transplantation The authors used microdialysis with a view to monitoring its effect on graft function Methods A microdialysis catheter was inserted into the graft immediately after reperfusion and perfused with an isotonic solution for 48 hr Metabolites of the ischemia-reperfusion injury and selected amino acids were studied There were 18 patients, with a median age of 52 years (range, 38-62 years), 8 of whom were men Lactate, pyruvate, glycerol, and glucose levels were measured In addition, alanine, arginine, citrulline, γ-aminobutyric acid (GABA), glutamate, glutamine, glycine, and taurine were determined Results All grafts functioned well High lactate, pyruvate, and glycerol levels were observed in the immediate postoperative period These showed a significant rapid decrease and stabilized to baseline levels Alanine, glutamate, GABA, and taurine levels declined significantly to baseline values Arginine levels were low immediately postreperfusion and then increased, reaching significantly higher values beyond 19 hr Conclusions These data may represent normal changes seen in the immediate posttransplant period because all grafts functioned well Two important metabolic fates of arginine in the liver are in the detoxification of ammonia by means of the urea cycle, and in the synthesis of nitric oxide (NO) Low extracellular arginine may reflect influx of the amino acid into hepatocytes, resulting in formation of NO in the presence of inducible NO synthase or conversion to ornithine in the presence of arginase in the urea cycle As the organ stabilizes, restriction of arginine uptake may give rise to the observed increase in extracellular arginine

Abstract: Cystamine is beneficial to Huntington disease (HD) transgenic mice. To elucidate the mechanism, cystamine metabolites were determined in brain and plasma of cystamine-treated mice. A major route for cystamine metabolism is thought to be: cystamine --> cysteamine --> hypotaurine --> taurine. Here we describe an HPLC system with coulometric detection that can rapidly measure underivatized cystamine, cysteamine and hypotaurine, as well as cysteine and glutathione in the same deproteinized tissue sample. A method is also described for the coulometric estimation of taurine as its isoindole-sulfonate derivative. Using this new methodology we showed that cystamine and cysteamine are undetectable (< or = 0.2 nmol/100 mg protein) in the brains of 3-month-old HD transgenic (YAC128) mice (or their wild-type littermates) treated daily for 2 weeks with cystamine (225 mg/kg) in their drinking water. No significant changes were observed in brain glutathione and taurine but significant increases were observed in brain cysteine. Cystamine and cysteamine were not detected in the plasma of YAC128 mice treated daily with cystamine between the ages of 4 and 12 or 7 and 12 months. These findings suggest that cystamine is not directly involved in mitigating HD but that increased brain cysteine or uncharacterized sulfur metabolites may be responsible.

Abstract: Previously, we showed that treatment with resuscitative, post-ischaemic mild hypothermia (34 degrees C for 2 h) reduced apoptosis in the penumbra (cortex), but not in the core (striatum) of an endothelin-1 (Et-1)-induced focal cerebral infarct in the anaesthetized rat Therefore, the purpose of this study was to investigate by which pathways resuscitative mild hypothermia exerts its neuroprotective effect in this model The amino acids glutamate, serine, glutamine, alanine, taurine, arginine and the NO-related compound citrulline were sampled from the striatum and cortex of the ischaemic hemisphere using in vivo microdialysis The in vivo salicylate trapping method was applied for monitoring hydroxyl radical formation via 2,3 dihydroxybenzoic acid (2,3 DHBA) detection Caspase-3, neuronal nitric oxide synthase (nNOS) immunoreactivity and the volume of ischaemic damage were determined 24 h after the insult In both the striatum and the cortex, Et-1-induced increases in glutamate, taurine and alanine were refractory to mild hypothermia However, mild hypothermia significantly attenuated the ischaemia-induced 2,3 DHBA levels and the nNOS immunoreactivity in the cortex, but not in the striatum These observations were associated with a decreased caspase-3 immunoreactivity These results suggest that mild hypothermia exerts its neuroprotective effect in the penumbra partially by reducing nNOS activity and thereby preventing oxidative stress Furthermore, we confirm our previous findings that the neuroprotective effect of resuscitative hypothermia is not mediated by changes in ischaemia-induced amino acid release as they could not be associated with the ischaemia-induced damage in the Et-1 rat model

Abstract: Several studies demonstrate that taurine treatment prevents tissue damage in various models of inflammation. Experiments have shown that chronic nicotine administration caused oxidant damage in various organs by increasing lipid peroxidation products and decreasing the activity of endogenous antioxidants. The aim of this study was to investigate the effects of taurine treatment on nicotine-induced oxidative changes in rat urinary bladder and kidney and to explore the possible mechanisms of action. Male Wistar albino rats were injected with nicotine hydrogen bitartrate (0.6 mg/kg i.p.) or saline for 21 days. Taurine was administered (50 mg/kg i.p.) alone or along with nicotine injections. At the end of the treatment period bladder tissue was used for in vitro contractility studies, or stored along with kidney tissue for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Tissue samples were also examined histologically. Serum samples were stored for the measurement of MDA, GSH, blood urea nitrogen, creatinine and lactate dehydrogenase activity. Chronic nicotine treatment decreased the contractile activity of the bladder strips to carbachol and increased lipid peroxidation, MPO levels and tissue collagen content of the bladder and kidney samples. Taurine supplementation to nicotine-treated animals reversed the contractile dysfunction of the bladder strips. It also preserved the renal functions, restored the endogenous GSH levels and decreased high lipid peroxidation and MPO activities in both urinary bladder and kidney tissues. These data suggest that taurine supplementation effectively counteracts the deleterious effect of chronic nicotine administration on bladder and kidney functions and attenuates oxidative damage possibly by its antioxidant effects.

Abstract: Objective: In diabetes, intracellular accumulation of sorbitol resulting from the high extracellular levels of glucose leads to depletion of intracellular compounds including taurine This is associated with the development of late diabetic complications such as cardiomyopathy The development of myocyte hypertrophy has been largely attributed to angiotensin II, whose growth properties are antagonized by taurine However, the interaction between taurine, angiotensin II type2 receptor (AT2) and cardiomyopathy related to angiotensin II is still unknown This study investigates the roles of taurine and AT2 in rats with streptozotocin (STZ)-induced diabetic cardiomyopathy

Abstract: Hypochlorous acid (HOCl) released by activated leukocytes has been implicated in the tissue damage that characterizes chronic inflammatory diseases. In this investigation, 14 indole derivatives, including metabolites such as melatonin, tryptophan and indole-3-acetic acid, were screened for their ability to inhibit the generation of this endogenous oxidant by stimulated leukocytes. The release of HOCl was measured by the production of taurine-chloramine when the leukocytes (2 x 10(6) cells/mL) were incubated at 37 degrees C in 10 mM phosphate-buffered saline, pH 7.4, for 30 min with 5 mM taurine and stimulated with 100 nM phorbol-12-myristate acetate. Irrespective of the group substituted in the indole ring, all the compounds tested including indole, 2-methylindole, 3-methylindole, 2,3-dimethylindole, 2,5-dimethylindole, 2-phenylindole, 5-methoxyindole, 6-methoxyindole, 5-methoxy-2-methylindole, melatonin, tryptophan, indole-3-acetic acid, 5-methoxy-2-methyl-3-indole-acetic acid, and indomethacin (10 microM) inhibited the chlorinating activity of myeloperoxidase (MPO) in the 23-72% range. The compounds 3-methylindole and indole-3-acetic acid were chosen as representative of indole derivatives in a dose-response study using purified MPO. The IC50 obtained were 0.10 +/- 0.03 and 5.0 +/- 1.0 microM (N = 13), respectively. These compounds did not affect the peroxidation activity of MPO or the production of superoxide anion by stimulated leukocytes. By following the spectral change of MPO during the enzyme turnover, the inhibition of HOCl production can be explained on the basis of the accumulation of the redox form compound-II (MPO-II), which is an inactive chlorinating species. These results show that indole derivatives are effective and selective inhibitors of MPO-chlorinating activity.

Abstract: A simple method for quantification of conjugated bile acids in human bile using (1)H NMR spectroscopy is presented. Bile acids in human bile are essentially conjugated with either glycine or taurine. The amide NH resonances from the conjugated bile acids are invariably devoid of interfering signals in (1)H NMR spectra. Under physiologic conditions of human bile (pH approximately 7.0 to 7.7), amide signal intensities are attenuated due to the chemical exchange and hence quantitative estimation is precluded. In the present study, the quantity of total glycine and taurine conjugated bile acids could be obtained accurately by suppressing the amide exchange by reducing the pH slightly lower than physiologic value (6.0 +/- 0.5). Further, the quantity of glycine conjugated bile acids can be calculated accurately by subtracting the quantity of taurine conjugated bile acids from the total conjugated bile acids as determined from the present method.

Abstract: Mice lacking the farnesoid X receptor (FXR) involved in the maintenance of hepatic bile acid levels are highly sensitive to cholic acid-induced liver toxicity. Serum aspartate aminotransferase (AST) activity was elevated 15.7-fold after feeding a 0.25% cholic acid diet, whereas only slight increases in serum AST (1.7- and 2.5-fold) were observed in wild-type mice fed 0.25 and 1% cholic acid diet, respectively. Bile salt export pump mRNA and protein levels were increased in wild-type mice fed 1% cholic acid diet (2.1- and 3.0-fold) but were decreased in FXR-null mice fed 0.25% cholic acid diet. The bile acid output rate was 2.0- and 3.7-fold higher after feeding of 0.25 and 1.0% cholic acid diet in wild-type mice, respectively. On the other hand, no significant increase in bile acid output rate was observed in FXR-null mice fed 0.25% cholic acid diet in contrast to a significant decrease observed in mice fed a 1.0% cholic acid diet in spite of the markedly higher levels of hepatic tauro-conjugated bile acids. Unconjugated cholic acid was not detected in the bile of wild-type mice fed a control diet, but it was readily detected in wild-type mice fed 1% cholic acid diet. The ratio of biliary unconjugated cholic acid to total cholic acid (unconjugated cholic acid and tauro-conjugated cholic acid) reached 30% under conditions of hepatic taurine depletion. These results suggest that the cholic acid-induced enhancement of canalicular bile acid output rates and excretion of unconjugated bile acids are involved in adaptive responses for prevention of cholic acid-induced toxicity.

Abstract: Background: Cushing’s syndrome is associated with an increased cardiovascular risk Although a series of cardiovascular risk factors have been identified, sulfur amino acids (SAAs), recently indicated as independent cardiovascular risk factors, have been poorly investigated in patients with Cushing’s syndrome Aim: The aim of this cross-sectional controlled study was to evaluate serum and urinary levels and urinary excretion rate (ER) of SAAs in patients with Cushing’s disease (CD) during the active disease and after long-term disease remission Subjects and Methods: Forty patients with CD (20 with active disease and 20 with cured disease for at least 5 yr) and 40 controls entered the study Serum and urinary concentrations and urinary ER of SAAs, namely methionine, cystine, homocysteine, and taurine, weremeasuredbymeansofcationicexchangeHPLCSerumfolicacid and vitamin B12 levels were also evaluated in patients and controls and correlated to SAA levels Results: CD patients with active disease had higher serum and urinary concentrations of cystine and homocysteine, and lower serum and higher urinary concentrations and ER of taurine than cured patients and controls Vitamin B12levels were significantly decreased in patients with active disease compared with cured patients and controls, whereas folic acid levels were slightly decreased in patients than in controls In patients with active CD, urinary cortisol concentrations were significantly and inversely correlated to serum taurine and directly correlated to taurine urinary ER, and fasting serum glucose levels were significantly correlated to taurine urinary ER At the multiple regression analysis, urinary cortisol concentrations were the best predictors of taurine ER Conclusions: CD is associated with hyperhomocysteinemia and hypotaurinemia Glucocorticoid excess, acting directly or indirectly, seems to be the most responsible for this imbalance in SAA levels The long-term disease remission is accompanied by normalization of SAA levels Hyperhomocysteinemia and hypotaurinemia might contribute to the increased cardiovascular risk of CD (J Clin Endocrinol Metab 90: 6616–6622, 2005)