Taurine Analogues Research Articles

An in-silico approach to the potential modulatory effect of taurine on sclerostin (SOST) and its probable role during osteoporosis

The cysteine-knot containing negative regulator of the Wnt (Wingless-related integration site) signaling pathway, sclerostin (SOST) is an emerging therapeutic target for osteoporosis. Its inhibition is responsible for the promotion of osteoblastogenesis. In this study, taurine, an amino sulfonic acid was used to study its mechanism of action for the inhibition of the SOST protein. Molecular docking and dynamic studies were performed as a part of the study whereby, it was observed that taurine binds to a probable allosteric pocket which allows it to modulate the structure of the SOST protein affecting all of the loops – loops 1, loop 2, and loop 3 – as well as the cysteine residues forming the cysteine-knot. The study also identified a set of seven taurine analogues that have better pharmacological activity than their parent compound using screening techniques. The conclusions derived from the study support that taurine has a probable antagonistic effect on the SOST protein directly through the modulation of HNQS motif and loops 2 and 3 and indirectly through its influence on the cysteine residues - 134, 165 and 167 C. Based on the results, it can be assumed that the binding of taurine with SOST protein probably reduces its binding affinity to the LRP6 protein greatly, while also inhibiting the target protein from anchoring to LRP4. Furthermore, it was noted that probable additional binding with any small molecule inhibitor (SMI) at the active site (PNAIG motif), in the presence of an already allosterically bound taurine, of the SOST protein would result in a complete potential antagonism of the target protein. Additionally, the study also uncovers the possible role of the GKWWRPS motif in providing stability to the PNAIG motif for the purpose of binding with LRP6. Communicated by Ramaswamy H. Sarma

Regulation of CXCR4 Expression by Taurine in Macrophage-Like Cells.

Taurine (2-aminoethanesulfonic acid) is a free β-amino acid found at high concentrations in many mammalian tissues. Taurine plays a role in several essential biological processes, including anti-oxidation, anti-inflammation, and osmoregulation. However, its regulatory mechanisms, especially at the genetic and molecular levels, have not been elucidated. Here, we targeted immune-related genes and investigated the effects of taurine on immune-related gene expression in macrophage-like cells. J774.1 cell line was used, and the effect of taurine on mRNA expression of immune-related genes such as cytokines, their receptors, and toll-like receptors was examined. Among these, taurine significantly increased the mRNA levels of C-X-C chemokine receptor 2 (CXCR2), chemokine receptor. Furthermore, we found that the taurine-induced increase in CXCR4 mRNA levels was higher than that in CXCR2 mRNA levels. Taurine increased both mRNA and protein expression levels of CXCR4. Additionally, we examined the effects of taurine analogs, including hypotaurine, β-alanine, and γ-aminobutyric acid (GABA). While GABA increased the mRNA expression of CXCR4, hypotaurine slightly increased this expression, and β-alanine had no effect, although these taurine analogs are the substrates of taurine transporter. These findings demonstrate that taurine specifically affects CXCR4 mRNA expression in macrophage-like cells.

Antisurdant properties of the structural analogue of taurin

The article presents the results of the study of the otoprotective effect of the structural analog of taurine in the case of sensorineural hearing loss. The work was performed on guinea pigs using electrophysiological and cytochemical methods. It is proved that the structural analogue of taurine has an antisurdantant (otoprotective) property, which manifests itself in restoring the amplitude-time characteristics of the potential of the auditory nerve action and the microphone potential of the cochlea. (For citation: Khnychenko LK, Petrova NN, Ilyinskaya EV, Tanchuk AE. Antisurdant properties of the structural analogue of taurin. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):25-32. doi: 10.17816/RCF16225-32).

The taurine transporter substrate guanidinoethyl sulfonate mimics the action of taurine on long-term synaptic potentiation.

Taurine is especially abundant in rodent brain where it appears to be involved in osmoregulation and synaptic plasticity mechanisms. The demonstration of a physiological role for taurine has been hampered by the difficulty in modifying taurine levels in most tissues, including the brain. We used an experimental strategy to reduce taurine levels, involving treatment with guanidinoethyl sulfonate (GES), a structural analogue of taurine that, among other properties, acts as a competitive inhibitor of taurine transport. GES delivered in the drinking water of rats for 1month effectively reduced taurine levels in brain structures (hippocampus, cerebellum and cortex) and outside the brain (heart, muscle, kidney, liver and plasma) by between 50 and 80%, depending on the tissue. This partial taurine depletion did not affect either basal synaptic transmission or the late phase of long-term potentiation (late-LTP) in hippocampal slices. In vivo microdialysis studies in the hippocampus revealed that GES treatment reduced extracellular taurine levels and the magnitude of taurine released in response to the application of either N-methyl-D-aspartate (NMDA) or a hypoosmotic solution, without affecting release mechanisms. Finally, we demonstrated in hippocampal slices that a brief GES application can mimic taurine action on the conversion of a decremental LTP into a perdurable late-LTP, concluding that GES might replace taurine function in some mechanisms such as those implicated in synaptic plasticity.

SY39-4 * INFLUENCE OF SYSTEMIC INFLAMMATORY PROCESSES ON BRAIN IMMUNE SYSTEM

Alcohol-induced inflammation plays an important part in the induction of alcohol induced brain damage. Increased peripheral inflammation, with the production of pro-inflammatory cytokines, possibly as a result of bacterial interaction with alcohol, acetaldehyde toxicity, macrophage stimulation or other factors, may act as important chemical messengers, which are able to traverse the blood brain barrier, BBB, and affect central nervous system function. Indeed in adolescent binge drinkers, changes in the plasma ratios of pro-inflammatory to anti-inflammatory cytokines are eviden. Once these cytokines have crossed the BBB, they may interact with receptors on glial cells thus enhancing the production of pro-inflammatory mediators which may lead to cognitive dysfunction. Since glial cells play an important role in the removal of neurotransmitter at the synaptic cleft, their activation may adversely affect this process thereby further contributing to cognitive dysfunction and depression. In addition increased glutamate excitotoxicity, as a result of alcohol detoxification, may contribute to the pro-inflammatory milieu. Animal studies have shown that the suppression of such an inflammatory response in the brain induced by chronic alcohol abuse and binge drinking by the administration of taurine analogues is beneficial in reducing both the inflammation and excessive glutamate production.

Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs.

Taurine activates and modulates GABA receptors in vivo as well as those expressed in heterologous systems. This study aimed to determine whether the structural analogs of taurine: homotaurine and hypotaurine, have the ability to activate GABA-A receptors that include GABAρ subunits. The expression of GABA-A receptors containing GABAρ has been reported in the STC-1 cells and astrocytes. In both cell types, taurine, homo-, and hypotaurine gated with low efficiency a picrotoxin-sensitive GABA-A receptor. The known bimodal modulatory effect of taurine on GABAρ receptors was not observed; however, differences between the activation and deactivation rates were detected when they were perfused together with GABA. In silico docking simulations suggested that taurine, hypo-, and homotaurine do not form a cation-π interaction such as that generated by GABA in the agonist-binding site of GABAρ. This observation complements the electrophysiological data suggesting that taurine and its analogs act as partial agonists of GABA-A receptors. All the observations above suggest that the structural analogs of taurine are partial agonists of GABA-A receptors that occupy the agonist-binding site, but their structures do not allow the proper interaction with the receptor to fully gate its Cl(-) channel.

Warfarin untargeted metabolomics study identifies novel procoagulant ethanolamide plasma lipids

Warfarin untargeted metabolomics study identifies novel procoagulant ethanolamide plasma lipids

Pyruvate-Dependent Changes in Neutrophil Amino- and Alpha-Keto Acid Profiles or Immunity: Which Mechanisms Are Involved?

High current findings indicate that a substitution with pyruvate can lead to significant alterations or even improvement in neutrophil immunonutrition. However, it is still unknown which intra-cellular pathways might be involved here. Hence, in this study, we investigated whether preincu-bation with an inhibitor of ·NO-synthase (L-NAME), an ·NO donor (SNAP), an analogue of taurine (beta-alanine), an inhibitor of ornithine-decarboxylase (DFMO) as well as a glutamine-analogue (DON), is able to alter the intragranulocytic metabolic response to pyruvate, here for example studied for neutrophil intracellular amino- and α-keto acid concentrations or important neutrophil immune functions [released myeloperoxidase (MPO), the formation of superoxide anions O2- and hydrogen peroxide (H2O2)]. In summary, the interesting first results presented here showed, that any damage of specific metabolic pathways or mechanisms, which seem directly or indirectly to be involved in relevant pyruvate dependent granulocytic nutrient content or specific cellular tasks, could lead to therapeutically desired, but also to unexpected or even fatal consequences for the affected cells. We therefore continue to believe that pyruvate, irrespective of which exact biochemical mechanisms were involved, in neutrophils may satisfy the substantial metabolic demands for a potent intracellular nutrient.

Warfarin Untargeted Metabolomics Study Identifies Novel Procoagulant Ethanolamide Lipids

Abstract 1200Untargeted metabolomics denotes the profiling of several thousand low molecular weight biochemicals, including lipids, hormones, saccharides, nucleotides, organic acids, and amino acids. The analytes are measured using mass spectrometry (MS) as molecule mass peaks without specific “targeting” of specific metabolites or analytes. We undertook an untargeted metabolomics investigation to define the effect of warfarin on plasma metabolite profiles in a crossover study of 17 venous thrombosis patients (9 male, 8 female) (age 58.1 ± 18.6 yr old; range 27–83 yr old). Blood was drawn at 4–6 weeks after initiation of warfarin (patients with an average INR 2.50 ± 0.65) and again at ∼ 10 days after discontinuation of the clinically determined course of warfarin. Plasmas were methanol-extracted and applied to a capillary reverse phase HPLC column, interfaced to an ESI-TOF mass spectrometer. Data were converted and aligned in the time domain using the program XCMS, with 3500–4500 distinct MS features found. Statistically significant differences were ranked using a paired t-test. In addition to warfarin metabolites, other changes were discovered. Several unique lipid metabolites, lyso-phosphatidylcholines (lyso-PC) (16:0 and 18:2), palmitoyl-ethanolamide (N-palmitoylethanolamine)(PEA) and stearoyl-ethanolamide (N-palmitoylethanolamine)(SEA), were identified as significantly decreased during warfarin therapy (p < 0.03)(See Table). PEA and SEA are naturally occurring saturated N-acylethanolamines (ethanolamides), both of which are structurally related to arachidonoyl (20:4) ethanolamide which binds to the cannabinoid receptor. PEA and SEA are devoid of affinity for cannabinoid receptors and physiological roles for PEA and SEA are unknown. When tested for effects on coagulation, exogenously added PEA (16:0) dose-dependently enhanced thrombin generation in plasma induced by tissue factor or calcium ions. SEA (18:0) and other lipid ethanolamides, e.g., arachidonoyl ethanolamide (20:4), also enhanced recalcification-induced thrombin generation in plasma. However, two analogs of PEA, palmitoyl N-isopropylamide and N-palmitoyl taurine which are lacking hydroxyl molecule in the head group, showed little enhancement of thrombin generation in plasma. These results suggest that the free hydroxyl group in the head group appears to be a key component for the observed procoagulant activity in ethanolamide family. How is it that warfarin might affect the metabolism of these lipids? The R-racemer of warfarin interacts with the pregnane X receptor (PNR) and increases CYP3A4 and CYP2C9 mRNAs levels in cultured human cells. Alternations in the catabolic activity of CYP3A4 might alter levels of ethanolamides and lyso-PC in patients. In summary, we employed the innovative untargeted metabolomics methods to identify endogenous biomarkers in warfarin-treated patients to help reveal biochemical changes triggered by this widely used drug which led to the discovery of a new family of plasma procoagulant molecules, namely ethanolamides. The downregulation of procoagulant ethanolamides by warfarin and its anticoagulant consequent effect might be minor, but may yet be an important additional anticoagulant property of warfarin. This study has implications for coagulation and plasma lipid relationships with potential clinical and pharmacologic applications.TablePlasma metabolites changed by warfarin treatmentNameMolecular formulaMH+ calculatedm/z observedFold changeP valuePEAC18H37NO2300.2897300.29082.8 ↓0.026SEAC20H41NO2328.3210328.31933.5 ↓0.030Lyso-PC(18:2)C26H50NO7P520.3397520.34243.5 ↓0.029Lyso-PC(16:0)C24H50NO7P496.3397496.33721.6 ↓0.006 Disclosures:No relevant conflicts of interest to declare.

Acamprosate modulates experimental autoimmune encephalomyelitis

This pilot study aimed to determine the efficacy of acamprosate (N-acetyl homotaurine) in reducing the pathological features of experimental autoimmune encephalomyelitis (EAE) which is an animal model for multiple sclerosis (MS). The amino acid taurine has multiple biological activities including immunomodulation and neuromodulation. The synthetic acetylated taurine derivative, acamprosate, which crosses the blood-brain barrier more readily compared to taurine, is currently being used for the prevention of alcohol withdrawal symptoms associated with enhanced glutamatergic receptor function and GABA receptor hypofunction. EAE was induced in C57BL/6 female mice with myelin oligodendrocyte glyocoprotein, amino acid 35-55. Mice were treated with 20, 100 and 500 mg/kg acamprosate for 21 days. Neurological scores at disease peak were reduced by 21, 64 and 9% in the 20, 100 and 500 mg/kg groups, respectively. Neurological improvement in the 100 mg/kg group correlated with a reduction in numbers of inflammatory lesions and the extent of CNS demyelination. Blood TNF-α levels were significantly reduced in the 500 mg/kg group. Acamprosate and other taurine analogs have a potential for future MS therapy.

S06 * ROLE OF INNATE IMMUNE SYSTEM IN THE ETHANOL-INDUCED BRAIN DAMAGE, BEHAVIOURAL DYSFUNCTIONS AND ADDICTION * S06.1 * BINGE DRINKING INDUCES SIGNIFICANT CHANGES IN THE INNATE IMMUNE SYSTEM

S06 * ROLE OF INNATE IMMUNE SYSTEM IN THE ETHANOL-INDUCED BRAIN DAMAGE, BEHAVIOURAL DYSFUNCTIONS AND ADDICTION * S06.1 * BINGE DRINKING INDUCES SIGNIFICANT CHANGES IN THE INNATE IMMUNE SYSTEM

Structural effects of N‐aromatic acyl‐amino acid conjugates on their deconjugation in the cecal contents of rats: implication in design of a colon‐specific prodrug with controlled conversion rate at the target site

N-aromatic acyl-amino acid conjugates possess a colon-targeted property, implying that such conjugates are stable and are not absorbable until reaching the large intestine in which they are microbially converted (hydrolysed) to the parent drugs that are therapeutically active. To investigate the structural effect of N-aromatic acyl-amino acid conjugates on the large intestinal deconjugation, the hydrolysis of various N-aromatic acyl-amino acid conjugates was examined in the cecal contents. On incubation of conjugates with glycine, D or/and L forms of alanine or phenylalanine in the cecal contents, the conjugates with D amino acids were not hydrolysed. The other conjugates are susceptible to the hydrolysis, the rates of which decreased as the size of the substituent on the 2-position of the amino acids increased. The conjugates with alkyl analogs (2-4 carbons) of glycine and taurine were resistant to the hydrolysis, while taurine- and glycine-conjugates were hydrolysed effectively. The hydrolysis of N-aromatic acyl-glycine conjugates was enhanced by para-substitution of electron withdrawing groups on the aromatic acyl moiety and vice versa for electron-donating groups. While a methyl, methoxy or chloro group on the ortho-position retarded the hydrolysis, a hydroxyl group on the position accelerated it. Our data may provide useful information for the design of a colon-specific prodrug with controlled conversion rate in the large intestine.

Taurine-like GABA aminotransferase inhibitors prevent rabbit brain slices against oxygen–glucose deprivation-induced damage

The activation of the GABAergic system has been shown to protect brain tissues against the damage that occurs after cerebral ischaemia. On the other hand, the taurine analogues (±)Piperidine-3-sulphonic- (PSA), 2-aminoethane phosphonic- (AEP), 2-(N-acetylamino) cyclohexane sulfonic-acids (ATAHS) and 2-aminobenzene sulfonate-acids (ANSA) have been reported to block GABA metabolism by inhibiting rabbit brain GABA aminotransferase and to increase GABA content in rabbit brain slices. The present investigation explored the neuroprotection provided by GABA, Vigabatrin (VIGA) and taurine analogues in the course of oxygen-glucose deprivation and reperfusion induced damage of rabbit brain slices. Tissue damage was assessed by measuring the release of glutamate and lactate dehydrogenase (LDH) during reperfusion and by determining final tissue water gain, measured as the index of cell swelling. GABA (30-300μM) and VIGA (30-300μM) significantly antagonised LDH and glutamate release, as well as tissue water gain caused by oxygen-glucose deprivation and reperfusion. Lower (1-10μM) or higher concentrations (up to 3,000μM) were ineffective. ANSA, PSA and ATAHS significantly reduced glutamate and LDH release and tissue water gain in a range of concentrations between 30 and 300μM. Lower (0-10μM) or higher (up to 3,000μM) concentrations were ineffective. Both mechanisms suggest hormetic ("U-shaped") effects. These results indicate that the GABAergic system activation performed directly by GABA or indirectly through GABA aminotransferase inhibition is a promising approach for protecting the brain against ischemia and reperfusion-induced damage.

Anti-inflammatory actions of a taurine analogue, ethane β-sultam, in phagocytic cells, in vivo and in vitro

The ability of a taurine prodrug, ethane β-sultam, to reduce cellular inflammation has been investigated, in vitro, in primary cultures of alveolar macrophages and an immortilised N9 microglial cell line and in vivo in an animal model of inflammation and control rats. Ethane β-sultam showed enhanced ability to reduce the inflammatory response in alveolar macrophages, as assayed by the lipopolysaccharide-stimulated–nitric oxide release, (LPS stimulated-NO), in comparison to taurine both in vitro (10nM, 50nM) and in vivo (0.15mmol/kg/day by gavage). In addition, ethane β-sultam, (50, 100 and 1000nM) significantly reduced LPS-stimulated glutamate release from N9 microglial cells to a greater extent than taurine. The anti-inflammatory response of taurine was shown to be mediated via stabilisation of IkBα. The use of a taurine prodrug as therapeutic agents, for the treatment of neurological conditions, such as Parkinson's and Alzheimer's disease and alcoholic brain damage, where activated phagocytic cells contribute to the pathogenesis, may be of great potential.

Determination of the natural abundance δ15 N of taurine by gas chromatography-isotope ratio measurement mass spectrometry

The measurement of the nitrogen isotope ratio of taurine (2-aminoethanesulphonic acid) in biological samples has a large number of potential applications. Taurine is a small water-soluble molecule which is notoriously difficult to analyze due to its polarity and functionality. A method is described which allows the determination of the natural abundance δ(15)N values of taurine and structural analogues, such as 3-amino-1-propanesulphonic acid (APSA), by isotope ratio mass spectrometry interfaced to gas chromatography (GC-irm-MS). The one-step protocol exploits the simultaneous derivatization of both functionalities of these aminosulphonic acids by reaction with triethylorthoacetate (TEOA). Conditions have been established which ensure quantitative reaction thus avoiding any nitrogen isotope fractionation during derivatization and workup. The differences in the δ(15)N values of derivatized and non-derivatized taurine and APSA all fall within the working range of 0.4‰ (-0.02 to 0.39‰). When applied to four sources of taurine with various δ(15)N values, the method achieved excellent reproducibility and accuracy. The optimized method enables the determination of the natural abundance δ(15)N values of taurine over the concentration range 1.5-7.84 µmol.mL(-1) in samples of biological origin.

Taurine, Bone Growth and Bone Development

Taurine (2-Amino ethane sulfonic acid) is a naturally occurring sulphur amino acid, found in several mammalian and non mammalian tissues. Taurine is believed to be involved in several life processes. Its deficiency is a cause of concern in developing abnormalities in many organs like eye, heart, kidney, brain etc during developmental stages and even later on. Taurine contents are believed to be high in bone tissue mostly due to accumulation by transport, as taurine synthesis in bone is yet to be recorded. A strong stimulating role of taurine in bone matrix formation and collagen synthesis has been observed in osteoblast like UMR-106 cells; together with this, inhibition of bone resorption and osteoclast formation by taurine has also been identified, making taurine an agent for preventing inflammatory bone resorption in periodontal diseases. Thus, taurine acts as a double beneficial agent; stimulating bone formation and inhibiting bone loss. Along with these actions in bone, it also has beneficial action in radio protection, wound healing, bone gain through exercise and many others. Taurine has the potential to replace bisphosphonates; suitable taurine analogues may further accelerate this. An extensive analytical study of taurine contents in both the stages of bone formation and bone loss may make taurine as a single marker of bone metabolism. However taurine-bone interaction needs more deep study towards regulation of taurine, interaction with ions, and many other pharmacological and physiological actions. An in depth clinical study of its actions in bone may make taurine an ideal agent for desired effect; yet, all these recorded taurine - bone interactions, are milestones for future research.

Taurine-Diabetes Interaction: From Involvement to Protection

Diabetes is a complex nature. To alleviate this, nutritional intervention provides much scope and hope, and taurine has been placed under this category successfully. An adult human weighing 70 kg contains about 70 g taurine. Taurine in diabetes has an age old story; taurine is involved in the development and protection of insulin apparatus. Taurine and insulin both have mutual stimulating actions with hypoglycemic properties. On the clinical front, taurine supplementation has acceptable beneficial effect in platelet aggregation and to name a few more, in neuropathy, cardiomyopathy, nephropathy and retinopathy. Recent studies have provided a role for taurine in fetal development and also in blocking the transfer of diabetes from diabetic mother to offspring. A number of mechanisms for taurine's actions have been advocated, from osmoregulation to anti-oxidation. Though sulfonylurea and recently introduced thiazolidinediones are effective, they are also not free from complications, thus needs to design new therapeutics. As taurine is also a sulfonyl derivative and it will be of great interest to develop taurine analogues as an alternative therapy. Considering the great involvement of taurine in diabetes, this review may provide a holistic view of taurine in diabetes and in its prevention, in this century.

Which mechanisms are involved in taurine-dependent granulocytic immune response or amino- and α-keto acid homeostasis?

We examined the effects of beta-alanine (taurine analogue and taurine transport antagonist), taurine (regarding its role in neutrophil (PMN) immunonutrition) and taurine combined either with L-NAME (inhibitor of *NO-synthase), SNAP (*NO donor), DON (glutamine-analogue and inhibitor of glutamine-requiring enzymes), DFMO (inhibitor of ornithine-decarboxylase) and beta-alanine on neutrophil amino- and alpha-keto acid profiles or important PMN immune functions in order to establish whether taurine transport-, nitric oxide-, glutamine- or ornithine-dependent mechanisms are involved in any of the taurine-induced effects. According to the present findings, the taurine-mediated effect appears to be based primarily on a modulation of important transmembraneous transport mechanisms and only secondarily on directly or indirectly induced modifications in intragranulocytic amino- and alpha-keto acid homoeostasis or metabolism. Although a direct relation to the parallel observed immunological modifications can only be presumed, these results show very clearly that compositional modifications in the free intragranulocytic amino- and alpha keto-acid pools coinciding with changes in intragranulocytic taurine levels are relevant metabolic determinants that can significantly influence the magnitude and quality of the granulocytic immune response.

The Effect of Mesna on Plasma Total Homocysteine Concentration in Hemodialysis Patients

Plasma total homocysteine (tHcy) level is an independent risk factor for the development of atherosclerosis. The degree of risk in most of the population is decreased by using dietary vitamin supplementation; however, more than 90% of patients with end-stage renal disease have increased tHcy levels despite supplementation. Only a small fraction of tHcy is removed by hemodialysis because of extensive disulfide bonding to albumin. The objective of this study is to determine whether a single intravenous dose of mesna, a thiol-containing drug analogue of taurine, facilitates tHcy clearance during hemodialysis. Initial in vitro thiol exchange tests were performed with mesna in plasma from dialysis patients. Mesna, 300 micromol/L (49.2 mg/L), was incubated with plasma at 37 degrees C, and free homocysteine was measured at various times. In vivo, mesna activity was tested in 10 hemodialysis patients by administering 2.5 or 5.0 mg/kg of mesna intravenously at the beginning of a treatment cycle. Blood samples were drawn throughout dialysis, and plasma tHcy levels were compared with those obtained from a previous dialysis session in which mesna was not administered. In vitro, mesna liberated 36.5% +/- 2.5% of protein-bound homocysteine in 30 minutes. In vivo, a single 2.5-mg/kg dose of mesna was ineffective; however, at 5.0 mg/kg, it caused a 55.2% +/- 3.9% decrease in plasma tHcy levels postdialysis compared with a 34.2% +/- 5.3% decrease with dialysis alone (P < 0.001). Intravenous mesna causes a rapid decrease in plasma tHcy levels during hemodialysis.

Pathways involved in alanyl-glutamine-induced changes in neutrophil amino- and α-keto acid homeostasis or immunocompetence

We examined the effects of DON [glutamine-analogue and inhibitor of glutamine-requiring enzymes], alanyl-glutamine (regarding its role in neutrophil immunonutrition) and alanyl-glutamine combined with L-NAME, SNAP, DON, beta-alanine and DFMO on neutrophil amino and alpha-keto acid concentrations or important neutrophil immune functions in order to establish whether an inhibitor of *NO-synthase [L-NAME], an *NO donor [SNAP], an analogue of taurine and a taurine transport antagonist [beta-alanine], an inhibitor of ornithine-decarboxylase [DFMO] as well as DON could influence any of the alanyl-glutamine-induced effects. In summary, irrespective of which pharmacological, metabolism-inhibiting or receptor-mediated mechanisms were involved, our results showed that impairment of granulocytic glutamine uptake, modulation of intracellular glutamine metabolisation and/or de novo synthesis as well as a blockade of important glutamine-dependent metabolic processes may led to significant modifications of physiological and immunological functions of the affected cells.