Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCl and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans

Whole-Blood Taurine Concentrations in Cats With Intestinal Disease

BackgroundIncreased delivery of taurine-conjugated bile acids to the distal bowel can lead to dysbiosis resulting in colitis in mouse models of inflammatory bowel disease. A similar situation also could occur in cats with intestinal disease and might therefore result in decreased whole-body taurine concentration.Hypothesis/objectivesTo determine whether whole-blood taurine concentrations are decreased at the time of diagnosis in cats with intestinal disease and to correlate concentrations with clinical and laboratory variables.AnimalsTwenty-one cats with chronic inflammatory enteropathy and 7 cats with intestinal neoplasia from the University of Bristol.MethodsCats that had undergone a thorough investigation consisting of a CBC, serum biochemistry, serum cobalamin and folate concentrations, transabdominal ultrasound examination and histopathology of intestinal biopsy specimens, as well as additional testing if indicated, were included. Whole-blood from these cats collected at the time of histologic diagnosis and stored in ethylenediaminetetraacetic acid was retrospectively analyzed for taurine with an automated high-performance liquid chromatography amino acid analyzer.ResultsAlthough whole-blood taurine concentrations remained within the reference range, those cats with predominantly large intestinal clinical signs had significantly lower concentrations than did cats with small intestinal and mixed bowel clinical signs (P = 0.033) and this difference also was significant when assessed only in cats with chronic inflammatory enteropathy (P = 0.019).Conclusions and clinical importanceAdditional studies are needed to determine whether large intestinal signs in cats with chronic inflammatory enteropathy are caused by alterations in the microbiota arising as a consequence of increased delivery of taurine-conjugated bile acids

Inhibitory postsynaptic actions of taurine, GABA and other amino acids on motoneurons of the isolated frog spinal cord

The actions of glycine, GABA, α-alanine, β-alanine and taurine were studied by intracellular recordings from lumbar motoneurons of the isolated spinal cord of the frog. All amino acids tested produced a reduction in the amplitude of postsynaptic potentials, a blockade of the antidromic action potential and an increase of membrane conductance. Furthermore, membrane polarizations occurred, which were always in the same direction as the IPSP. All these effects indicate a postsynaptic inhibitory action of these amino acids. When the relative strength of different amino acids was compared, taurine had the strongest inhibitory potency, followed by β-alanine, α α-alanine, GABA and glycine. Topically applied strychnine and picrotoxin induced different changes of postsynaptic potentials, indicating that distinct inhibitory systems might be influenced by these two convulsants. Interactions with amino acids showed that picrotoxin selectively diminished the postsynaptic actions of GABA, while strychnine reduced the effects of taurine, glycine, α- and β-alanine. But differences in the susceptibility of these amino acid actions to strychnine could be detected: the action of taurine was more sensitively blocked by strychnine compared with glycine, α- and β-alanine. With regard to these results the importance of taurine and GABA as transmitters of postsynaptic inhibition on motoneurons in the spinal cord of the frog is discussed

Potential protective role of reactive astrocytes in the periventricular parenchyma in congenital hydrocephalus

Background Cerebrospinal fluid accumulation in hydrocephalus produces an elevation of intraventricular pressure with pathological consequences on the periventricular brain parenchyma including ischemia, oedema, oxidative stress, and accumulation of metabolic waste products. Here we studied in the hyh mouse, an animal model of congenital hydrocephalus, the role of reactive astrocytes in this clinical degenerative condition. Materials and Methods Wild type and hydrocephalic hyh mice at 30 days of postnatal age were used. Three metabolites related to the oxidative and neurotoxic conditions were analysed in ex vivo samples (glutathione, glutamine and taurine) using High Resolution Magic Angle Spinning (HR-MAS). Glutathione synthetase and peroxidase, glutamine synthetase, kidney-type glutaminase (KGA), and taurine/taurine transporter were immunolocated in brain sections. Results Levels of the metabolites were remarkably higher in hydrocephalic conditions. Glutathione peroxidase and synthetase were both detected in the periventricular reactive astrocytes and neurons. Taurine was mostly found free in the periventricular parenchyma and in the reactive astrocytes, and the taurine transporter was mainly present in the neurons located in such regions. Glutamine synthetase was found in reactive astrocytes. Glutaminase was also detected in the reactive astrocytes and in periventricular neurons. These results suggest a possible protective response of reactive astrocytes against oxidative stress and neurotoxic conditions. Conclusions Astrocyte reaction seems to trigger an anti-oxidative and anti-neurotoxic response in order to ameliorate pathological damage in periventricular areas of the hydrocephalic mice.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. PI15-00619 to AJJ

Special topic: The association between pulse ingredients and canine dilated cardiomyopathy: addressing the knowledge gaps before establishing causation.

In July 2018, the Food and Drug Administration warned about a possible relationship between dilated cardiomyopathy (DCM) in dogs and the consumption of dog food formulated with potatoes and pulse ingredients. This issue may impede utilization of pulse ingredients in dog food or consideration of alternative proteins. Pulse ingredients have been used in the pet food industry for over 2 decades and represent a valuable source of protein to compliment animal-based ingredients. Moreover, individual ingredients used in commercial foods do not represent the final nutrient concentration of the complete diet. Thus, nutritionists formulating dog food must balance complementary ingredients to fulfill the animal's nutrient needs in the final diet. There are multiple factors that should be considered, including differences in nutrient digestibility and overall bioavailability, the fermentability and quantity of fiber, and interactions among food constituents that can increase the risk of DCM development. Taurine is a dispensable amino acid that has been linked to DCM in dogs. As such, adequate supply of taurine and/or precursors for taurine synthesis plays an important role in preventing DCM. However, requirements of amino acids in dogs are not well investigated and are presented in total dietary content basis which does not account for bioavailability or digestibility. Similarly, any nutrient (e.g., soluble and fermentable fiber) or physiological condition (e.g., size of the dog, sex, and age) that increases the requirement for taurine will also augment the possibility for DCM development. Dog food formulators should have a deep knowledge of processing methodologies and nutrient interactions beyond meeting the Association of American Feed Control Officials nutrient profiles and should not carelessly follow unsubstantiated market trends. Vegetable ingredients, including pulses, are nutritious and can be used in combination with complementary ingredients to meet the nutritional needs of the dog

Chronic cocaine enhances release of neuroprotective amino acid taurine: a microdialysis study

Cocaine inhibits high-affinity neurotransmitter uptake at the presynaptic nerve terminals to increase synaptic levels of dopamine, norepinephrine and serotonin^1^. This increase of synaptic dopamine may cause neurotoxicity^2,3^. At least two different mechanisms have been proposed for the development of dopamine-related neurotoxicity: 1) dopamine produces a free radical that may induce cell toxicity^2,3^ and 2) dopamine reduces glutamate transport at its presynaptic sites to increase synaptic levels of this amino acid^4^ and augments glutamate transmission by activating dopamine D1 receptors in different areas of the brain^5-7^. Increase in glutamatergic transmission mediated by the activation on N-methyl dextro-aspartate (NMDA) receptors has been shown to cause excitotoxicity and neuro-degeneration^8^. Others and we have reported protection against different psychotropic drug-induced neurotoxicity that may be achieved by prior or simultaneous administration of various pharmacological agents. For example, repeated treatment of rats with haloperidol induced neuronal damage that is ameliorated by prior administration of either GM1 ganglioside^9^ or the endogenous amino acid, taurine^10^. Similarly, chronic gestational cocaine exposure causes neurotoxicity that could be prevented by co-administration of clozapine^11^. To our knowledge, there is no information if chronic cocaine would enhance release of endogenous protective agents that may oppose the over activation of glutamatergic system. Here we show that repeated cocaine treatment increased synaptic levels of the neuroprotective amino acid taurine that opposes the excessive excitatory actions of the glutamatergic system in the rat brain. Thus, mammalian brain has an auto-protective mechanism to counter excitotoxicity and taurine or its synthetic derivative may be useful in the management and treatment of cocaine addiction and its neurotoxic effect

The Multifaceted Origin of Taurine Cattle Reflected by the Mitochondrial Genome

A Neolithic domestication of taurine cattle in the Fertile Crescent from local aurochsen (Bos primigenius) is generally accepted, but a genetic contribution from European aurochsen has been proposed. Here we performed a survey of a large number of taurine cattle mitochondrial DNA (mtDNA) control regions from numerous European breeds confirming the overall clustering within haplogroups (T1, T2 and T3) of Near Eastern ancestry, but also identifying eight mtDNAs (1.3%) that did not fit in haplogroup T. Sequencing of the entire mitochondrial genome showed that four mtDNAs formed a novel branch (haplogroup R) which, after the deep bifurcation that gave rise to the taurine and zebuine lineages, constitutes the earliest known split in the mtDNA phylogeny of B. primigenius. The remaining four mtDNAs were members of the recently discovered haplogroup Q. Phylogeographic data indicate that R mtDNAs were derived from female European aurochsen, possibly in the Italian Peninsula, and sporadically included in domestic herds. In contrast, the available data suggest that Q mtDNAs and T subclades were involved in the same Neolithic event of domestication in the Near East. Thus, the existence of novel (and rare) taurine haplogroups highlights a multifaceted genetic legacy from distinct B. primigenius populations. Taking into account that the maternally transmitted mtDNA tends to underestimate the extent of gene flow from European aurochsen, the detection of the R mtDNAs in autochthonous breeds, some of which are endangered, identifies an unexpected reservoir of genetic variation that should be carefully preserved

Interrogation of modern and ancient genomes reveals the complex domestic history of cattle

The analysis of mitochondrial and nuclear DNA sequence polymorphisms from modern cattle populations has had a profound impact on our understanding of the events surrounding the domestication of cattle. From these studies, it has been possible to distinguish between pre- and post-domestic genetic differentiation, supporting previous assertions from archaeological studies and, in some cases, revealing novel aspects of the demographic history of cattle. Analyses of genetic material retrieved from the remains of extinct ancestral wild cattle have also added valuable layers of information pertaining to cattle domestic origins; however, information from these investigations have, in general, been limited to small, variable portions of the mitochondrial genome owing to technical challenges associated with the retrieval and amplification of ancient DNA. In recent years, however, new high-throughput, massively parallel genomics technology platforms, such as single-nucleotide polymorphism (SNP) genotyping arrays and next-generation sequencing (NGS), have provided a new impetus to the studies of genetic variation in extant and ancient cattle. Arrays of SNP have facilitated high-resolution genetic surveys of global cattle populations and detection of ancient and recent genomic selective sweeps. Next-generation sequencing analyses of modern and ancient cattle hold great promise for identifying and cataloging of pre- and post-domestication patterns of genomic variation and correlating this with natural and artificial selection processes

Conformational variability of the glycine receptor M2 domain in response to activation by different agonists

Models describing the structural changes mediating cys-loop receptor activation generally give little attention to the possibility that different agonists may promote activation via distinct M2 pore-lining domain structural rearrangements. We investigated this question by comparing the effects of different ligands on the conformation of the external portion of the homomeric α1 glycine receptor M2 domain. Conformational flexibility was assessed by tethering a rhodamine fluorophore to cysteines introduced at the 19’ or 22’ positions and monitoring fluorescence and current changes during channel activation. During glycine activation, fluorescence of the label attached to R19’C increased by ~20% and the emission peak shifted to lower wavelengths, consistent with a more hydrophobic fluorophore environment. In contrast, ivermectin activated the receptors without producing a fluorescence change. Although taurine and β-alanine were weak partial agonists at the a1R19’C GlyR, they induced large fluorescence changes. Propofol, which drastically enhanced these currents, did not induce a glycine-like blue-shift in the spectral emission peak. The inhibitors, strychnine and picrotoxin, elicited fluorescence and current changes as expected for a competitive antagonist and an open channel blocker, respectively. Glycine and taurine (or β-alanine) also produced an increase and a decrease, respectively, in the fluorescence of a label attached to the nearby L22’C residue. Thus, results from two separate labelled residues support the conclusion that the GlyR M2 domain responds with distinct conformational changes to activation by different agonists

Ethane-beta-Sultam Modifies the Activation of the Innate Immune System Induced by Intermittent Ethanol Administration in Female Adolescent Rats

Intermittent ethanol abuse or ‘binge drinking’ during adolescence induces neuronal damage, which may be associated with cognitive dysfunction. To investigate the neurochemical processes involved, rats were administered either 1 g/kg or 2 g/kg ethanol in a ‘binge drinking’ regime. After only 3 weeks, significant activation of phagocytic cells in the peripheral (alveolar macrophages) and the hippocampal brain region (microglia cells) was present,as exemplified by increases in the release of pro-inflammatory cytokines in the macrophages and of iNOS in the microglia. This was associated with neuronal loss in the hippocampus CA1 region. Daily supplementation with a taurine prodrug, ethane-β-sultam, 0.028 g/kg, during the intermittent ethanol loading regime, supressed the release of the pro-inflammatory cytokines and of reactive nitrogen species, as well as neuronal loss, particularly in the rats administered the lower dose of ethanol, 1 g/kg. Plasma, macrophage and hippocampal taurine levels increased marginally after ethane-β-sultam supplementation. The ‘binge drinking’ ethanol rats administered 1 g/kg ethanol showed increased latencies to those of the control rats in their acquisition of spacial navigation in the Morris Water Maze, which was normalised to that of the controls values after ethane-β-sultam administration. Such results confirm that the administration of ethane-β-sultam to binge drinking rats reduces neuroinflammation in both the periphery and the brain, suppresses neuronal loss, and improved working memory of rats in a water maze study