Taurine Abstracts 5

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Taurine mitigates cognitive impairment induced by chronic co-exposure of male Wistar rats to chlorpyrifos and lead acetate.
            (Akande et al., 2014) Download
Organophosphate pesticides and heavy metals are ubiquitous environmental pollutants and neurotoxicants. We investigated the effects of taurine (an antioxidant; TA) on oxidative stress and cognition in male Wistar rats co-treated with chlorpyrifos (an organophosphate pesticide; CPF) and lead acetate (heavy metal; LA). The Wistar rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil respectively. The remaining three groups were administered with taurine (TA), 50 mg/kg body weight, CPF+LA group [CPF (4.25 mg/kg, 1/20 LD₅₀] and LA (233.25 mg/kg, 1/20 LD₅₀) and TA+CPF+LA group [TA (50 mg/kg), CPF (4.25 mg/kg) and LA (233.25 mg/kg)]. The xenobiotics were administered once daily by oral gavage for 16 weeks. The results showed reductions in the activities of brain antioxidant enzymes and acetylcholinesterase, increased lipoperoxidation and histopathological alterations of the cerebral cortex in the CPF+LA group. However, TA mitigated perturbations in the activities of the antioxidant enzymes and acetylcholinesterase, counteracted oxidative stress and brain lipoperoxidation and attenuated neuronal degeneration induced by joint CPF and LA-induced neurotoxicity. The results suggested that TA is neuroprotective following chronic co-exposure of rats to CPF and LA.

The role of DNA repair in brain related disease pathology.
            (Canugovi et al., 2013) Download
Oxidative DNA damage is implicated in brain aging, neurodegeneration and neurological diseases. Damage can be created by normal cellular metabolism, which accumulates with age, or by acute cellular stress conditions which create bursts of oxidative damage. Brain cells have a particularly high basal level of metabolic activity and use distinct oxidative damage repair mechanisms to remove oxidative damage from DNA and dNTP pools. Accumulation of this damage in the background of a functional DNA repair response is associated with normal aging, but defective repair in brain cells can contribute to neurological dysfunction. Emerging research strongly associates three common neurodegenerative conditions, Alzheimer's, Parkinson's and stroke, with defects in the ability to repair chronic or acute oxidative damage in neurons. This review explores the current knowledge of the role of oxidative damage repair in preserving brain function and highlights the emerging models and methods being used to advance our knowledge of the pathology of neurodegenerative disease.

Neuroprotective role of taurine during aging.
            (El Idrissi et al., 2013) Download
Aging of the brain is characterized by several neurochemical modifications involving structural proteins, neurotransmitters, neuropeptides and related receptors. Alterations of neurochemical indices of synaptic function are indicators of age-related impairment of central functions, such as locomotion, memory and sensory performances. Several studies demonstrate that ionotropic GABA receptors, glutamate decarboxylase (GAD), and somatostatinergic subpopulations of GABAergic neurons are markedly decreased in experimental animal brains during aging. Additionally, levels of several neuropeptides co-expressed with GAD decrease during aging. Thus, the age-related decline in cognitive functions could be attributable, at least in part, to decrements in GABA inhibitory neurotransmission. In this study, we showed that chronic supplementation of taurine to aged mice significantly ameliorated the age-dependent decline in spatial memory acquisition and retention. We also demonstrated that concomitant with the amelioration in cognitive function, taurine caused significant alterations in the GABAergic and somatostatinergic system. These changes included (1) increased levels of the neurotransmitters GABA and glutamate, (2) increased expression of both isoforms of GAD (65 and 67) and the neuropeptide somatostatin, (3) decreased hippocampal expression of the β3 subunits of the GABAA receptor, (4) increased expression in the number of somatostatin-positive neurons, (5) increased amplitude and duration of population spikes recorded from CA1 in response to Schaefer collateral stimulation and (6) enhanced paired pulse facilitation in the hippocampus. These specific alterations of the inhibitory system caused by taurine treatment oppose those naturally occurring in the aging brain, suggesting a protective role of taurine in this process. An increased understanding of age-related neurochemical changes in the GABAergic system will be important in elucidating the underpinnings of the functional changes of aging. Taurine supplementation might help forestall the age-related decline in cognitive functions through interaction with the GABAergic system.

Taurine attenuates chemotherapy-induced nausea and vomiting in acute lymphoblastic leukemia.
            (Islambulchilar et al., 2015) Download
Taurine has multiple physiological activities and it is decreased by chemotherapy. The purpose of our study was to evaluate the effect of oral taurine supplementation on the incidence of chemotherapy-induced nausea and vomiting in patients with acute lymphoblastic leukemia. Forty young patients aged over 16 (range: 16-23 years) suffering from acute lymphoblastic leukemia (all receiving same chemotherapy regimen) were recruited for the study at the beginning of maintenance course of their chemotherapy. The study population was randomized in a double-blind manner to receive either taurine or placebo (2 g per day orally, divided into two doses, taken 6 h after chemotherapeutic agents) for 6 months. Life quality and adverse effects including nausea and vomiting, taste and smell alterations, and weariness were assessed using a questionnaire. Data were analyzed using Pearson's Chi-square test. Of 40 participants, 32 finished the study (14 female and 18 male; mean age 19.2 ± 1.9 years). Four treatment and four placebo arm patients discontinued: one immigrated from the province, one died during the study, and six refused to continue. The results indicated that taurine-supplemented patients reported a significant (P < 0.05) improvement in chemotherapy-induced nausea and/or vomiting after taking taurine during study. Taurine significantly improved chemotherapy-induced taste and smell alterations (P < 0.05). Moreover, taurine significantly reduced weariness compared to placebo group (P < 0.05). This study showed that taurine co-administration decreased chemotherapy-induced nausea and vomiting during the maintenance therapy in acute lymphoblastic leukemia.

Novel analgesic combination of tramadol, paracetamol, caffeine and taurine in the management of moderate to moderately severe acute low back pain.
            (Madhusudhan, 2013) Download
BACKGROUND:  Acute low back pain is one the leading cause of doctor's visit in our country with innumerable medication for treatment. Finding an ideal analgesic medication with better efficacy and least adverse effects is always a challenging task to the treating doctor. METHODS:  In this study we compared the efficacy and safety profile of a fixed dose combination of novel analgesic tramadol 37.5 mg/paracetamol 325 mg/caffeine 30 mg/taurine 250 mg with commonly used tramadol 37.5 mg/paracetamol 325 mg tablet in the treatment of moderate to moderately severe acute low back pain. Patients attending 50 clinics throughout India were enrolled in either of the above group and were asked to take one tablet every 6th hour for five consecutive days. The pain evaluation in both groups was done with verbal pain relief scale and pain intensity scale at end of treatment. RESULTS:  Proportion of patients in novel combination group compared to tramadol/paracetamol only group responding to treatment based on treatment satisfaction (good and excellent) and mean pain intensity (no pain or mild pain), were 81% Vs 45%, (p < 0.001) and 83% Vs 66% (p < 0.001) respectively. Common expected adverse drug reaction like nausea, vomiting and dizziness occurred with far less frequency in patients under novel combination group. CONCLUSION:  We conclude that significantly more patients in novel combination drug group compared to tramadol/paracetamol only group had a superior analgesic effect with lesser adverse reactions.


 

Taurine and central nervous system disorders.
            (Menzie et al., 2014) Download
In the present era, investigators seek to find therapeutic interventions that are multifaceted in their mode of action. Such targets provide the most advantageous routes for addressing the multiplicity of pathophysiological avenues that lead to neuronal dysfunction and death observed in neurological disorders and neurodegenerative diseases. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions in the central nervous system. In this review, we describe the mode of action of taurine and its clinical application in the neurological diseases: Alzheimer's disease, Parkinson's disease and Huntington's disease.

Does taurine prolong lifespan by improving heart function
            (Schaffer et al., 2015) Download
Taurine transporter knockout (TauTKO) mice die prematurely, an effect attributed to premature aging. However, taurine deficiency also causes severe pathology, including the development of a cardiomyopathy that can be fatal. The present review discusses one of the major mechanisms underlying the development of the cardiomyopathy. The cascade begins with taurine deficiency-mediated impairment of electron transport chain function, which mediates the initial decline in contractile function. The heart then begins the process of ventricular and biochemical remodeling, which worsens the severity of the contractile defect. A key defect that develops during ventricular remodeling is impaired sarcoplasmic reticular (SR) Ca2+ handling, which arises from a series of step that include elevated protein phosphatase 1 activity, diminished Ca2+-calmodulin-dependent protein kinase II (CaMKII) activity, reduced levels of phosphorylated phospho-lamban and finally impaired SR Ca2+ ATPase activity. Also contributing to ventricular remodeling is the loss of cardiomyocytes via apoptosis. Taurine deficiency also promotes premature aging, a complex phenomenon mediated in part by telomere shortening, elevations in mitochondrial ROS generation, mitochondrial DNA damage and inflammation. The initial insult driving premature aging in taurine deficient hearts is enhanced mitochondrial ROS generation, which in turn activates key signaling kinases that increase NF-κB content, leading to enhanced production of pro-inflammatory mediators. Chronic inflammation arises from both the production of pro-inflammatory mediators and the decline in taurine chloramine production, the latter which inhibits the inflammatory process. Finally, inflammation is a recognized mediator of premature aging


 

Taurine attenuates amyloid β 1-42-induced mitochondrial dysfunction by activating of SIRT1 in SK-N-SH cells.
            (Sun et al., 2014) Download
Amyloid β (Aβ) plays a critical role in the pathogenesis of Alzheimer disease (AD). Studies indicate that Aβ causes reactive oxygen species (ROS) generation, mitochondrial dysfunction and neurons loss in vivo and in vitro. Taurine, a naturally occurring β-amino acid in the brain, has been demonstrated to have neuroprotective properties. In the present study, the effects of taurine on cell viability and mitochondrial function in Aβ1-42-treated SK-N-SH cells were investigated. Pretreatment of taurine significantly attenuated Aβ1-42-induced neuronal death. Similarly, taurine suppressed the mPTP opening and reversed mitochondrial function in the presence of Aβ1-42. Additionally, taurine attenuated the intracellular Ca(2+) and ROS generation induced by Aβ1-42. Moreover, the expression of Sirtuin 1 (SIRT1) was obviously recovered by taurine in Aβ1-42-treated SK-N-SH cells. Our results suggest that taurine prevents Aβ1-42-induced mitochondrial dysfunction by activation of SIRT1. This study implies that taurine is a prospective additive for AD patients.

Taurine content in different brain structures during ageing: effect on hippocampal synaptic plasticity.
            (Suárez et al., 2016) Download
A reduction in taurine content accompanies the ageing process in many tissues. In fact, the decline of brain taurine levels has been associated with cognitive deficits whereas chronic administration of taurine seems to ameliorate age-related deficits such as memory acquisition and retention. In the present study, using rats of three age groups (young, adult and aged) we determined whether the content of taurine and other amino acids (glutamate, serine, glutamine, glycine, alanine and GABA) was altered during ageing in different brain areas (cerebellum, cortex and hippocampus) as well non-brain tissues (heart, kidney, liver and plasma). Moreover, using hippocampal slices we tested whether ageing affects synaptic function and plasticity. These parameters were also determined in aged rats fed with either taurine-devoid or taurine-supplemented diets. With age, we found heterogeneous changes in amino acid content depending on the amino acid type and the tissue. In the case of taurine, its content was reduced in the cerebellum of adult and aged rats, but it remained unchanged in the hippocampus, cortex, heart and liver. The synaptic response amplitude decreased in aged rats, although the late phase of long-term synaptic potentiation (late-LTP), a taurine-dependent process, was not altered. Our study highlights the stability of taurine content in the hippocampus during ageing regardless of whether taurine was present in the diet, which is consistent with the lack of changes detected in late-LTP. These results indicate that the beneficial effects of taurine supplementation might be independent of the replenishment of taurine stores.


References

Akande, MG, et al. (2014), ‘Taurine mitigates cognitive impairment induced by chronic co-exposure of male Wistar rats to chlorpyrifos and lead acetate.’, Environ Toxicol Pharmacol, 37 (1), 315-25. PubMed: 24394474
Canugovi, C, et al. (2013), ‘The role of DNA repair in brain related disease pathology.’, DNA Repair (Amst), 12 (8), 578-87. PubMed: 23721970
El Idrissi, A, CH Shen, and WJ L’amoreaux (2013), ‘Neuroprotective role of taurine during aging.’, Amino Acids, 45 (4), 735-50. PubMed: 23963537
Islambulchilar, M, et al. (2015), ‘Taurine attenuates chemotherapy-induced nausea and vomiting in acute lymphoblastic leukemia.’, Amino Acids, 47 (1), 101-9. PubMed: 25323734
Madhusudhan, SK (2013), ‘Novel analgesic combination of tramadol, paracetamol, caffeine and taurine in the management of moderate to moderately severe acute low back pain.’, J Orthop, 10 (3), 144-48. PubMed: 24396231
Menzie, J, et al. (2014), ‘Taurine and central nervous system disorders.’, Amino Acids, 46 (1), 31-46. PubMed: 22903433
Schaffer, SW, et al. (2015), ‘Does taurine prolong lifespan by improving heart function’, Adv Exp Med Biol, 803 555-70. PubMed: 25833527
Suárez, LM, et al. (2016), ‘Taurine content in different brain structures during ageing: effect on hippocampal synaptic plasticity.’, Amino Acids, 48 (5), 1199-208. PubMed: 26803657
Sun, Q, et al. (2014), ‘Taurine attenuates amyloid β 1-42-induced mitochondrial dysfunction by activating of SIRT1 in SK-N-SH cells.’, Biochem Biophys Res Commun, 447 (3), 485-89. PubMed: 24735533