RESUMEN
To realize the potential for the use of N-chlorotaurine (NCT) in healthcare, a better understanding of the long-term stability of the compound in water is needed. An array of analytical procedures is required that can measure changes in NCT concentration over time and allow for the detection and identification of contaminants and likely degradation end products. We used UV-Vis and NMR spectroscopy, HPLC, and LCMS to establish the stability of NCT in solutions subjected to prolonged ambient and elevated temperatures. Stability proved to be dependent on concentration with half-lives of ~120 days and ~236 days for 1% and 0.5% solutions of NCT at ~20 °C. Regardless of initial pH, all solutions shifted toward and maintained a pH of ~8.3 at 20 °C and 40 °C. NCT at 500 µg/mL and 250 µg /mL inhibited biofilm formation by Pseudomonas aeruginosa and Staphylococcus aureus but did not disperse established biofilms. NCT exposure to the biofilms had profound effects on the viability of both bacteria, reducing live organisms by >90%. Exposure of Interleukin-6 (IL-6) to 11 µM NCT reduced the binding of IL-6 to an immobilized specific antibody by ~48%, which is 5× the amount required for HOCl to bring about the same effect in this test system. Our data demonstrate the potency of the compound as an antimicrobial agent with potential benefits in the management of infected chronic wounds and suggest that NCT may contribute to anti-inflammatory processes in vivo by direct modification of cytokine mediators.
Asunto(s)
Biopelículas , Pseudomonas aeruginosa , Staphylococcus aureus , Taurina , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Taurina/farmacología , Taurina/química , Biopelículas/efectos de los fármacos , Estabilidad de Medicamentos , Interleucina-6/metabolismo , Concentración de Iones de Hidrógeno , Antibacterianos/farmacología , Antibacterianos/química , Soluciones , HumanosRESUMEN
N-chlorotaurine (NCT) is a broad-spectrum antimicrobial agent with outstanding tolerability, effective for topical and inhalation use. This paper presents the results of studies of single and repeated intravenous infusions of NCT to laboratory animals. The studies were conducted on female Wistar Han rats. The effect of NCT infusions on the general condition, behavioral reactions, main biochemical and hematological parameters, hemocoagulation system, cardiovascular system, and on the condition of the internal organs was studied. It was found that NCT infusions do not reveal deviations in the studied parameters that could indicate a toxic effect. The estimated LD50 is more than 80 mg/kg. In a subchronic experiment, a statistically significant decrease in cholesterol (by up to 11%), glucose (by up to 15%) and excess bases (up to four times) in the blood, and an increase in heart rate (by up to 31%) and frequency of defecations (by up to 35%), as well as pronounced antiplatelet effect, were found. In animals with simulated endotoxicosis, a decrease in the cytolysis and oxidative stress markers was observed. Such effects are caused by both chlorine-active compounds and taurine.The results obtained indicate broad prospects for the use of NCT solutions as an infusion detoxifying agent.
Asunto(s)
Ratas Wistar , Taurina , Animales , Taurina/análogos & derivados , Taurina/farmacología , Taurina/administración & dosificación , Femenino , Ratas , Estrés Oxidativo/efectos de los fármacos , Infusiones Intravenosas , Inactivación MetabólicaRESUMEN
Dental plaque bacteria play an important role in the pathogenicity of periodontitis and peri-implantitis. Therefore, antimicrobial agents are one means of treatment. N-chlorotaurine (NCT) as an endogenous well-tolerated topical antiseptic could be of advantage for this purpose. Accordingly, its microbicidal activity against some dental plaque bacteria was investigated at therapeutic concentrations in vitro. In quantitative killing assays, the activity of NCT against planktonic bacteria and against biofilms grown for 48 h on implantation screws was tested. Electron microscopy was used to demonstrate the formation of biofilm and its morphological changes. The killing of planktonic bacteria of all tested species, namely Streptococcus sanguinis, Streptococcus salivarius, Streptococcus oralis, Streptococcus cristatus, Rothia aeria, and Capnocytophaga ochracea, was shown within 10-20 min by 1% NCT in 0.01 M phosphate-buffered saline at 37 °C. Bacteria grown on screws for 24 h were inactivated by 1% NCT after 15-20 min as well, but the formation of biofilm on the screws was visible in electron microscopy not before 48 h. The killing of biofilms by 1% NCT was demonstrated after 30 min (streptococci) and 40 min (R. aeria). As expected, NCT has broad activity against dental plaque bacteria as well and should be further investigated on its clinical efficacy in periodontitis and peri-implantitis.
Asunto(s)
Biopelículas , Placa Dental , Taurina , Taurina/análogos & derivados , Taurina/farmacología , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Placa Dental/microbiología , Humanos , Periodontitis/microbiología , Periodontitis/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Streptococcus/efectos de los fármacosRESUMEN
Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in conditions like obesity, polycystic ovarian syndrome (PCOS), and diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced in a process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein glycation and AGEs formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress and acts as an anti-glycation compound, preventing in vitro glycation and AGEs accumulation. This study aimed to explore the ameliorative effects of a micronutrient support (Taurine, ALA and B6: TAB) on mouse oocytes challenged with MGO. Our results indicate that MGO reduces oocyte developmental competence, while TAB supplementation improves maturation, fertilization, and blastocyst formation rates. TAB also restores cell lineage allocation, redox balance and mitigates mitochondrial dysfunction in MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes in the transsulfuration pathway, and TAB enhances their mRNA expression. However, TAB does not rescue MGO-induced damage in denuded oocytes, emphasizing the supportive role of cumulus cells. Overall, these findings suggest that TAB interventions may have significant implications for addressing reproductive dysfunctions associated with elevated MGO/AGEs levels. This study highlights the potential of TAB supplementation in preserving the developmental competence of COCs exposed to MGO stress, providing insights into mitigating the impact of dicarbonyl stress on oocyte quality and reproductive outcomes.
Asunto(s)
Oocitos , Piruvaldehído , Taurina , Ácido Tióctico , Vitamina B 6 , Animales , Taurina/farmacología , Piruvaldehído/farmacología , Piruvaldehído/metabolismo , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Ratones , Ácido Tióctico/farmacología , Femenino , Vitamina B 6/farmacología , Vitamina B 6/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Estrés Oxidativo/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacosRESUMEN
Aging-related biochemical changes in nerve cells lead to dysfunctional synapses and disrupted neuronal circuits, ultimately affecting vital processes such as brain plasticity, learning, and memory. The imbalance between excitation and inhibition in synaptic function during aging contributes to cognitive impairment, emphasizing the importance of compensatory mechanisms. Fear conditioning-related plasticity of the somatosensory barrel cortex, relying on the proper functioning and extensive up regulation of the GABAergic system, in particular interneurons containing somatostatin, is compromised in aging (one-year-old) mice. The present research explores two potential interventions, taurine supplementation, and environmental enrichment, revealing their effectiveness in supporting learning-induced plasticity in the aging mouse brain. They do not act through a mechanism normalizing the Glutamate/GABA balance that is disrupted in aging. Still, they allow for increased somatostatin levels, an effect observed in young animals after learning. These findings highlight the potential of lifestyle interventions and diet supplementation to mitigate age-related cognitive decline by promoting experience-dependent plasticity.
Asunto(s)
Envejecimiento , Suplementos Dietéticos , Plasticidad Neuronal , Taurina , Animales , Plasticidad Neuronal/fisiología , Envejecimiento/fisiología , Taurina/metabolismo , Taurina/farmacología , Taurina/administración & dosificación , Ratones , Masculino , Somatostatina/metabolismo , Ratones Endogámicos C57BL , Aprendizaje/fisiología , Ambiente , Miedo/fisiología , Ácido gamma-Aminobutírico/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/prevención & control , Encéfalo/metabolismo , Encéfalo/fisiologíaRESUMEN
BACKGROUND: Cardiovascular disease (CVD) remains the foremost cause of mortality globally. Taurine, an amino acid, holds promise for cardiovascular health through mechanisms such as calcium regulation, blood pressure reduction, and antioxidant and anti-inflammatory effects. Despite these potential benefits, previous studies have yielded inconsistent results. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the existing evidence on the quantitative effects of taurine on hemodynamic parameters and cardiac function grading, which are indicative of overall cardiovascular health and performance. METHODS: We conducted an electronic search across multiple databases, including Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, from their inception to January 2, 2024. Our analysis focused on key cardiovascular outcomes, such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) Functional Classification. Meta-regression was applied to explore dose-dependent relationships based on the total taurine dose administered during the treatment period. A subgroup analysis, stratified according to the baseline disease status of patients, was also conducted. RESULTS: The analysis included a pooled sample of 808 participants from 20 randomized controlled trials. Taurine demonstrated a significant reduction in HR (weighted mean difference [WMD] = -3.579 bpm, 95% confidence interval [CI] = -6.044 to -1.114, p = 0.004), SBP (WMD = -3.999 mm Hg, 95% CI = -7.293 to -0.706, p = 0.017), DBP (WMD: -1.435 mm Hg, 95% CI: -2.484 to -0.386, p = 0.007), NYHA (WMD: -0.403, 95% CI: -0.522 to -0.283, p < 0.001), and a significant increase in LVEF (WMD: 4.981%, 95% CI: 1.556 to 8.407, p = 0.004). Meta-regression indicated a dose-dependent reduction in HR (coefficient = -0.0150 per g, p = 0.333), SBP (coefficient = -0.0239 per g, p = 0.113), DBP (coefficient = -0.0089 per g, p = 0.110), and NYHA (coefficient = -0.0016 per g, p = 0.111), and a positive correlation with LVEF (coefficient = 0.0285 per g, p = 0.308). No significant adverse effects were observed compared to controls. In subgroup analysis, taurine significantly improved HR in heart failure patients and healthy individuals. Taurine significantly reduced SBP in healthy individuals, heart failure patients, and those with other diseases, while significantly lowered DBP in hypertensive patients It notably increased LVEF in heart failure patients and improved NYHA functional class in both heart failure patients and those with other diseases. CONCLUSIONS: Taurine showed noteworthy effects in preventing hypertension and enhancing cardiac function. Individuals prone to CVDs may find it advantageous to include taurine in their daily regimen.
Asunto(s)
Presión Sanguínea , Enfermedades Cardiovasculares , Ensayos Clínicos Controlados Aleatorios como Asunto , Taurina , Taurina/farmacología , Taurina/administración & dosificación , Humanos , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Volumen Sistólico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Background: Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy. Moreover, current treatment regimens bear a significant risk of serious side effects. Thus, there is an unmet clinical need for effective therapies with improved safety profiles. Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines. Methods: In this study, we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma. K7M2 murine osteosarcoma cells were injected, both intramuscular and intraperitoneal, into 60 BALB/c mice on day zero. Animals were then randomized to receive treatment with taurolidine 2% (800 mg/kg), taurolidine 1% (400 mg/kg), or NaCl 0.9% control for seven days by intravenous or intraperitoneal administration. Results: After 35 days, mice were euthanized, and the tumors were harvested for analysis. Eighteen mice were excluded from the analysis due to complications. Body weight was significantly lower in the 2% taurolidine intraperitoneal treatment group from day 9 to 21, consistent with elevated mortality in this group. Intraperitoneal tumor weight was significantly lower in the 1% (p = 0.003) and 2% (p = 0.006) intraperitoneal taurolidine treatment groups compared to the control. No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine. There were no significant differences in microvessel density or mitotic rate between treatment groups. Reduced body weight and elevated mortality in the 2% taurolidine intraperitoneal group suggest that the lower 1% dose is preferable. Conclusions: In conclusion, there is no evidence of antiangiogenic activity, and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited. Moreover, its toxic profile grants further evaluation. Given these observations, further research is necessary to refine the use of taurolidine in osteosarcoma treatment.
Asunto(s)
Neoplasias Óseas , Modelos Animales de Enfermedad , Osteosarcoma , Taurina , Tiadiazinas , Carga Tumoral , Animales , Taurina/análogos & derivados , Taurina/farmacología , Taurina/uso terapéutico , Tiadiazinas/farmacología , Tiadiazinas/uso terapéutico , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Osteosarcoma/irrigación sanguínea , Ratones , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Carga Tumoral/efectos de los fármacos , Densidad Microvascular/efectos de los fármacos , Ratones Endogámicos BALB C , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Humanos , Neovascularización Patológica/tratamiento farmacológicoRESUMEN
Ferroptosis adversely affects the viability, differentiation, and metabolic integrity of C2C12 myoblasts, contributing to the decline in skeletal muscle health. The intricate mechanisms behind this process are not fully understood. In this study, we induced ferroptosis in myoblasts using targeted inducers and found a marked decrease in specific redox metabolites, particularly taurine. Taurine supplementation effectively reversed the deleterious effects of ferroptosis, significantly increased cellular glutathione levels, reduced MDA and ROS levels, and rejuvenated impaired myogenic differentiation. Furthermore, taurine downregulated HO-1 expression and decreased intracellular Fe2+ levels, thereby stabilizing the labile iron pool. Using NMR metabolomic analysis, we observed that taurine profoundly promoted glycerophospholipid metabolism, which is critical for cell membrane repair, and enhanced mitochondrial bioenergetics, thereby increasing the energy reserves essential for muscle satellite cell regeneration. These results suggest that taurine is a potent ferroptosis inhibitor that attenuates key drivers of this process, strengthens oxidative defenses, and improves redox homeostasis. This combined effect protects cells from ferroptosis-induced damage. This study highlights the potential of taurine as a valuable ferroptosis inhibitor that protects skeletal muscle from ferroptosis-induced damage and provides a basis for therapeutic strategies to rejuvenate and facilitate the regeneration of aging skeletal muscle.
Asunto(s)
Ferroptosis , Homeostasis , Hierro , Mioblastos , Oxidación-Reducción , Taurina , Taurina/farmacología , Ferroptosis/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Mioblastos/efectos de los fármacos , Mioblastos/metabolismo , Mioblastos/citología , Hierro/metabolismo , Animales , Ratones , Homeostasis/efectos de los fármacos , Línea Celular , Especies Reactivas de Oxígeno/metabolismo , Diferenciación Celular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Glutatión/metabolismo , Estrés Oxidativo/efectos de los fármacos , Glicerofosfolípidos/metabolismoRESUMEN
Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the DNA-damaging chemotherapeutic agent cisplatin. Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC. In culture, elevation of intracellular taurine concentration to OC ascites-cell-associated levels suppressed proliferation of various OC cell lines and patient-derived organoids, reduced glycolysis, and induced cell protection from cisplatin. Taurine cell protection was associated with decreased DNA damage in response to cisplatin. A combination of RNA sequencing, reverse-phase protein arrays, live-cell microscopy, flow cytometry, and biochemical validation experiments provided evidence for taurine-mediated induction of mutant or wild-type p53 binding to DNA, activation of p53 effectors involved in negative regulation of the cell cycle (p21), and glycolysis (TIGAR). Paradoxically, taurine's suppression of cell proliferation was associated with activation of pro-mitogenic signal transduction including ERK, mTOR, and increased mRNA expression of major DNA damage-sensing molecules such as DNAPK, ATM and ATR. While inhibition of ERK or p53 did not interfere with taurine's ability to protect cells from cisplatin, suppression of mTOR with Torin2, a clinically relevant inhibitor that also targets DNAPK and ATM/ATR, broke taurine's cell protection. Our studies implicate that elevation of intracellular taurine could suppress cell growth and metabolism, and activate cell protective mechanisms involving mTOR and DNA damage-sensing signal transduction.
Asunto(s)
Cisplatino , Daño del ADN , Neoplasias Ováricas , Serina-Treonina Quinasas TOR , Taurina , Proteína p53 Supresora de Tumor , Taurina/farmacología , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Femenino , Neoplasias Ováricas/metabolismo , Daño del ADN/efectos de los fármacos , Cisplatino/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Glucólisis/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Antineoplásicos/farmacologíaRESUMEN
The effects of intra-hippocampal manipulation of glycine receptors on the reconsolidation of recent and late long-term spatial memory were evaluated and assessed in the Morris water maze. The results obtained from the intra-hippocampal infusion of glycine and taurine demonstrated that taurine at a 100 nmol/side dose impaired the reconsolidation of recent and late long-term spatial memory. In comparison, at a dose of 10 nmol/side, it only affected the reconsolidation of late long-term spatial memory, reinforcing that there are differences between molecular mechanisms underlying recent and late long-term memory reconsolidation. On the other hand, glycine impaired the reconsolidation of early and late spatial memory when infused at a dose of 10 nmol/side, but not at a dose of 100 nmol/side, unless it is co-infused with an allosteric site antagonist of the NMDA receptor. Altogether these results show that glycine acting in situ in the hippocampal CA1 region exerts a pharmacological effect on U-curve, which can be explained by its concomitant action on its ionotropic receptor GlyR and on its NMDA receptor co-agonist site.
Asunto(s)
Glicina , Memoria a Largo Plazo , Ratas Wistar , Receptores de Glicina , Memoria Espacial , Taurina , Animales , Receptores de Glicina/metabolismo , Receptores de Glicina/efectos de los fármacos , Masculino , Glicina/farmacología , Ratas , Memoria Espacial/efectos de los fármacos , Memoria Espacial/fisiología , Memoria a Largo Plazo/efectos de los fármacos , Memoria a Largo Plazo/fisiología , Taurina/farmacología , Taurina/administración & dosificación , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Consolidación de la Memoria/efectos de los fármacos , Consolidación de la Memoria/fisiología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/fisiología , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiologíaRESUMEN
Taurine is a sulfur-containing amino acid found in many cell organelles that plays a wide range of biological roles, including bile salt production, osmoregulation, oxidative stress reduction, and neuromodulation. Taurine treatments have also been shown to ameliorate the onset and development of many diseases, including hypertension, fatty liver, neurodegenerative diseases and ischemia-reperfusion injury, by exerting antioxidant, anti-inflammatory, and antiapoptotic effects. The endoplasmic reticulum (ER) is a dynamic organelle involved in a wide range of cellular functions, including lipid metabolism, calcium storage and protein stabilization. Under stress, the disruption of the ER environment leads to the accumulation of misfolded proteins and a characteristic stress response called the unfolded protein response (UPR). The UPR protects cells from stress and helps to restore cellular homeostasis, but its activation promotes cell death under prolonged ER stress. Recent studies have shown that ER stress is closely related to the onset and development of many diseases. This article reviews the beneficial effects and related mechanisms of taurine by regulating the ER in different physiological and pathological states, with the aim of providing a reference for further research and clinical applications.
Asunto(s)
Estrés del Retículo Endoplásmico , Retículo Endoplásmico , Taurina , Taurina/metabolismo , Taurina/farmacología , Humanos , Animales , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrés del Retículo Endoplásmico/fisiología , Respuesta de Proteína Desplegada/efectos de los fármacos , Respuesta de Proteína Desplegada/fisiologíaRESUMEN
Effective treatment of patients with autism spectrum disorder (ASD) is still absent so far. Taurine exhibits therapeutic effects towards the autism-like behaviour in ASD model animals. Here, we determined the mechanism of taurine effect on hippocampal neurogenesis in genetically inbred BTBR T+ tf/J (BTBR) mice, a proposed model of ASD. In this ASD mouse model, we explored the effect of oral taurine supplementation on ASD-like behaviours in an open field test, elevated plus maze, marble burying test, self-grooming test, and three-chamber test. The mice were divided into four groups of normal controls (WT) and models (BTBR), who did or did not receive 6-week taurine supplementation in water (WT, WT+ Taurine, BTBR, and BTBR+Taurine). Neurogenesis-related effects were determined by Ki67 immunofluorescence staining. Western blot analysis was performed to detect the expression of phosphatase and tensin homologue deleted from chromosome 10 (PTEN)/mTOR/AKT pathway-associated proteins. Our results showed that taurine improved the autism-like behaviour, increased the proliferation of hippocampal cells, promoted PTEN expression, and reduced phosphorylation of mTOR and AKT in hippocampal tissue of the BTBR mice. In conclusion, taurine reduced the autism-like behaviour in partially inherited autism model mice, which may be associa-ted with improving the defective neural precursor cell proliferation and enhancing the PTEN-associated pathway in hippocampal tissue.
Asunto(s)
Trastorno Autístico , Hipocampo , Neurogénesis , Fosfohidrolasa PTEN , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Taurina , Animales , Taurina/farmacología , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Trastorno Autístico/metabolismo , Trastorno Autístico/tratamiento farmacológico , Masculino , Conducta Animal/efectos de los fármacos , Ratones , Modelos Animales de Enfermedad , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/tratamiento farmacológico , Proliferación Celular/efectos de los fármacosRESUMEN
Wound dressing diligently facilitate healing by fostering hemostasis, immunoregulation, the angiogenesis, and collagen deposition. Our methodology entails fabricating chitosan-taurine nanoparticles (CS-Tau) through an ionic gelation method. The morphology of CS-Tau was observed utilizing Transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Dynamic Light Scattering (DLS). The nanoparticles are subsequently incorporated into carboxymethyl chitosan hydrogels for crosslinking by EDC-NHS, yielding hydrogel dressings (CMCS-CS-Tau) designed to extend the duration of taurine release. In vitro investigations confirmed that these innovative compound dressings displayed superior biodegradation, biocompatibility, cytocompatibility, and non-toxicity, in addition to possessing anti-inflammatory properties, and stimulating the proliferation and mobility of human umbilical vein endothelial cells (HUVECs). Experiments conducted on mice models with full-thickness skin removal demonstrated that CMCS-CS-Tau efficaciously aided in wound healing by spurring angiogenesis, and encouraging collagen deposition. CMCS-CS-Tau can also minimize inflammation and promote collagen deposition in chronic diabetic wound. Hence, CMCS-CS-Tau promotes both acute and chronic diabetic wound healing. Furthermore, the sustained release mechanism of CMCS-CS-Tau on taurine reveals promising potential for extending its clinical utility in relation to various biological effects of taurine.
Asunto(s)
Quitosano , Células Endoteliales de la Vena Umbilical Humana , Hidrogeles , Nanopartículas , Taurina , Cicatrización de Heridas , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Nanopartículas/química , Humanos , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Taurina/análogos & derivados , Taurina/química , Taurina/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Masculino , Reactivos de Enlaces Cruzados/químicaRESUMEN
Taurine (2-aminoethanesulfonic acid) is a non-protein ß-amino acid essential for cellular homeostasis, with antioxidant, anti-inflammatory, and cytoprotective properties that are crucial for life maintenance. This study aimed to evaluate the effects of taurine administration on hippocampal neurogenesis, neuronal preservation, or reverse damage in rats exposed to forced ethanol consumption in an animal model. Wistar rats were treated with ethanol (EtOH) for a 28-day period (5% in the 1st week, 10% in the 2nd week, and 20% in the 3rd and 4th weeks). Two taurine treatment protocols (300 mg/kg i.p.) were implemented: one during ethanol consumption to analyze neuroprotection, and another after ethanol consumption to assess the reversal of ethanol-induced damage. Overall, the results demonstrated that taurine treatment was effective in protecting against deficits induced by ethanol consumption in the dentate gyrus. The EtOH+TAU group showed a significant increase in cell proliferation (145.8%) and cell survival (54.0%) compared to the EtOH+Sal group. The results also indicated similar effects regarding the reversal of ethanol-induced damage 28 days after the cessation of ethanol consumption. The EtOH+TAU group exhibited a significant increase (41.3%) in the number of DCX-immunoreactive cells compared to the EtOH+Sal group. However, this amino acid did not induce neurogenesis in the tissues of healthy rats, implying that its activity may be contingent upon post-injury stimuli.
Asunto(s)
Proteína Doblecortina , Etanol , Hipocampo , Neurogénesis , Fármacos Neuroprotectores , Ratas Wistar , Taurina , Animales , Taurina/farmacología , Neurogénesis/efectos de los fármacos , Masculino , Fármacos Neuroprotectores/farmacología , Ratas , Hipocampo/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Giro Dentado/efectos de los fármacos , Neuronas/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
Candida auris is an evolving and concerning global threat. Of particular concern are bloodstream infections related to central venous catheters. We evaluated the activity of taurolidine, a broad-spectrum antimicrobial in catheter lock solutions, against 106 C. auris isolates. Taurolidine was highly active with a MIC50/MIC90 of 512/512 mg/L, over 20-fold lower than lock solution concentrations of ≥13,500 mg/L. Our data demonstrate a theoretical basis for taurolidine-based lock solutions for prevention of C. auris catheter-associated infections.
Asunto(s)
Antifúngicos , Candida auris , Infecciones Relacionadas con Catéteres , Pruebas de Sensibilidad Microbiana , Taurina , Tiadiazinas , Tiadiazinas/farmacología , Taurina/análogos & derivados , Taurina/farmacología , Infecciones Relacionadas con Catéteres/microbiología , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Infecciones Relacionadas con Catéteres/prevención & control , Humanos , Antifúngicos/farmacología , Candida auris/efectos de los fármacos , Catéteres Venosos Centrales/microbiología , Catéteres Venosos Centrales/efectos adversos , Candidiasis/microbiología , Candidiasis/tratamiento farmacológico , Candidemia/microbiología , Candidemia/tratamiento farmacológicoRESUMEN
In brief: Mammalian spermatozoa actively generate reactive oxygen species (ROS) during capacitation, a maturational process necessary for fertilization in vivo. This study shows that hypotaurine, a precursor of taurine present in the oviduct, is incorporated and concentrated in hamster sperm cells via the taurine transporter, TauT, for cytoprotection against self-produced ROS. Abstract: To achieve fertilization competence, mammalian spermatozoa undergo capacitation, during which they actively generate reactive oxygen species (ROS). Therefore, mammalian spermatozoa must protect themselves from these self-generated ROS. The mammalian oviductal fluid is rich in hypotaurine, a taurine precursor, which reportedly protects mammalian spermatozoa, including those of hamsters, from ROS; however, its precise mechanism remains unknown. This study aimed to elucidate the mechanism underlying hypotaurine-mediated protection of spermatozoa from ROS using hamsters, particularly focusing on the taurine/hypotaurine transporter TauT. The effect of hypotaurine on sperm motility and ROS levels was tested using sperm motility analysis and the CellROX dye and luminol assays. RNA sequencing analysis was performed to verify TauT expression. We found that hypotaurine was necessary for maintaining sperm motility and hyperactivated motility. Hypotaurine did not scavenge extracellular ROS but lowered intracellular ROS levels and was incorporated and concentrated in hamster spermatozoa. TauT was detected at both mRNA and protein levels. ß-Alanine blocked hypotaurine transport, increased intracellular ROS levels, and inhibited hyperactivation. Elimination of Na+ or Cl- ions inhibited hypotaurine transport and increased intracellular ROS levels. Thus, these results indicated that hamster spermatozoa incorporated and concentrated hypotaurine in sperm cells via TauT to protect themselves from self-generated ROS.
Asunto(s)
Capacitación Espermática , Motilidad Espermática , Espermatozoides , Taurina , Animales , Cricetinae , Masculino , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Proteínas de Transporte de Membrana/genética , Mesocricetus , Especies Reactivas de Oxígeno/metabolismo , Capacitación Espermática/efectos de los fármacos , Motilidad Espermática/efectos de los fármacos , Espermatozoides/metabolismo , Espermatozoides/efectos de los fármacos , Taurina/análogos & derivados , Taurina/farmacologíaRESUMEN
The intricate process of neuronal differentiation integrates multiple signals to induce transcriptional, morphological, and electrophysiological changes that reshape the properties of neural precursor cells during their maturation and migration process. An increasing number of neurotransmitters and biomolecules have been identified as molecular signals that trigger and guide this process. In this sense, taurine, a sulfur-containing, non-essential amino acid widely expressed in the mammal brain, modulates the neuronal differentiation process. In this study, we describe the effect of taurine acting via the ionotropic GABAA receptor and the metabotropic GABAB receptor on the neuronal differentiation and electrophysiological properties of precursor cells derived from the subventricular zone of the mouse brain. Taurine stimulates the number of neurites and favors the dendritic complexity of the neural precursor cells, accompanied by changes in the somatic input resistance and the strength of inward and outward membranal currents. At the pharmacological level, the blockade of GABAA receptors inhibits these effects, whereas the stimulation of GABAB receptors has no positive effects on the taurine-mediated differentiation process. Strikingly, the blockade of the GABAB receptor with CGP533737 stimulates neurite outgrowth, dendritic complexity, and membranal current kinetics of neural precursor cells. The effects of taurine on the differentiation process involve Ca2+ mobilization and the activation of intracellular signaling cascades since chelation of intracellular calcium with BAPTA-AM, and inhibition of the CaMKII, ERK1/2, and Src kinase inhibits the neurite outgrowth of neural precursor cells of the subventricular zone.
Asunto(s)
Diferenciación Celular , Ventrículos Laterales , Células-Madre Neurales , Receptores de GABA-A , Receptores de GABA-B , Animales , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Células-Madre Neurales/efectos de los fármacos , Receptores de GABA-B/metabolismo , Ratones , Diferenciación Celular/efectos de los fármacos , Receptores de GABA-A/metabolismo , Ventrículos Laterales/citología , Ventrículos Laterales/metabolismo , Taurina/farmacología , Neurogénesis/efectos de los fármacos , Calcio/metabolismoRESUMEN
Taurine (Tau) is a semiessential amino acid in mammals with preventive and therapeutic effects on several intestinal disorders. However, the exact function of taurine in ulcerative colitis (UC) is still largely unclear. In this study, we used two taurine-deficient mouse models (CSAD-/- and TauT-/- mice) to explore the influence of taurine on the progression of UC in both dextran sulfate sodium (DSS)-induced colitis and LPS-stimulated Caco-2 cells. We found that cysteine sulfinic acid decarboxylase (CSAD) and taurine transporter (TauT) expressions and taurine levels were markedly reduced in colonic tissues of mice treated with DSS. The CSAD and TauT knockouts exacerbated DSS-induced clinical symptoms and pathological damage and aggravated the intestinal barrier dysfunction and the colonic mucosal inflammatory response. Conversely, taurine pretreatment enhanced the intestinal barrier functions by increasing goblet cells and upregulating tight junction protein expression. Importantly, taurine bound with TLR4 and inhibited the TLR4/NF-κB pathway, ultimately reducing proinflammatory factors (TNF-α and IL-6) and oxidative stress. Our findings highlight the essential role of taurine in maintaining the intestinal barrier integrity and inhibiting intestinal inflammation, indicating that taurine is a promising supplement for colitis treatment.
Asunto(s)
Colitis , Mucosa Intestinal , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B , Transducción de Señal , Taurina , Receptor Toll-Like 4 , Animales , Taurina/farmacología , Taurina/administración & dosificación , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Ratones , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colitis/inducido químicamente , Colitis/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Células CACO-2 , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Sulfato de Dextran/efectos adversos , Carboxiliasas/genética , Carboxiliasas/metabolismo , Funcion de la Barrera IntestinalRESUMEN
Taurine is considered a conditionally essential amino acid for fish, so its supplementation may improve feed conversion. This study evaluated the supplementation of taurine on growth performance, hematological and immunological parameters, production costs, and survival of Nile tilapia (Oreochromis niloticus) juveniles raised in a recirculating aquaculture system (RAS). A control diet was formulated with 360 g kg-1 of crude protein without fish meal and without taurine supplementation (Control). From the control diet, another diet supplemented with 9.7 g of taurine per kg of feed (Taurine) was produced. Fish fed diet supplemented with taurine had lower daily average weight gain and final average weight compared to the control diet (p < 0.05). It was observed that taurine had no influence on condition factor, survival, or hemato-immunological parameters of Nile tilapia juveniles, but there was a higher mean corpuscular volume and greater nitrogen retention in fish from the control group (p < 0.05). It is concluded that Nile tilapia juveniles do not benefit from taurine supplementation in RAS, even when fed diet containing plant-based protein sources.
Asunto(s)
Alimentación Animal , Acuicultura , Cíclidos , Suplementos Dietéticos , Taurina , Animales , Taurina/farmacología , Taurina/administración & dosificación , Acuicultura/métodos , Cíclidos/crecimiento & desarrolloRESUMEN
Ischemic stroke, a cerebrovascular disease caused by arterial occlusion in the brain, can lead to brain impairment and even death. Stem cell therapies have shown positive advantages to treat ischemic stroke because of their extended time window, but the cell viability is poor when transplanted into the brain directly. Therefore, a new hydrogel GelMA-T was developed by introducing taurine on GelMA to transplant neural stem cells. The GelMA-T displayed the desired photocuring ability, micropore structure, and cytocompatibility. Its compressive modulus was more similar to neural tissue compared to that of GelMA. The GelMA-T could protect SH-SY5Y cells from injury induced by OGD/R. Furthermore, the NE-4C cells showed better proliferation performance in GelMA-T than that in GelMA during both 2D and 3D cultures. All results demonstrate that GelMA-T possesses a neuroprotective effect for ischemia/reperfusion injury against ischemic stroke and plays a positive role in promoting NSC proliferation. The novel hydrogel is anticipated to function as cell vehicles for the transplantation of neural stem cells into the stroke cavity, aiming to treat ischemic stroke.