Pterostilbene Prevents Early Diabetic Retinopathy Alterations in a Rabbit Experimental Model
Oxidative stress generated by diabetes plays a key role in the development of diabetic retinopathy (DR), a common diabetic complication. DR remains asymptomatic until it reaches advanced stages, which complicate its treatment. Although it is known that good metabolic control is essential for preventing DR, knowledge of the disease is incomplete and an effective treatment with no side effects is lacking. Pterostilbene (Pter), a natural stilbene with good antioxidant activity, has proved to beneficially affect different pathologies, including diabetes. Therefore, our study aimed to analyse the protective and/or therapeutic capacity of Pter against oxidant damage by characterising early retina…
Long-Term Aspartame Administration Leads to Fibrosis, Inflammasome Activation, and Gluconeogenesis Impairment in the Liver of Mice
Background: Aspartame is an artificial sweetener used in foods and beverages worldwide. However, it is linked to oxidative stress, inflammation, and liver damage through mechanisms that are not fully elucidated yet. This work aimed to investigate the effects of long-term administration of aspartame on the oxidative and inflammatory mechanisms associated with liver fibrosis progression in mice. Methods: Mice were divided into two groups with six animals each: control and aspartame. Aspartame (80 mg/kg, via oral) or vehicle was administrated for 12 weeks. Results: Aspartame caused liver damage and elevated serum transaminase levels. Aspartame also generated liver fibrosis, as evidenced by his…
Oral Monosodium Glutamate Administration Causes Early Onset of Alzheimer's Disease-Like Pathophysiology in APP/PS1 Mice.
Glutamate excitotoxicity has long been related to Alzheimer's disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG, while wildtype mice were essentially not affected. Aβ and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, we…
Impacto de la metodología Online vs Presencial en las prácticas de Ciencias de la Salud.
[EN] New pedagogical methodologies in the field of health sciences are a necessary and important tool for students in training. At the moment we are living an exceptional situation due to the "COVID" pandemic. This has forced us to implement new learning methodologies. In the present study we evaluated the acquisition of basic competences for the application of knowledge, communication and interpretation of relevant data to make judgements in practices in students of the health sciences degree who carried out theoretical lessons and online practices using new tools and methodologies in comparison with students who carried out lectures and practices prior to COVID. The participants in the st…
FisioCovid
[EN] In the study plans of the first years of the degrees in Health Sciences it is usual to include basic and general subjects that are not very motivating for students with a more specific academic profile. Specifically, in the Degree in Optics and Optometry at the University of Valencia we encountered this problem when teaching General Physiology, a subject included within the Human and Ocular Physiology subject in the first year. Based on this background, we have considered developing the “FisioCovid” project as a pedagogical tool due to its condition of general interest to the population. The objective of this teaching innovation project is is to take advantage of the media and scientif…
Protein-bound tyrosine oxidation, nitration and chlorination by-products assessed by ultraperformance liquid chromatography coupled to tandem mass spectrometry
Abstract Background Free radicals cause alterations in cellular protein structure and function. Oxidized, nitrated, and chlorinated modifications of aromatic amino acids including phenylalanine and tyrosine are reliable biomarkers of oxidative stress and inflammation in clinical conditions. Objective To develop, validate and apply a rapid method for the quantification of known hallmarks of tyrosine oxidation, nitration and chlorination in plasma and tissue proteins providing a snapshot of the oxidative stress and inflammatory status of the organism and of target organs respectively. Material and Methods The extraction and clean up procedure entailed protein precipitation, followed by protei…
PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism
Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is a transcriptional coactivator described as a master regulator of mitochondrial biogenesis and function, including oxidative phosphorylation and reactive oxygen species detoxification. PGC-1α is highly expressed in tissues with high energy demands, and it is clearly associated with the pathogenesis of metabolic syndrome and its principal complications including obesity, type 2 diabetes mellitus, cardiovascular disease, and hepatic steatosis. We herein review the molecular pathways regulated by PGC-1α, which connect oxidative stress and mitochondrial metabolism with inflammatory response and metabolic syndrome. PGC-1α regula…
Las clases prácticas de Fisiología Humana y el trabajo previo del estudiante utilizando la plataforma MOODLE: un estudio a pie de aula
[EN] Among the most novel transformations our educational model has undergone, we find the introduction of innovative teaching methodologies that seek to promote the autonomous work of the student. In the subject of Human Physiolgy, practical teaching is essential. However, students need an extensive theoretical review previous to the practical lesson that consume a significant part of the time allocated to practical learning. In this work, we have developed an innovative teaching methodology that encourages students of the Degree in Optics and Optometry of the University of Valencia to prepare practical lessons in advance by solving previous questionnaires in MOODLE. This enhances their ab…
Hypoxic preconditioning induces neuroprotection against oxidative stress
Brain is an oxyregulator organ, however extremely vulnerable to oxygen. Both high and low oxygen concentrations generate free radicals and may cause oxidative stress and damage because of an insufficient response of the antioxidant system. Hypoxic preconditioning (HP) exerts neuroprotective effects and may be a protecting tool against oxygen fluctuations, thus preventing neuronal damage in events such as ischaemia, acute hypoxia, stroke, or traumatic brain injury, among others. This review aims to discuss the molecular mechanisms involved in the neuroprotective action of HP against oxidative stress and subsequently upon the brain under pro-oxidant conditions. Activation of the antioxidant d…
Impairment of PGC-1 Alpha Up-Regulation Enhances Nitrosative Stress in the Liver during Acute Pancreatitis in Obese Mice
Acute pancreatitis is an inflammatory process of the pancreatic tissue that often leads to distant organ dysfunction. Although liver injury is uncommon in acute pancreatitis, obesity is a risk factor for the development of hepatic complications. The aim of this work was to evaluate the role of PGC-1&alpha
Target oxygen levels in preterm neonates
To achieve postnatal adaptation newly born infant need to aerate the lungs, reduce pulmonary vascular resistance, and initiate oxygen and carbon dioxide exchange. The cornerstone of newborn resuscitation resides therefore in the establishment of a functional residual capacity and an adequate oxygenation. Recent guidelines have established guidelines concerning oxygen supplementation in preterm infants in the delivery room (DR); however, they are vague and unspecific. Herewith, we will address available information regarding the use of oxygen supplementation in the DR in preterm infants to satisfactorily overcome postnatal adaptation. Introduction: Resuscitation of the newborn is considered …
Cerebral protection during fetal-to-neonatal transition under hypoxic atmosphere
Newborn asphyxia is a complication during the perinatal period. The use of O2 for resuscitation has been broadly used in clinic. However, it has been demonstrated that oxygen overexposure induces oxidative stress (OS). We speculate that delaying postnatal in the extrauterine oxygenation status would preserve reducing equivalents, enhance redox adaptation, and protect oxyregulator tissues. The objective is evaluated OE status, induced by Fetal-Neonatal Transition (FNT) under different FiO2 conditions, in brain. FiO2 in pregnant mice was reduced from 21% to 14% or not the night before of delivery (G19). 8 hours after birth both group were led to room air (Hx14/21 and Nx21/21 groups) or hypero…
Prolonging in utero-like oxygenation after birth diminishes oxidative stress in the lung and brain of mice pups☆
Background Fetal-to-neonatal transition is associated with oxidative stress. In preterm infants, immaturity of the antioxidant system favours supplemental oxygen-derived morbidity and mortality. Objectives To assess if prolonging in utero-like oxygenation during the fetal-to-neonatal transition limits oxidative stress in the lung and brain, improving postnatal adaptation of mice pups. Material and methods Inspiratory oxygen fraction (FiO2) in pregnant mice was reduced from 21% (room air) to 14% (hypoxia) 8–12 h prior to delivery and reset to 21% 6–8 h after birth. The control group was kept at 21% during the procedure. Reduced (GSH) and oxidized (GSSG) glutathione and its precursors [γ-glut…
7,8-hydroxy-2′-deoxyguanosine/2′-deoxiguanosine ratio determined in hydrolysates of brain DNA by ultrachromatrography coupled to tandem mass spectrometry
7,8-hydroxy-2'-deoxyguanosine (8-OHdG) is an abundant DNA lesion formed by oxidation of the nucleoside 2'-deoxyguanosine (2-dG) and one of the most studied and accepted oxidative stress biomarkers. 8-OHdG has a strong carcinogenic potential, and prolonged oxidative stress heightens pathological conditions and especially cancer risk. Our aim was to develop, validate and apply a reliable method to assess DNA oxidation in genomic cellular DNA of sensible target organs such as brain. A procedure to isolate and digest the DNA of brain tissue properly for further detection of 8-OHdG and 2-dG by Ultra Performance Liquid Chromatography tandem Mass Spectrometry (UPLC-MS/MS) was optimized. The UPLC-M…
Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine β-synthase
© 2019 Published by Elsevier B.V.
Impact of Donor Human Milk in the Preterm Very Low Birth Weight Gut Transcriptome Profile by Use of Exfoliated Intestinal Cells
[Background] Own mother’s milk (OMM) is the optimal nutrition for preterm infants. However, pasteurized donor human milk (DHM) is a valid alternative. We explored the differences of the transcriptome in exfoliated epithelial intestinal cells (EEIC) of preterm infants receiving full feed with OMM or DHM.
Analysis of Lipid Peroxidation by UPLC-MS/MS and Retinoprotective Effects of the Natural Polyphenol Pterostilbene
The loss of redox homeostasis induced by hyperglycemia is an early sign and key factor in the development of diabetic retinopathy. Due to the high level of long-chain polyunsaturated fatty acids, diabetic retina is highly susceptible to lipid peroxidation, source of pathophysiological alterations in diabetic retinopathy. Previous studies have shown that pterostilbene, a natural antioxidant polyphenol, is an effective therapy against diabetic retinopathy development, although its protective effects on lipid peroxidation are not well known. Plasma, urine and retinas from diabetic rabbits, control and diabetic rabbits treated daily with pterostilbene were analyzed. Lipid peroxidation was evalu…
Assessment of oxidative damage to proteins and DNA in urine of newborn infants by a validated UPLC-MS/MS approach
The assessment of oxidative stress is highly relevant in clinical Perinatology as it is associated to adverse outcomes in newborn infants. This study summarizes results from the validation of an Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of the urinary concentrations of a set of endogenous biomarkers, capable to provide a valid snapshot of the oxidative stress status applicable in human clinical trials, especially in the field of Perinatology. The set of analytes included are phenylalanine (Phe), para-tyrosine (p-Tyr), ortho-tyrosine (o-Tyr), meta-tyrosine (m-Tyr), 3-NO2-tyrosine (3NO(2)-Tyr), 3-Cl-tyrosine (3Cl-T…
Metabolomic Analysis of the Effect of Postnatal Hypoxia on the Retina in a Newly Born Piglet Model
The availability of reliable biomarkers of brain injury secondary to birth asphyxia could substantially improve clinical grading, therapeutic intervention strategies, and prognosis. In this study, changes in the metabolome of retinal tissue caused by profound hypoxia in an established neonatal piglet model were investigated using an ultra performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLC-QTOFMS) untargeted metabolomic approach, which included Partial Least Squares - Discriminant Analysis (PLSDA) multivariate data analysis. The initial identification of a set of discriminant metabolites from UPLC-QTOFMS data was confirmed by target UPLC-MS/MS and allowed t…