Changes in SOD and NF-κB Levels in Substantia Nigra and the Intestine through Oxidative Stress Effects in a Wistar Rat Model of Ozone Pollution.

This work aimed to elucidate how O3 pollution causes a loss of regulation in the immune response in both the brain and the intestine. In this work, we studied the effect of exposing rats to low doses of O3 based on the association between the antioxidant response of superoxide dismutase (SOD) levels and the nuclear factor kappa light chains of activated B cells (NFκB) as markers of inflammation. Method: Seventy-two Wistar rats were used, divided into six groups that received the following treatments: Control and 7, 15, 30, 60, and 90 days of O3. After treatment, tissues were extracted and processed using Western blotting, biochemical, and immunohistochemical techniques. The results indicated an increase in 4-hydroxynonenal (4HNE) and Cu/Zn-SOD and a decrease in Mn-SOD, and SOD activity in the substantia nigra, jejunum, and colon decreased. Furthermore, the translocation of NFκB to the nucleus increased in the different organs studied. In conclusion, repeated exposure to O3 alters the regulation of the antioxidant and inflammatory response in the substantia nigra and the intestine. This indicates that these factors are critical in the loss of regulation in the inflammatory response; they respond to ozone pollution, which can occur in chronic degenerative diseases.

Accumulation of Alpha-Synuclein and Increase in the Inflammatory Response in the substantia nigra, Jejunum, and Colon in a Model of O3 Pollution in Rats.

This work aimed to study the effect of repeated exposure to low doses of ozone on alpha-synuclein and the inflammatory response in the substantia nigra, jejunum, and colon. Seventy-two male Wistar rats were divided into six groups. Each group received one of the following treatments: The control group was exposed to air. The ozone groups were exposed for 7, 15, 30, 60, and 90 days for 0.25 ppm for four hours daily. Afterward, they were anesthetized, and their tissues were extracted and processed using Western blotting, immunohistochemistry, and qPCR. The results indicated a significant increase in alpha-synuclein in the substantia nigra and jejunum from 7 to 60 days of exposure and an increase in NFκB from 7 to 90 days in the substantia nigra, while in the jejunum, a significant increase was observed at 7 and 15 days and a decrease at 60 and 90 days for the colon. Interleukin IL-17 showed an increase at 90 days in the substantia nigra in the jejunum and increases at 30 days and in the colon at 15 and 90 days. Exposure to ozone increases the presence of alpha-synuclein and induces the loss of regulation of the inflammatory response, which contributes significantly to degenerative processes.

Ozone Environmental Pollution: Relationship between the Intestine and Neurodegenerative Diseases.

Repeated exposure to environmental ozone causes a chronic state of oxidative stress. This state is present in chronic degenerative diseases and induces a loss of control of the inflammatory response. Redox system dysfunction and failures in control of inflammatory responses are involved in a vicious circle that maintains and increases the degenerative process. The intestine also responds to secondary reactive species formed by exposure to ozone doses, generating noxious stimuli that increase degenerative damage. This review aims to elucidate how environmental pollution, mainly by ozone, induces a state of chronic oxidative stress with the loss of regulation of the inflammatory response, both in the intestine and in the brain, where the functionality of both structures is altered and plays a determining role in some neurodegenerative and chronic degenerative diseases. For this purpose, we searched for information on sites such as the Cochrane Library Database, PubMed, Scopus, and Medscape. Reviewing the data published, we can conclude that environmental pollutants are a severe health problem. Ozone pollution has different pathways of action, both molecular and systemic, and participates in neurodegenerative diseases such as Parkinson's and Alzheimer's disease as well in bowel diseases as Inflammatory Bowel Disease, Crohn's Disease, and Irritable Bowel Syndrome.

Ozone Pollution, Oxidative Stress, Regulatory T Cells and Antioxidants.

Ozone pollution, is a serious health problem worldwide. Repeated exposure to low ozone doses causes a loss of regulation of the oxidation-reduction systems, and also induces a chronic state of oxidative stress. This fact is of special importance for the regulation of different systems including the immune system and the inflammatory response. In addition, the oxidation-reduction balance modulates the homeostasis of these and other complex systems such as metabolism, survival capacity, cell renewal, and brain repair, etc. Likewise, it has been widely demonstrated that in chronic degenerative diseases, an alteration in the oxide-reduction balance is present, and this alteration causes a chronic loss in the regulation of the immune response and the inflammatory process. This is because reactive oxygen species disrupt different signaling pathways. Such pathways are related to the role of regulatory T cells (Treg) in inflammation. This causes an increase in chronic deterioration in the degenerative disease over time. The objective of this review was to study the relationship between environmental ozone pollution, the chronic state of oxidative stress and its effect on Treg cells, which causes the loss of regulation in the inflammatory response as well as the role played by antioxidant systems in various pathologies.

Chronic exposure to ozone induces cardiac antioxidant response and overexpression of either mitochondrial fision protein DRP1 and hipertrophyc-related proteins.

Pollution is considered a risk factor for cardiovascular disease; however, the mechanisms to explain this relationship are not well understood; ozone is one of the most abundant and studied air contaminants. Our study aimed to evaluate the effect of chronic exposition of rats to controlled low doses of ozone on oxidative stress, apoptosis, mitochondrial dynamics, and cardiac hypertrophy. Male Wistar rats were daily exposed to low ozone doses during 7, 15, 30, and 60 days, 4 h/day. Hearts were dissected, and homogenates were prepared. Oxidative stress was evaluated by TBARS and protein nitrosylation in addition to Superoxide dismutase 1 (SOD1) and Catalase levels; the apoptosis related-proteins caspase 3, caspase 9, Bax, Bcl-2, and the mitochondrial dynamic-associated proteins Fis1, Drp1, OPA1, and Mfn1 were quantified by western blot among the cardiac hypertrophy indicator alpha-actin (cardiac actin). There were no changes in the oxidative stress markers, however SOD1 expression increases. Caspase 3 expression decreased, whereas caspase 9 increased without changes in Bax or Bcl-2. Mitochondrial fission may be favored according to the increased expression of Drp1 but not changes in fusion-related proteins OPA1 and Mfn1. Finally, the molecular marker for cardiac hypertrophy was overexpressed after 30 and 60 days of ozone exposition. The chronic exposition to ozone induces a deleterious effect on cardiac mitochondria. Antioxidant defenses also show changes in relation to exposure time, as well as an apparent pro-hypertrophic effect associated with altered mitochondrial dynamics.

Oxidative Stress Caused by Ozone Exposure Induces Changes in P2X7 Receptors, Neuroinflammation, and Neurodegeneration in the Rat Hippocampus.

Low-ozone doses cause alterations in the oxidation-reduction mechanisms due to the increase in reactive oxygen species, alter cell signaling, and produce deleterious metabolic responses for cells. Adenosine 5'triphosphate (ATP) can act as a mediator in intercellular communication between neurons and glial cells. When there is an increase in extracellular ATP, a modification is promoted in the regulation of inflammation, energy metabolism, by affecting the intracellular signaling pathways that participate in these processes. The objective of this work was to study changes in the P2X7 receptor, and their relationship with the inflammatory response and energy metabolism, in a model of progressive neurodegeneration in the hippocampus of rats chronically exposed to low-ozone doses. Therefore, 72 male rats were exposed to low-ozone doses for different periods of time. After exposure to ozone was finished, rats were processed for immunohistochemical techniques, western blot, quantitative polymerase chain reaction (qPCR), and histological techniques for periodic acid-Schiff staining. The results showed immunoreactivity changes in the amount of the P2X7 protein. There was an increase in phosphorylation for glycogen synthase kinase 3-ß (GSK3-ß) as treatment continued. There were also increases in 27 interleukin 1 beta (IL-1 ß) and interleukin 17 (IL-17) and a decrease in interleukin 10 (IL-10). Furthermore, neuronal glycogen was found at 30 and 60 days, and an increase in caspase 3. An increase in mRNA was also shown for the P2X7 gene at 60 days, and GSK3-ß at 90 days of exposure. In conclusion, these results suggest that repeated exposure to low-ozone doses, such as those that can occur during highly polluted days, causes a state of oxidative stress, leading to alterations in the P2X7 receptors, which promote changes in the activation of signaling pathways for inflammatory processes and cell death, converging at a progressive neurodegeneration process, as may be happening in Alzheimer's disease.

5-S-cysteinyl-dopamine, a neurotoxic endogenous metabolite of dopamine: Implications for Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and is characterized for being an idiopathic and multifactorial disease. Extensive research has been conducted to explain the origin of the disease, but it still remains elusive. It is well known that dopamine oxidation, through the endogenous formation of toxic metabolites, is a key process in the activation of a cascade of molecular events that leads to cellular death in the hallmark of PD. Thio-catecholamines, such as 5-S-cysteinyl-dopamine, 5-S-glutathionyl-dopamine and derived benzothiazines, are endogenous metabolites formed in the dopamine oxidative degradation pathway. Those metabolites have been shown to be highly toxic to neurons in the substantia nigra pars compacta, activating molecular mechanisms that ultimately lead to neuronal death. In this review we describe the origin, formation and the toxic effects of 5-S-cysteinyl-dopamine and its oxidative derivatives that cause death to dopaminergic neurons. Furthermore, we correlate the formation of those metabolites with the neurodegeneration progress in PD. In addition, we present the reported neuroprotective strategies of products that protect against the cellular damage of those thio-catecholamines. Finally, we discuss the advantages in the use of 5-S-cysteinyl-dopamine as a potential biomarker for PD.

Effect of Chronic Oxidative Stress on Neuroinflammatory Response Mediated by CD4+T Cells in Neurodegenerative Diseases.

In a state of oxidative stress, there is an increase of reactive species, which induce an altered intracellular signaling, leading to dysregulation of the inflammatory response. The inability of the antioxidant defense systems to modulate the proinflammatory response is key to the onset and progression of neurodegenerative diseases. The aim of this work is to review the effect of the state of oxidative stress on the loss of regulation of the inflammatory response on the microglia and astrocytes, the induction of different CD4+T cell populations in neuroinflammation, as well as its role in some neurodegenerative diseases. For this purpose, an intentional search of original articles, short communications, and reviews, was carried out in the following databases: PubMed, Scopus, and Google Scholar. The articles reviewed included the period from 1997 to 2017. With the evidence obtained, we conclude that the loss of redox balance induces alterations in the differentiation and number of CD4+T cell subpopulations, leading to an increase in Th1 and Th17 response. This contributes to the development of neuroinflammation as well as loss of the regulation of the inflammatory response in neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), and Multiple Sclerosis (MS). In contrast, regulatory T cells (Tregs) and Th2 modulate the inflammatory response of effect of T cells, microglia, and astrocytes. In this respect, it has been found that the mobilization of T cells with anti-inflammatory characteristics toward damaged regions of the CNS can provide neuroprotection and become a therapeutic strategy to control inflammatory processes in neurodegeneration.

Structural Changes of Amyloid Beta in Hippocampus of Rats Exposed to Ozone: A Raman Spectroscopy Study.

The aim of this work was to study the effect of oxidative stress on the structural changes of the secondary peptide structure of amyloid beta 1-42 (Aß 1-42), in the dentate gyrus of hippocampus of rats exposed to low doses of ozone. The animals were exposed to ozone-free air (control group) and 0.25 ppm ozone during 7, 15, 30, 60, and 90 days, respectively. The samples were studied by: (1) Raman spectroscopy to detect the global conformational changes in peptides with α-helix and ß-sheet secondary structure, following the deconvolution profile of the amide I band; and (2) immunohistochemistry against Aß 1-42. The results of the deconvolutions of the amide I band indicate that, ozone exposure causes a progressively decrease in the abundance percentage of α-helix secondary structure. Furthermore, the ß-sheet secondary structure increases its abundance percentage. After 60 days of ozone exposure, the ß-sheet band is identified in a similar wavenumber of the Aß 1-42 peptide standard. Immunohistochemistry assays show an increase of Aß 1-42 immunoreactivity, coinciding with the conformational changes observed in the Raman spectroscopy of Aß 1-42 at 60 and 90 days. In conclusion, oxidative stress produces changes in the folding process of amyloid beta peptide structure in the dentate gyrus, leading to its conformational change in a final ß-sheet structure. This is associated to an increase in Aß 1-42 expression, similar to the one that happens in the brain of Alzheimer's Disease (AD) patients.

The Effect of Chronic Ozone Exposure on the Activation of Endoplasmic Reticulum Stress and Apoptosis in Rat Hippocampus.

The chronic exposure to low doses of ozone, like in environmental pollution, leads to a state of oxidative stress, which has been proposed to contribute to neurodegenerative disorders, including Alzheimer's disease (AD). It induces an increase of calcium in the endoplasmic reticulum (ER), which produces ER stress. On the other hand, different studies show that, in diseases such as Alzheimer's, there exist disturbances in protein folding where ER plays an important role. The objective of this study was to evaluate the state of chronic oxidative stress on ER stress and its relationship with apoptotic death in the hippocampus of rats exposed to low doses of ozone. We used 108 male Wistar rats randomly divided into five groups. The groups received one of the following treatments: (1) Control (air); (2) Ozone (O3) 7 days; (3) O3 15 days; (4) O3 30 days; (5) O3 60 days; and (6) O3 90 days. Two hours after each treatment, the animals were sacrificed and the hippocampus was extracted. Afterwards, the tissue was processed for western blot and immunohistochemistry using the following antibodies: ATF6, 78 kDa glucose-regulated protein (GRP78) and caspase 12. It was also subjected to terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and electronic microscopy. Our results show an increase in ATF6, GRP78 and caspase 12 as well as ER ultrastructural alterations and an increase of TUNEL positive cells after 60 and 90 days of exposure to ozone. With the obtained results, we can conclude that oxidative stress induced by chronic exposure to low doses of ozone leads to ER stress. ER stress activates ATF6 inducing the increase of GRP78 in the cytoplasm, which leads to the increase in the nuclear translocation of ATF6. Finally, the translocation creates a vicious cycle that, together with the activation of the cascade for apoptotic cell death, contributes to the maintenance of ER stress. These events potentially contribute in the neurodegeneration processes in diseases like AD.

Obesity, Oxidative Stress, and Their Effect on Serum Heme Oxygenase-1 Concentrations and Insulin in Children Aged 3 to 5 Years in a Pediatric Hospital of the Ministry of Health CDMX.

BACKGROUND: Obesity during early stages of life may condition states of oxidative stress. Heme oxygenase-1 (HO-1) is an enzyme involved in oxidative metabolism; it has antioxidant and anti-inflammatory functions and is related in sensitivity to insulin. However, a high concentration of this enzyme has been described to cause alterations such as insulin resistance. The objective of this work was to study the relationship between obesity, oxidative stress, HO-1, and insulin in children aged 3 to 5 years. METHODS: To achieve our objective, we studied a control group of children (n = 50) and a group of obese children (n = 50) who underwent an anthropometric evaluation. Additionally, we quantified peroxidized lipids, oxidized low-density lipoproteins (Ox-LDLs), oxidized and reduced glutathione, HO-1, and insulin. We also calculated the homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-%B, and HOMA-%S indices. According to the data distribution, nonparametric and Spearman's rank correlation coefficient tests were conducted. RESULTS: The results demonstrate that obese children show a statistically relevant increase in BMI/age, serum concentrations of peroxidized lipids, Ox-LDLs, oxidized glutathione, HO-1, and insulin (p < 0.005). In addition, there was an increase in the HOMA-IR and HOMA-%B (p < 0.0001) indices and a decrease of reduced glutathione, as well as a reduction in the HOMA-%S, compared with the children of the control group (p < 0.003). CONCLUSIONS: With the results obtained, we can conclude that obese preschool children show a chronic state of oxidative stress, an increase of HO-1, and an incipient state of insulin resistance. Finally, the increased reactive oxygen species could be one of the leading factors involved in insulin resistance and Ox-LDL increase from the preschool stage.

Syntaxin 5 Overexpression and ß-Amyloid 1-42 Accumulation in Endoplasmic Reticulum of Hippocampal Cells in Rat Brain Induced by Ozone Exposure.

Oxidative stress is a risk factor for Alzheimer's disease and it is currently accepted that oxidative damage precedes the overproduction of A42 peptide. We have reported that ozone causes oxidative stress inducing neurodegeneration in the brain of rats. It is associated with A42 overproduction and intracellular accumulation in hippocampus. Organelles like mitochondria, intracellular membranes, and endoplasmic reticulum have been identified as sites of A42 production and accumulation affecting cellular metabolism. However whether ozone exposure induces overproduction and/or accumulation of A42 in endoplasmic reticulum has not been studied. We evaluated this effect in the endoplasmic reticulum of hippocampal cells of rats exposed chronically to low doses of ozone (0.25 ppm) at 7, 15, 30, 60, and 90 days. The effect of the presence of A42 in endoplasmic reticulum was analyzed evaluating the expression of the chaperone Syntaxin 5. Our results show an accumulation of A42 peptide in this organelle. It was observed by immunofluorescence and by WB in endoplasmic fractions from hippocampal cells of rats at 60 and 90 days of treatment. Significant overexpression of the chaperone Syntaxin 5 at 60 and 90 days of treatment was observed ((⁎) P < 0.05). These results indicate that the exposure to environmental pollutants could be involved as a risk factor for neurodegenerative processes.

CHANGES IN C-REACTIVE PROTEIN AND BIOCHEMICAL PROFILE IN PRESCHOOL CHILDREN WITH OBESITY.

INTRODUCTION: the childhood obesity is a serious public health problem because if weight gain continues, complications such as insulin resistance, dyslipidemia, orthopedic disorders, sleep apnea, and metabolic syndrome may occur in other stages of child development. OBJECTIVE: the objective of this study was to evaluate C-reactive protein (CRP) concentrations, lipid profiles, and glucose levels in obese children three to five years of age and compare them to eutrophic children. METHODS: in this study, 100 children aged three to five years were selected and divided into two groups (n = 50 per group): a group of eutrophic children (< 84th percentile) and a group of obese children (> 95th percentile). An anthropometric evaluation and quantification of plasma levels of ultrasensitive CRP, triglycerides, cholesterol, LDL-C, HDL-C, and glucose were performed. RESULTS: the data showed a significant increase in obese children with regard to height (p < 0.005), weight (p < 0.0001), body mass index (p < 0.0001), ultrasensitive CRP (p < 0.0001), triglycerides (p < 0.0001), LDL (p < 0.0001), and glucose levels (p < 0.0001) as well as decreased levels of HDL (p < 0.0001) compared to eutrophic children. CONCLUSIONS: metabolic changes that occur in obese preschool children are characterized by increases in inflammatory markers and lipid profiles. Considering that during preschool age the programming and number of adipocytes that will remain with the individual for the rest of their life are determined, this stage is crucial in the development of complications associated with obesity.

Introducción: la obesidad infantil es un grave problema de salud pública, ya que si el aumento de peso continúa, pueden producirse complicaciones tales como resistencia a la insulina, dislipidemia, trastornos ortopédicos, apnea del sueño y síndrome metabólico en otras etapas del desarrollo del niño. Objetivo: el objetivo de este trabajo fue estudiar las concentraciones de proteína C reactiva, perfil de lípidos y glucosa en niños de 3-5 años con obesidad, y compararlos con niños eutróficos. Métodos: para dicho fin, cien niños de 3 a 5 años de edad fueron seleccionados y divididos en dos grupos (n:50 por grupo); un grupo de niños eutróficos (percentil < 84) y un grupo de niños con obesidad (percentil > 95). Se realizó una evaluación antropométrica y una cuantificación en plasma de proteína C reactiva ultrasensible, triglicéridos, colesterol, LDL-C, HDL-C y glucosa. Resultados: los datos obtenidos muestran un aumento significativo en los niños que presentan obesidad en relación a la talla (p < 0,005), peso (p < 0,0001), índice de masa corporal (p < 0,0001), proteína C reactiva ultrasensible (p < 0,0001), triglicéridos (p < 0,0001), LDL (p < 0,0001) y glucosa (p < 0,0001), así como una disminución en los niveles de HDL (p < 0,0001), comparados con los niños eutróficos. Conclusiones: los cambios metabólicos presentes en los niños preescolares obesos son caracterizados por un incremento en los marcadores inflamatorios y del perfil de lípidos. Tomando en consideración que durante la edad preescolar se determinan la programación y el número de adipocitos que se tendrán en la vida del individuo, esta etapa es clave en el desarrollo de las complicaciones asociadas a la obesidad.

Oxidative Stress State Is Associated with Left Ventricular Mechanics Changes, Measured by Speckle Tracking in Essential Hypertensive Patients.

The oxidative stress state is characterized by an increase in oxygen reactive species that overwhelms the antioxidant defense; we do not know if these pathological changes are correlated with alterations in left ventricular mechanics. The aim was correlating the oxidative stress state with the left ventricular global longitudinal strain (GLS) and the left ventricular end diastolic pressure (LVEDP). Twenty-five patients with essential hypertension and 25 controls paired by age and gender were studied. All of the participants were subjected to echocardiography and biochemical determination of oxidative stress markers. The hypertensive patients, compared with control subjects, had significantly (p < 0.05) higher levels of oxidized proteins (5.03 ± 1.05 versus 4.06 ± 0.63 nmol/mg), lower levels of extracellular superoxide dismutase (EC-SOD) activity (0.045 ± 0.02 versus 0.082 ± 0.02 U/mg), higher LVEDP (16.2 ± 4.5 versus 11.3 ± 1.6 mm Hg), and lower GLS (-12% versus -16%). Both groups had preserved ejection fraction and the results showed a positive correlation of oxidized proteins with GLS (r = 0.386, p = 0.006) and LVEDP (r = 0.389, p = 0.005); we also found a negative correlation of EC-SOD activity with GLS (r = -0.404, p = 0.004) and LVEDP (r = -0.347, p = 0.014).

Changes in C-reactive protein and biochemical profile in preschool children with obesity / Cambios en la proteína C reactiva y perfil bioquímico en niños preescolares con obesidad

Introduction: the childhood obesity is a serious public health problem because if weight gain continues, complications such as insulin resistance, dyslipidemia, orthopedic disorders, sleep apnea, and metabolic syndrome may occur in other stages of child development. Objective: the objective of this study was to evaluate C-reactive protein (CRP) concentrations, lipid profiles, and glucose levels in obese children three to five years of age and compare them to eutrophic children. Methods: in this study, 100 children aged three to five years were selected and divided into two groups (n = 50 per group): a group of eutrophic children (< 84th percentile) and a group of obese children (> 95th percentile). An anthropometric evaluation and quantification of plasma levels of ultrasensitive CRP, triglycerides, cholesterol, LDL-C, HDL-C, and glucose were performed. Results: the data showed a significant increase in obese children with regard to height (p < 0.005), weight (p < 0.0001), body mass index (p < 0.0001), ultrasensitive CRP (p < 0.0001), triglycerides (p < 0.0001), LDL (p < 0.0001), and glucose levels (p < 0.0001) as well as decreased levels of HDL (p < 0.0001) compared to eutrophic children. Conclusions: metabolic changes that occur in obese preschool children are characterized by increases in inflammatory markers and lipid profiles. Considering that during preschool age the programming and number of adipocytes that will remain with the individual for the rest of their life are determined, this stage is crucial in the development of complications associated with obesity (AU)

Introducción: la obesidad infantil es un grave problema de salud pública, ya que si el aumento de peso continúa, pueden producirse complicaciones tales como resistencia a la insulina, dislipidemia, trastornos ortopédicos, apnea del sueño y síndrome metabólico en otras etapas del desarrollo del niño. Objetivo: el objetivo de este trabajo fue estudiar las concentraciones de proteína C reactiva, perfil de lípidos y glucosa en niños de 3-5 años con obesidad, y compararlos con niños eutróficos. Métodos: para dicho fin, cien niños de 3 a 5 años de edad fueron seleccionados y divididos en dos grupos (n:50 por grupo); un grupo de niños eutróficos (percentil 95). Se realizó una evaluación antropométrica y una cuantificación en plasma de proteína C reactiva ultrasensible, triglicéridos, colesterol, LDL-C, HDL-C y glucosa. Resultados: los datos obtenidos muestran un aumento significativo en los niños que presentan obesidad en relación a la talla (p < 0,005), peso (p < 0,0001), índice de masa corporal (p < 0,0001), proteína C reactiva ultrasensible (p < 0,0001), triglicéridos (p < 0,0001), LDL (p < 0,0001) y glucosa (p < 0,0001), así como una disminución en los niveles de HDL (p < 0,0001), comparados con los niños eutróficos. Conclusiones: los cambios metabólicos presentes en los niños preescolares obesos son caracterizados por un incremento en los marcadores inflamatorios y del perfil de lípidos. Tomando en consideración que durante la edad preescolar se determinan la programación y el número de adipocitos que se tendrán en la vida del individuo, esta etapa es clave en el desarrollo de las complicaciones asociadas a la obesidad (AU)

Oxidative stress-dependent changes in immune responses and cell death in the substantia nigra after ozone exposure in rat.

Parkinson's disease has been associated with the selective loss of neurons in the substantia nigra pars compacta. Increasing evidence suggests that oxidative stress plays a major role. The resulting increase in reactive oxygen species triggers a sequence of events that leads to cell damage, activation of microglia cells and neuroinflammatory responses. Our objective was to study whether chronic exposure to low doses of ozone, which produces oxidative stress itself, induces progressive cell death in conjunction with glial alterations in the substantia nigra. Animals were exposed to an ozone-free air stream (control) or to low doses of ozone for 7, 15, 30, 60, or 90 days. Each group underwent (1) spectrophotometric analysis for protein oxidation; (2) western blot testing for microglia reactivity and nuclear factor kappa B expression levels; and (3) immunohistochemistry for cytochrome c, GFAP, Iba-1, NFkB, and COX-2. Our results indicate that ozone induces an increase in protein oxidation levels, changes in activated astrocytes and microglia, and cell death. NFkB and cytochrome c showed an increase until 30 days of exposure, while cyclooxygenase 2 in the substantia nigra increased from 7 days up to 90 days of repetitive ozone exposure. These results suggest that oxidative stress caused by ozone exposure induces changes in inflammatory responses and progressive cell death in the substantia nigra in rats, which could also be occurring in Parkinson's disease.

Vitamin C in Health and Disease: Its Role in the Metabolism of Cells and Redox State in the Brain.

Ever since Linus Pauling published his studies, the effects of vitamin C have been surrounded by contradictory results. This may be because its effects depend on a number of factors such as the redox state of the body, the dose used, and also on the tissue metabolism. This review deals with vitamin C pharmacokinetics and its participation in neurophysiological processes, as well as its role in the maintenance of redox balance. The distribution and the concentration of vitamin C in the organs depend on the ascorbate requirements of each and on the tissue distribution of sodium-dependent vitamin C transporter 1 and 2 (SVCT1 and SVCT2). This determines the specific distribution pattern of vitamin C in the body. Vitamin C is involved in the physiology of the nervous system, including the support and the structure of the neurons, the processes of differentiation, maturation, and neuronal survival; the synthesis of catecholamine, and the modulation of neurotransmission. This antioxidant interacts with self-recycling mechanisms, including its participation in the endogenous antioxidant system. We conclude that the pharmacokinetic properties of ascorbate are related to the redox state and its functions and effects in tissues.

Deciphering an interplay of proteins associated with amyloid ß 1-42 peptide and molecular mechanisms of Alzheimer's disease.

Extracellular and intracellular accumulation of amyloid beta 1-42 peptide in different states of aggregation has been involved in the development and progression of Alzheimer's disease. However, the precise mechanisms involved in amyloid beta peptide neurotoxicity have not been fully understood. There exists a wide variety of studies demonstrating the binding of amyloid beta peptide to a great variety of macromolecules and that such associations affect the cellular functions. This type of association involves proteins and receptors anchored to the plasma membrane of neurons or immune cells of the central nervous system as well as intracellular proteins that can alter intracellular transport, activate signaling pathways or affect proper mitochondrial function. In this review, we present some examples of such associations and the role played by these interactions, which are generally involved in the pathological progression of Alzheimer's disease.

Oxidative stress activates the transcription factors FoxO 1a and FoxO 3a in the hippocampus of rats exposed to low doses of ozone.

The exposure to low doses of ozone induces an oxidative stress state, which is involved in neurodegenerative diseases. Forkhead box O (FoxO) family of transcription factors are activated by oxidative signals and regulate cell proliferation and resistance to oxidative stress. Our aim was to study the effect of chronic exposure to ozone on the activation of FoxO 1a and FoxO 3a in the hippocampus of rats. Male Wistar rats were divided into six groups and exposed to 0.25 ppm of ozone for 0, 7, 15, 30, 60, and 90 days. After treatment, the groups were processed for western blotting and immunohistochemistry against FoxO 3a, Mn SOD, cyclin D2, FoxO 1a, and active caspase 3. We found that exposure to ozone increased the activation of FoxO 3a at 30 and 60 days and expression of Mn SOD at all treatment times. Additionally, increases in cyclin D2 from 7 to 90 days; FoxO 1a at 15, 30, and 60 days; and activate caspase 3 from 30 to 60 days of exposure were noted. The results indicate that ozone alters regulatory pathways related to both the antioxidant system and the cell cycle, inducing neuronal reentry into the cell cycle and apoptotic death.