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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.
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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.
Asunto(s)
Colon , Yeyuno , Ozono , Sustancia Negra , alfa-Sinucleína , Animales , Masculino , Ratas , alfa-Sinucleína/metabolismo , Colon/metabolismo , Colon/efectos de los fármacos , Colon/patología , Inflamación/metabolismo , Inflamación/inducido químicamente , Inflamación/patología , Interleucina-17/metabolismo , Yeyuno/metabolismo , Yeyuno/efectos de los fármacos , Yeyuno/patología , FN-kappa B/metabolismo , Ozono/toxicidad , Ratas Wistar , Sustancia Negra/metabolismo , Sustancia Negra/efectos de los fármacos , Sustancia Negra/patologíaRESUMEN
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.
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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.
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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.
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Hipocampo/patología , Enfermedades Neurodegenerativas/patología , Enfermedades Neuroinflamatorias/patología , Neuronas/patología , Ozono/toxicidad , Receptores Purinérgicos P2X7/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Masculino , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neuroinflamatorias/inducido químicamente , Enfermedades Neuroinflamatorias/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Oxidantes Fotoquímicos/toxicidad , Estrés Oxidativo , Ratas , Ratas Wistar , Receptores Purinérgicos P2X7/genéticaRESUMEN
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.
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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.
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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).
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Ventrículos Cardíacos/fisiopatología , Hipertensión/patología , Estrés Oxidativo , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Hipertensión Esencial , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Superóxido Dismutasa/sangre , Ultrasonografía , Función Ventricular Izquierda/fisiologíaRESUMEN
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.
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Factores de Transcripción Forkhead/metabolismo , Hipocampo/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ozono/farmacología , Animales , Caspasa 3/metabolismo , Ciclina D2/metabolismo , Activación Enzimática/efectos de los fármacos , Proteína Forkhead Box O3 , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Masculino , Proteínas del Tejido Nervioso , Ozono/administración & dosificación , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Epilepsy is considered one of the most common neurological disorders worldwide. Oxidative stress produced by free radicals may play a role in the initiation and progression of epilepsy; the changes in the mitochondrial and the oxidative stress state can lead mechanism associated with neuronal death pathway. Bioenergetics state failure and impaired mitochondrial function include excessive free radical production with impaired synthesis of antioxidants. This review summarizes evidence that suggest what is the role of oxidative stress on induction of apoptosis in experimental models of epilepsy.
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Epilepsia/metabolismo , Neuronas/patología , Estrés Oxidativo/fisiología , Animales , Apoptosis/fisiología , Modelos Animales de Enfermedad , Epilepsia/genética , Epilepsia/patología , Humanos , Neuronas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Mitochondrial alterations are believed to play a critical role in the pathophysiology of neurodegenerative diseases and in some well-described myopathies. In the present study, we evaluated muscle changes in vivo after blocking the mitochondrial complex II of the respiratory chain by using 3-nitropropionic acid (3-NP). This neurotoxin has been used as a pharmacological tool in animal models to address some of the metabolic modifications that might underlie central neurodegeneration; however, changes in peripheral musculature have not been documented. We believe that skeletal muscles must be affected because their integrity highly depends on oxidative metabolism. Therefore, histochemical, ultrastructural, and biochemical changes were studied in the muscles of mice treated with low doses of 3-NP (15 mg/kg, i.p., for 5 days). 3-NP-treated mice displayed changes in alkaline phosphatase (APase), succinic dehydrogenase (SDH), and cytochrome c oxidase (COX) levels in the gracilis and gastrocnemius muscles. These changes were statistically significant for APase and SDH in both muscles and for COX only in the gastrocnemius. No significant alterations in acetylcholinesterase (AChE) expression were observed in either muscle. Analysis of the muscle ultrastructure revealed mitochondrial atrophy as well as sarcomere and nuclei disorganization. At the biochemical level, nitric oxide (NO) and lipid peroxidation (LPO) changed in the muscles of 3-NP-treated mice, suggesting metabolic alterations due to oxidative stress. Early damage in the striatal tissue and behavioral modifications are also documented.
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Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Neurotoxinas/toxicidad , Nitrocompuestos/toxicidad , Propionatos/toxicidad , Animales , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión , Músculo Esquelético/ultraestructuraRESUMEN
The administration of 3-nitropropionic acid increases reactive oxygen species (ROS). Antioxidant defense mechanisms buffer these ROS converting them into non-damaging compounds. Taurine and vitamins C and E are antioxidants that play a role in the defense against cellular damage. This study examines the antioxidant effect of taurine, vitamin C, and vitamin E on acute hippocampal damage caused by 3-NP. Animals treated with 3-NP increased lipid peroxidation levels and astrocytic damage in the hippocampus. Administration of taurine, vitamin C, and vitamin E partially protected from oxidative damage, indicate that while all substances had antioxidant effects, only taurine showed morphological protection in surviving cells.