RESUMO
Oleic acid (OA) is a monounsaturated compound with many health-benefitting properties such as obesity prevention, increased insulin sensitivity, antihypertensive and immune-boosting properties, etc. The aim of this study was to analyze the effect of oleic acid (OA) and some anticancer drugs against oxidative damage induced by nitropropionic acid (NPA) in rat brain. Six groups of Wistar rats were treated as follows: Group 1, (control); group 2, OA; group 3, NPA + OA; group 4, cyclophosphamide (CPP) + OA; group 5, daunorubicin (DRB) + OA; and group 6, dexrazoxane (DXZ) + OA. All compounds were administered intraperitoneally route, every 24 h for 5 days. Their brains were extracted to measure lipoperoxidation (TBARS), H2O2, Ca+2, Mg+2 ATPase activity, glutathione (GSH) and dopamine. Glucose, hemoglobin and triglycerides were measured in blood. In cortex GSH increased in all groups, except in group 2, the group 4 showed the highest increase of this biomarker. TBARS decrease, and dopamine increase in all regions of groups 4, 5 and 6. H2O2 increased only in cerebellum/medulla oblongata of group 5 and 6. ATPase expression decreased in striatum of group 4. Glucose increased in group 6, and hemoglobin increased in groups 4 and 5. These results suggest that the increase of dopamine and the antioxidant effect of oleic acid administration during treatment with oncologic agents could result in less brain injury.
Assuntos
Antineoplásicos , Encéfalo , Glutationa , Ácido Oleico , Estresse Oxidativo , Ratos Wistar , Animais , Estresse Oxidativo/efeitos dos fármacos , Ácido Oleico/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ratos , Masculino , Glutationa/metabolismo , Antineoplásicos/farmacologia , Peróxido de Hidrogênio/metabolismo , Nitrocompostos/farmacologia , Dopamina/metabolismo , Propionatos/farmacologia , Ciclofosfamida , Peroxidação de Lipídeos/efeitos dos fármacos , Daunorrubicina/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Adenosina Trifosfatases/metabolismo , Antioxidantes/farmacologiaRESUMO
Neurotoxicity is a major obstacle in the effectiveness of Cisplatin in cancer chemotherapy. In this process, oxidative stress and inflammation are considered to be the main mechanisms involved in brain and lung toxicity. The aim of the present work was to study the influence of the amount of protein on some oxidative parameters in the brain and lungs of rats treated with Cisplatin (CP) and N-Acetylcysteine (NAC) as neuroprotectors. Four groups of Wistar rats, each containing six animals, were fed with a protein diet at 7% for 15 days. Thereafter, the groups were given either a unique dose of CP® 5 mg/kg or NAC® 5 mg/kg as follows: group 1 (control), NaCl 0.9% vehicle; group 2, CP; group 3, NAC; and group 4, NAC + CP. The animals were sacrificed immediately after the treatments. Blood samples were collected upon sacrifice and used to measure blood triglycerides and glucose. The brain and lungs of each animal were obtained and used to assay lipid peroxidation (TBARS), glutathione (GSH), serotonin metabolite (5-HIAA), catalase, and the activity of Ca+2, and Mg+2 ATPase using validated methods. TBARS, H2O2, and GSH were found to be significantly decreased in the cortex and cerebellum/medulla oblongata of the groups treated with CP and NAC. The total ATPase showed a significant increase in the lung and cerebellum/medulla oblongata, while 5-HIAA showed the same tendency in the cortex of the same group of animals. The increase in 5-HIAA and ATPase during NAC and CP administration resulted in brain protection. This effect could be even more powerful when membrane fluidity is increased, thus proving the efficacy of combined NAC and CP drug therapy, which appears to be a promising strategy for future chemotherapy in malnourished patients.
Assuntos
Acetilcisteína , Cisplatino , Pulmão , Ratos Wistar , Animais , Cisplatino/efeitos adversos , Cisplatino/toxicidade , Acetilcisteína/farmacologia , Ratos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Cérebro/efeitos dos fármacos , Cérebro/metabolismo , Glutationa/metabolismo , Fármacos Neuroprotetores/farmacologia , Antineoplásicos/efeitos adversosRESUMO
Eighty-five percent of the studies of patients with congenital hypothyroidism (CH) treated with Levothyroxine (L-T4) report neuropsychological sequelae throughout life. In neonates and infants, there is a deficit in sensorimotor skills (impaired balance). In preschool and elementary school children and adolescents, there are alterations in intellectual quotient (low scores), language (delayed phonological acquisition), memory (visual, verbal, visuospatial, visuoconstructive, autobiographical, and semantic), sensorimotor skills (impaired fine and gross motor control), and visuoconstructive-visuospatial domain (low scores in spatial location, block design, and object assembly). These neuropsychological domains are also affected in young adults, except for language (adequate verbal fluency) and visuoconstructive-visuospatial domain (no data). The onset and severity of neuropsychological sequelae in patients with treated CH depend on several factors: extrinsic, related to L-T4 treatment and social aspects, and intrinsic, such as severity and etiology of CH, as well as structural and physiological changes in the brain. In this review, we hypothesized that thyroid hormone hyposensitivity (THH) could also contribute to neuropsychological alterations by reducing the effectiveness of L-T4 treatment in the brain. Thus, further research could approach the THH hypothesis at basic and clinical levels to implement new endocrinological and neuropsychological therapies for CH patients.
RESUMO
AIM: The purpose was to measure the effect of Oseltamivir on oxidative biomarkers and dopaminergic and serotonergic systems in brain of rats with induced hypotriglyceridemia by Bezafibrate.Male young Wistar rats were treated as follows: group 1, NaCl 0.9%, (Controls); group 2, Oseltamivir (100 mg/kg); group 3, single dose of Bezafibrate (150 mg/kg); group 4, four dose of Bezafibrate; group 5, single dose of Bezafibrate + Oseltamivir and group 6, four doses of Bezafibrate + Oseltamivir. Drugs were given orally. Triglycerides, Dopamine, 5-hydroxyindoleacetic acid (5-HIAA), Glutathione (GSH), Hydrogen peroxide (H2O2), lipid peroxidation, as well as total ATPase activity were measured using validated methods. RESULTS: Oseltamivir treated animals showed lower GSH and lipid peroxidation levels and an increment in 5-HIAA in the three evaluated brain regions. Treatment with Oseltamivir also reduces H2O2 in the cortex and cerebellum/medulla oblongata. ATPase enzyme increased in these regions in the groups that were administered with Bezafibrate in repeated doses and in combination with Oseltamivir in single dose. Dopamine concentrations decreased in groups treated with Oseltamivir in the three evaluated regions. Also, there was a decrease in dopamine concentrations in the cerebellum/medulla oblongata of the animals treated with the combination of Oseltamivir and Bezafibrate.Innovation and conclusion: Animals with bezafibrate induced hypo-triglyceridemia that received Oseltamivir, either in single or repeated doses, have a higher improvement of their antioxidant activity and also experienced changes in the dopaminergic and serotonergic system in their brain, intending establish the beneficial of joint administration of both drugs in obese patients.
Assuntos
Dopamina , Oseltamivir , Adenosina Trifosfatases/metabolismo , Animais , Bezafibrato/farmacologia , Encéfalo/metabolismo , Glutationa/metabolismo , Peróxido de Hidrogênio/farmacologia , Ácido Hidroxi-Indolacético/farmacologia , Peroxidação de Lipídeos , Masculino , Oseltamivir/farmacologia , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
Several risks for diseases, such as atherosclerosis, renal diseases, and diabetes, have inextricably been linked with obesity. Nowadays, this health-risk-laden disease is being managed with assorted types of drugs, some of which guarantee modest benefits. The chronic inflammatory effect of obesity has a negative effect in insulin signaling, a situation attributable to insulin resistance that culminates in high blood sugar inputs seen in diseases such as type 2 diabetes and metabolic syndrome. Food such as beans with different bioactive compounds could reduce the risk of diabetic complications. Demand for bean products is growing because of its robust contents of several health-promoting components, eg, saponins. Saponins are characterized by containing lower glucose and cholesterol levels and have been doted with antioxidant activities, as well as anti-inflammatory and anti-diabetic effects. In this writing, the attributes of saponins in providing substantial health and nutritional benefits in humans, as well as in improving and ameliorating diabetic complications, were reviewed.
RESUMO
Aim: This study tested the hypothesis that folic acid (FA) modulates biogenic amines and protects the brain against oxidative stress induced by 3-nitropropionic acid (3NPA).Methods: Male Wistar rats received (groups of six) for 5 d: FA (50 mg/kg); 3NPA (10 mg/kg); or FA +3NPA. At last day, rats were sacrificed, and their brain was obtained to measure the levels of dopamine, 5-hydroxiindol acetic acid (5-HIAA). Reduced glutathione (GSH), total ATPase, H2O2 and lipid peroxidation were measured.Results: GSH increased significantly in cortex of rats treated with FA. ATPase increased significantly in cerebellum/medulla oblongata and decreased in cortex of animal treated with 3NPA. 5-HIAA increased in striatum of rats that received 3NPA alone or combined with FA.Conclusion: 3NPA generates free radicals such effect can be counteracted with FA administration since this folate increases antioxidant capacity and modulates biogenic amines.
Assuntos
Antioxidantes/farmacologia , Cerebelo/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Ácido Fólico/farmacologia , Fármacos Neuroprotetores/farmacologia , Nitrocompostos/antagonistas & inibidores , Propionatos/antagonistas & inibidores , Adenosina Trifosfatases/metabolismo , Animais , Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Dopamina/metabolismo , Glutationa/agonistas , Glutationa/metabolismo , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/metabolismo , Ácido Hidroxi-Indolacético/agonistas , Ácido Hidroxi-Indolacético/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Bulbo/efeitos dos fármacos , Bulbo/metabolismo , Nitrocompostos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Propionatos/administração & dosagem , Ratos , Ratos WistarRESUMO
OBJECTIVE: The aim of this study was to evaluate the effect of splenda and stevia on dopamine and 5-HIAA levels, and some biomarkers of oxidative stress in the presence of cytarabine. METHODS: Forty-eight young male Wistar rats each with a weight of 80 g (four weeks of age), distributed in six groups of eight animals each, were treated as follows: group 1, control (NaCl 0.9% vehicle); group 2, cytarabine (0.6 g/kg); group 3, stevia (0.6 g/kg); group 4, cytarabine + stevia; group 5, splenda; and group 6, cytarabine + splenda. Cytarabine was given intravenously (IV) while stevia and splenda were administered orally for five days, using orogastric tube. At the end of treatment, the animals were sacrificed and glucose levels in blood were measured. The brains were dissected for histological analysis and homogenated to measure levels of dopamine, lipid peroxidation (TBARS), serotonin metabolite (5-HIAA), Na+, K+ ATPase activity, and glutathione (GSH), using validated methods. RESULTS: Sweeteners increased the glucose in animals that received cytarabine. Dopamine increased in cortex and decreased in striatum of animals that received stevia alone and combined with cytarabine. 5-HIAA decreased in striatum and cerebellum/medulla oblongata of animals that received sweeteners and cytarabine alone or combined. GSH increased in animals that received sweeteners and decreased with cytarabine. Lipoperoxidation decreased in groups that received sweeteners and cytarabine. Histopathological changes revealed marked degeneration of neuronal cells in animals treated with cytarabine. CONCLUSION: These results show that sweeteners as stevia or splenda may lead to the onset of unfavorable changes in dopamine and 5-HIAA. Antioxidant effects may be involved. Besides, histological changes revealed marked lesions of neuronal cells in experimental animals treated with cytarabine.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Química Encefálica/efeitos dos fármacos , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Citarabina/farmacologia , Edulcorantes/farmacologia , Animais , Dopamina/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Stevia , Sacarose/análogos & derivadosRESUMO
The study tested the hypothesis that cerebrolysin protects the brain from free radicals in rats treated with 3-nitropropionic acid (3-NPA). To address this hypothesis, the levels of dopamine (DA) and some oxidative stress biomarkers were measured after administration of 3-NPA. Young male Fischer rats were treated for three days with cerebrolysin, 3-NPA or both substances. Their brains were extracted, and DA, lipid peroxidation (LP), glutathione (GSH), calcium, and H2O2 were measured using validated methods. In the cortex, hemispheres and cerebellum/medulla oblongata of the group treated with cerebrolysin and 3-NPA, the levels of DA and LP decreased. In addition, calcium and H2O2 levels decreased in the hemispheres of the same group, while GSH increased in cortex. The increased dopamine metabolism due to the administration of cerebrolysin led to increased formation of radical species and oxidative stress, especially when free radicals were generated by 3-NPA.
Assuntos
Aminoácidos/uso terapêutico , Antioxidantes/uso terapêutico , Neurônios Dopaminérgicos/efeitos dos fármacos , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Aminoácidos/efeitos adversos , Animais , Antioxidantes/efeitos adversos , Cálcio/metabolismo , Córtex Cerebelar/efeitos dos fármacos , Córtex Cerebelar/metabolismo , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Cérebro/efeitos dos fármacos , Cérebro/metabolismo , Convulsivantes/efeitos adversos , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Bulbo/efeitos dos fármacos , Bulbo/metabolismo , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/efeitos adversos , Síndromes Neurotóxicas/metabolismo , Nitrocompostos/efeitos adversos , Propionatos/efeitos adversos , Ratos Endogâmicos F344RESUMO
Dopamine is a neurotransmitter that is produced in the substantia nigra, ventral tegmental area, and hypothalamus of the brain. Dysfunction of the dopamine system has been implicated in different nervous system diseases. The level of dopamine transmission increases in response to any type of reward and by a large number of strongly additive drugs. The role of dopamine dysfunction as a consequence of oxidative stress is involved in health and disease. Introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present review focuses on the therapeutic potential of antioxidant compounds as a coadjuvant treatment to conventional neurological disorders is discussed.
Assuntos
Dopamina/metabolismo , Estresse Oxidativo , Animais , Antidepressivos/farmacologia , Dopamina/química , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/metabolismo , Humanos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Receptores Dopaminérgicos/metabolismoRESUMO
Malnutrition contributes to the development of oxidative damage in the central nervous system. The selective administration of nutrients tends to show positive results in individuals who have suffered from malnutrition. To determine the effect of the administration of cocoa powder on the peroxidation of lipids and glutathione level during the nutritional recovery in brain, rats of 21 days old were subjected to a protocol that resembles malnutrition (MN) by feeding them with 60% of the daily food consumption of the control group (WN) and later to nutritional recovery with regular rodent feed (RFR) or added with cocoa (10 g of cocoa powder/kg of regular rodent feed) (CCR). Animals fed with regular rodent food showed significant reduction in brain glutathione: RFR (84.18 ± 6.38 ng/mg protein) vs. CCR (210.61 ± 50.10 ng/mg protein) and WN (186.55 ± 33.18 ng/mg protein), but with similar level to that of MN (92.12 ± 15.60 ng/mg protein). On the contrary, lipid peroxidation in RFR-fed animals increased RFR (1.32 ± 0.2 µM malondialdehyde/g of tissue), CCR (0.86 ± 0.07 µM malondialdehyde/g of tissue), WN (0.89 ± 0.09 µM malondialdehyde/g of tissue), but their thiobarbituric acid reactive substances concentration is similar to that of MN group (1.50 ± 0.2 µM malondialdehyde/g of tissue). Consumption of cocoa powder as a source of antioxidants favors the restoration of the concentration of glutathione and reduces the damage caused by oxidative stress during nutritional recovery in rat brain.
Assuntos
Encéfalo/efeitos dos fármacos , Cacau/química , Desnutrição/terapia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Encéfalo/patologia , Suplementos Nutricionais , Modelos Animais de Doenças , Alimentos , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Desnutrição/complicações , Ratos , Ratos WistarRESUMO
Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis that exposure to severe air pollution plays a role in the immune responses of asymptomatic, apparently healthy children. Blood measurements for markers of immune function, inflammatory mediators, and molecules interacting with the lipopolysaccharide recognition complex were obtained from two cohorts of matched children (aged 9.7 +/- 1.2 years) from southwest Mexico City (SWMC) (n = 66) and from a control city (n = 93) with criteria pollutant levels below current standards. MC children exhibited significant decreases in the numbers of natural killer cells (p = .003) and increased numbers of mCD14+ monocytes (p < .001) and CD8+ cells (p = .02). Lower concentrations of interferon gamma (p = .009) and granulocyte-macrophage colony-stimulating factor (p < .001), an endotoxin tolerance-like state, systemic inflammation, and an anti-inflammatory response were also present in the highly exposed children. C-reactive protein and the prostaglandin E metabolite levels were positively correlated with twenty-four- and forty-eight-hour cumulative concentrations of PM(2.5). Exposure to urban air pollution is associated with immunodysregulation and systemic inflammation in children and is a major health threat.
Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Inflamação/induzido quimicamente , Inflamação/imunologia , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos de Casos e Controles , Criança , Estudos de Coortes , Exposição Ambiental/prevenção & controle , Feminino , Humanos , Inflamação/sangue , Exposição por Inalação/efeitos adversos , Exposição por Inalação/prevenção & controle , Masculino , México , Tamanho da Partícula , Material Particulado , Estudos Retrospectivos , Saúde da População UrbanaRESUMO
We have compared the frequency and types of cancer chemotherapies used in a private hospital and in a government-based hospital in Mexico City. A retrospective study was conducted from January 2005 to December 2007, and therapeutic management determined in 415 cases reviewed by the attending physicians of the oncology service. In the government-based hospital, 60 different types of cancer were found among 273 patients diagnosed. Acute lymphoblastic leukemia (ALL) had the greatest incidence (30%), followed by Hodgkin's lymphoma (9%), retinoblastoma (7%), neuroblastoma (6%), and osteosarcoma (6%). The entire number of chemotherapy sessions was 7575. Drugs most frequently employed included etoposide (577), followed by methotrexate (575), vincristine (483), cyclophosphamide (312), and cytarabine (277). The economic status among these patients was mainly of limited resources and represented 80% of the total number of patients. The types of cancer found in the private hospital were similar, however the drugs used were predominantly cyclophosphamide (416), doxorubicin (382), 5-fluorouracil (368), paclitaxel (237) and cisplatin (128). The types of cancer were similar in both hospitals and reflected the incidence among the entire population in Mexico, since acute lymphoblastic leukemia, Hodgkin's lymphoma and retinoblastoma, were the types most represented. However, the treatment schemes differed; the chemotherapeutic agents used in the private hospital were rather more specific but significantly more expensive than those employed in the government hospital.
Assuntos
Neoplasias/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , México , Estudos RetrospectivosRESUMO
Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.
Assuntos
Poluição do Ar/análise , Encéfalo/fisiopatologia , Cognição/fisiologia , Adolescente , Poluição do Ar/efeitos adversos , Poluição do Ar/economia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Criança , Ciclo-Oxigenase 2/genética , Cães , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Lobo Frontal/fisiopatologia , Gliose/etiologia , Gliose/genética , Gliose/patologia , Humanos , Interleucina-1beta/genética , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Transtornos Mentais/patologia , México/epidemiologia , Testes Neuropsicológicos/estatística & dados numéricos , Material Particulado/análise , Projetos Piloto , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Psicometria/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de RiscoRESUMO
Nutritional support is a critical step in caring for hospitalized patients both to avoid possible metabolic alterations that would worsen the patient's condition, or as a direct result of a particular disease. The purpose of the present study was to describe a procedure for the prescription of total parenteral nutrition (TPN), its administration, monitoring and the complications experienced in a third level hospital in Mexico, as applied to pediatric and adult patients given TPN. The study was carried out for a period of 30 months. TPN was prescribed according to the clinical status of patients. The study reviewed 4,000 parenteral nutrition records from January 2005 to June 2007 (30 months). Based on data here presented a guideline was applied to improve the nutritional support of patients as part of the need to ensure their recuperation during their hospitalization. We observed that TPN must be individualized, based on daily nutrient recommendations, which can be useful to assess the nutritional status of the hospitalized patient with diverse pathologies.
Assuntos
Nutrição Parenteral Total/métodos , Adulto , Criança , Humanos , Pacientes Internados , México , Nutrição Parenteral Total/efeitos adversos , Guias de Prática Clínica como Assunto , Estudos RetrospectivosRESUMO
BACKGROUND: Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. OBJECTIVES: The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O(3) that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. METHODS: We conducted a study of 81 children, 7.9 +/- 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O(3) levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. RESULTS: Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 mum in aerodynamic diameter (PM(2.5)) before endothelin-1 measurement (p = 0.03). CONCLUSIONS: Chronic exposure of children to PM(2.5) is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure.
Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Endotelina-1/sangue , Artéria Pulmonar/efeitos dos fármacos , Adolescente , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Pressão Sanguínea/efeitos dos fármacos , Criança , Cidades , Ecocardiografia Doppler , Feminino , Humanos , Contagem de Leucócitos , Masculino , México , Neutrófilos/efeitos dos fármacos , Ozônio/análise , Ozônio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , Artéria Pulmonar/fisiopatologiaRESUMO
Exposures to particulate matter and gaseous air pollutants have been associated with respiratory tract inflammation, disruption of the nasal respiratory and olfactory barriers, systemic inflammation, production of mediators of inflammation capable of reaching the brain and systemic circulation of particulate matter. Mexico City (MC) residents are exposed to significant amounts of ozone, particulate matter and associated lipopolysaccharides. MC dogs exhibit brain inflammation and an acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by air pollutants. MC children, adolescents and adults have a significant upregulation of cyclooxygenase-2 (COX2) and interleukin-1beta (IL-1beta) in olfactory bulb and frontal cortex, as well as neuronal and astrocytic accumulation of the 42 amino acid form of beta -amyloid peptide (Abeta 42), including diffuse amyloid plaques in frontal cortex. The pathogenesis of Alzheimer's disease (AD) is characterized by brain inflammation and the accumulation of Abeta 42, which precede the appearance of neuritic plaques and neurofibrillary tangles, the pathological hallmarks of AD. Our findings of nasal barrier disruption, systemic inflammation, and the upregulation of COX2 and IL-1beta expression and Abeta 42 accumulation in brain suggests that sustained exposures to significant concentrations of air pollutants such as particulate matter could be a risk factor for AD and other neurodegenerative diseases.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Encéfalo/efeitos dos fármacos , Coração/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Nariz/efeitos dos fármacos , Material Particulado/efeitos adversos , Adolescente , Adulto , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Criança , Cães , Monitoramento Ambiental , Humanos , Pulmão/patologia , Masculino , México , Miocárdio/patologia , Nariz/patologia , Saúde da População UrbanaRESUMO
We examined the effect of experimental malnutrition and diet supplementation of parameters of central nervous system damage. Wistar rats were fed during 30 days and classified as malnourished (MN, 7% protein content diet) or well-nourished (WN, 23% protein content diet), were grouped and treated as follows: I-control; II-SNP (20 microg/kg); IIl-Ivelip (280 mg/kg) and IV-Ivelip + sodium nitroprusside (SNP). Levels of lipid peroxidation (TBARS), glutathione (GSH), tryptophan (Trp) and serotonin (5-HT) were assessed in brain by liquid chromatography. TBARS and GSH levels increased significantly (p < 0.05) in MN vs. WN rats that did not receive Ivelip. No significant differences were observed in TBARS and GSH among rats that received Ivelip or SNP. The weight of rats decreased significantly (p < 0.05) in all MN groups in relation to the WN groups. Hemoglobin (Hb) levels increased significantly (p < 0.05) in MN and WN groups that received Ivelip. 5-HT levels increased significantly (p < 0.05) in all MN groups. Trp levels increased significantly (p < 0.05) in the WN + Ivelip group vs. control. Early malnutrition induces changes in the metabolism of biogenic amines and this condition may promote oxidative injury of the brain.
Assuntos
Química Encefálica/efeitos dos fármacos , Emulsões Gordurosas Intravenosas/farmacologia , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Desnutrição/metabolismo , Nitroprussiato/farmacologia , Serotonina/metabolismo , Óleo de Soja/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta , Hemoglobinas/metabolismo , Masculino , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Desnutrição Proteico-Calórica/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/farmacologia , Triptofano/metabolismoRESUMO
The aim of this study was to analyze the effect of nutritional condition and simulated exposure to ozone on Glutathione (GSH), the activity of Na+/K+ ATPase and lipid peroxidation in rat brain. Male Wistar rats were fed with 7% and 23% protein diets. Two groups were formed for each nutritional condition: one group was exposed for 15 successive days to 0.75 ppm of ozone and the other to air. Subsequently, the brain was dissected in cortex, hemispheres, cerebellum, and brainstem to measure the activity of thiobarbituric acid reactive substances (TBARS), ATPase, and levels of GSH. The activity of Na+/K+ ATPase increased in cerebellum of well-nourished rats exposed to ozone, while total ATPase and TBARS decreased in all studied areas in the malnourished groups. The levels of GSH decreased significantly (P < 0.05) in the brain of rats fed with 7% of protein diet and exposed to ozone but increased in rats fed with normal diet and exposed to ozone. These results suggest that malnutrition causes alterations in the values of Na+/K+ ATPase, total ATPase, GSH, and lipid peroxidation, while ozone contributes to these modifications. As a consequence, both variables are involved in oxidative stress in the rat brain.
Assuntos
Encéfalo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Estado Nutricional/fisiologia , Oxidantes Fotoquímicos/farmacologia , Estresse Oxidativo , Ozônio/farmacologia , Animais , Biomarcadores , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Glutationa/metabolismo , Masculino , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The objective of the present trial was to evaluate the effect of toluene and o-cresol, m-cresol, and p-cresol on serotonin (5-HT), its precursor 5-hydroxytryptophane (5-HTP), Na(+),K(+)-ATPase, total ATPase, and lipid peroxidation (TBARS) in rat brain. Evaluation of lipid peroxidation was realized by means of TBARS, determination of biogenic amines and enzymes assay was carried out in brain homogenate samples using HPLC and spectrophotometry, respectively. Five groups of male Wistar rats (200 g) were treated as follow: control, toluene, o-cresol, m-cresol, and p-cresol groups, which were administered 35 mg/kgi.p. of each compound, the control group was given only glycerine as vehicle. 5-HT and 5-HTP levels increased significantly (p < 0.001) in toluene and o-cresol groups. Lipid peroxidation increased significantly (p < 0.002) in all groups. A significant increase (p < 0.001) of Na(+),K(+)-ATPase was noted in the toluene and o-cresol groups, while this enzyme was reduced in the p-cresol group compared to the control group. Total ATPase showed significant differences in the p-cresol group, compared to the control group. Based in our results, it can be concluded that toluene and all cresols groups may increase lipid peroxidation and consequently induce changes in membrane fluidity.
Assuntos
Encéfalo/efeitos dos fármacos , Cresóis/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Serotonina/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Solventes/farmacologia , Tolueno/farmacologia , Animais , Encéfalo/enzimologia , Encéfalo/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND: The aim of this study was to evaluate effects of pyridoxine and butylated hydroxytoluene (BHT) on lipid peroxidation and on levels of 5-hydroxytryptophan and serotonin. METHODS: Thirty rats (30 days of age) were used in the survey, measuring levels of lipid peroxidation (TBARS), hemoglobin, 5-hydroxytryptophan (5-HTP), and serotonin (5-HT) after intraperitoneal (i.p.) injections of 4 and 10 mg/kg/day of pyridoxine HCl during 20 days and a single dose of 2 microM/kg (440 microg) of BHT. RESULTS: Levels of TBARS and 5-HTP increased considerably (p <0.05) in all vitamin- and/or BHT-treated groups, and 5-HT increased partially (p <0.05) only in B(6) with or without BHT-treated groups compared with control group. CONCLUSIONS: Results suggest that pyridoxine plays a role in tryptophan metabolism, increasing production of 5-HTP.