RESUMEN
Since 2004, some legacy flame retardants (FRs) were restricted or removed from the European markets due to their concern on human health. Both organophosphorus FRs (OPFRs) and novel brominated FRs (NBFRs) have replaced them because they are presumably safer and less persistent emerging FRs (EFRs) and their exposure is currently occurring in indoor environments at high levels. Little is known about the neurotoxic potential risk of these EFRs in humans. The present study was aimed at assessing the acute neurotoxicity potential of Tris(1, 3-dichloro-2-propyl)phosphate (TDCPP), triphenyl phosphate (TPhP), Bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) on human neuroblastoma cells (SH-SY5Y). SH-SY5Y were exposed to these EFRs at low concentrations -ranging 2.5-20 µM. during 2-24 h. We investigated viability, mitochondrial function, oxidative stress, inflammatory response, as well as neural plasticity and development. The results have demonstrated that selected EFRs (TDCPP, TPhP, EH-TBB and BEH-TBP) did not impair neural function on SH-SY5Y as acute response. To the best of our knowledge, this has been the first study focused on evaluating the neural affection of TPhP on SH-SY5Y cells and of EH-TBB and BEH-TBP on neural cells. We also assessed for the first time almost all endpoints after FR exposure on neural cell lines.
Asunto(s)
Retardadores de Llama , Neuroblastoma , Humanos , Monitoreo del Ambiente , Retardadores de Llama/toxicidad , Polvo/análisis , Organofosfatos/toxicidad , Compuestos Organofosforados/toxicidad , Éteres Difenilos HalogenadosRESUMEN
Radiation therapy represents one of the primary treatment modalities for primary and metastatic brain tumors. Although recent advances in radiation techniques, that allow the delivery of higher radiation doses to the target volume, reduce the toxicity to normal tissues, long-term neurocognitive decline is still a detrimental factor significantly affecting quality of life, particularly in pediatric patients. This imposes the need for the development of prevention strategies. Based on recent evidence, showing that manipulation of the Shh pathway carries therapeutic potential for brain repair and functional recovery after injury, here we evaluate how radiation-induced hippocampal alterations are modulated by the constitutive activation of the Shh signaling pathway in Patched 1 heterozygous mice (Ptch1+/-). Our results show, for the first time, an overall protective effect of constitutive Shh pathway activation on hippocampal radiation injury. This activation, through modulation of the proneural gene network, leads to a long-term reduction of hippocampal deficits in the stem cell and new neuron compartments and to the mitigation of radio-induced astrogliosis, despite some behavioral alterations still being detected in Ptch1+/- mice. A better understanding of the pathogenic mechanisms responsible for the neural decline following irradiation is essential for identifying prevention measures to contain the harmful consequences of irradiation. Our data have important translational implications as they suggest a role for Shh pathway manipulation to provide the therapeutic possibility of improving brain repair and functional recovery after radio-induced injury.
Asunto(s)
Proteínas Hedgehog/genética , Hipocampo/efectos de la radiación , Neurogénesis/genética , Receptor Patched-1/genética , Animales , Astrocitos/metabolismo , Astrocitos/patología , Redes Reguladoras de Genes/efectos de la radiación , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Ratones , Ratones Noqueados , Neurogénesis/efectos de la radiación , Neuronas/metabolismo , Neuronas/efectos de la radiación , Calidad de Vida , Radiación Ionizante , Transducción de Señal/efectos de la radiaciónRESUMEN
Breast cancer (BC) is one of the most important neoplasias among women. Many patients receive radiotherapy (RT), which involves radiation exposure of the thoracic zone, including the heart and blood vessels, leading to the development of cardiovascular disease (CVD) as a long-term side effect. The severity of CVD-related pathologies leads research on assessing novel CVD biomarkers as diagnostic, prognostic or therapeutic agents. Currently, the possible candidates include blood microRNAs (miRNAs). Previous studies have supported a role for miRNA-146a, -155, -221, and -222 in the progression of CVD. Our purpose was to evaluate the RT-induced modulation of the expression of these miRNAs in the blood of women with BC. Pre-RT control and post-RT blood samples were collected, and after miRNA isolation and reverse transcription, the levels of the selected miRNAs were measured by real-time PCR. Our results showed that miRNA-155 exhibited the lowest expression, while miRNA-222 exhibited the highest expression, followed by miRNA-221. The expression of each individual miRNA was positively correlated with that of the others both pre-RT control and post-RT and inversely correlated with age before RT. Furthermore, RT promoted the overexpression of the selected miRNAs. Their levels were also affected by CVD-linked clinical parameters, treatment and BC side. Modulation of the expression of the selected miRNAs together with other risk factors might be associated with the development of future cardiovascular pathologies. Further confirmatory studies are needed to assess their potential as possible biomarkers in the progression of or as therapeutic targets for RT-induced CVD in BC patients.
Asunto(s)
Neoplasias de la Mama/terapia , Enfermedades Cardiovasculares/diagnóstico , Traumatismos por Radiación/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Quimioradioterapia Adyuvante/efectos adversos , Quimioradioterapia Adyuvante/métodos , Progresión de la Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Perfilación de la Expresión Génica , Corazón/efectos de la radiación , Humanos , Mastectomía , MicroARNs/sangre , MicroARNs/metabolismo , Persona de Mediana Edad , Órganos en Riesgo/efectos de la radiación , Traumatismos por Radiación/sangre , Traumatismos por Radiación/etiología , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/métodosRESUMEN
BACKGROUND/AIM: Radiotherapy (RT) can lead to cardiovascular disease (CVD). Evidence suggests that radiation modulates miRNA levels. Our purpose was to assess the acute response to radiation-induced modulation of the expression of miRNA-146a, miRNA-155, miRNA-221, and miRNA-222, inflammatory response and endothelial dysfunction on endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to 2 Gy RT, and intracellular levels of selected miRNAs were measured by real-time polymerase chain reaction at 2 and 24 h. Cytokine and adhesion molecule release were also assessed. RESULTS: Results showed that 2 Gy significantly increased the expression of miRNA-221 and miRNA-222, and reduced the level of miRNA-155 after 2 h; whereas miRNA-146a and miRNA-155 were significantly overexpressed and miRNA-222 was significantly down-regulated at 24 h. Interleukin-8 and soluble vascular cell adhesion molecule 1 levels were not affected by the studied RT. CONCLUSION: RT at 2 Gy modulated expression of selected miRNAs by endothelial cells after 2 and 24 h, which might be related to CVD development in patients who receive RT.
Asunto(s)
Enfermedades Cardiovasculares/metabolismo , Endotelio Vascular/patología , Células Endoteliales de la Vena Umbilical Humana/efectos de la radiación , Inflamación/tratamiento farmacológico , MicroARNs/metabolismo , MicroARNs/efectos de la radiación , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/radioterapia , Adhesión Celular , Citocinas/metabolismo , ADN Complementario/metabolismo , Relación Dosis-Respuesta en la Radiación , Humanos , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
In this pilot study three fractions of particulate matter (PM0.25, PM2.5-0.25, and PM10-2.5) were collected in three environments (classroom, home, and outdoors) in a village located nearby an industrial complex. Time-activity pattern of 20 students attending the classroom was obtained, and the dose of particles reaching the children's lungs under actual environmental conditions (i.e. real dose) was calculated via dosimetry model. The highest PM concentrations were reached in the classroom. Simulations showed that heavy intensity outdoor activities played a major role in PM deposition, especially in the upper part of the respiratory tract. The mass of PM10-2.5 reaching the alveoli was minor, while PM2.5-0.25 and PM0.25 apportion for most of the PM mass retained in the lungs. Consequently, PM2.5-0.25 and PM0.25 were the only fractions used in two subsequent toxicity assays onto alveolar cells (A549). First, a cytotoxicity dose-response assay was performed, and doses corresponding to 5% mortality (LC5) were estimated. Afterwards, two LC-MS metabolomic assays were conducted: one applying LC5, and another applying real dose. A lower estimated LC5 value was obtained for PM0.25 than PM2.5-0.25 (8.08 and 73.7â¯ng/mL respectively). The number of altered features after LC5 exposure was similar for both fractions (39 and 38 for PM0.25 and PM2.5-0.25 respectively), while after real dose exposure these numbers differed (10 and 5 for PM0.25 and PM2.5-0.25 respectively). The most metabolic changes were related to membrane and lung surfactant lipids. This study highlights the capacity of PM to alter metabolic profile of lung cells at conventional environmental levels.
Asunto(s)
Monitoreo del Ambiente , Metabolómica , Material Particulado/toxicidad , Contaminación del Aire Interior/análisis , Niño , Humanos , Pulmón/efectos de los fármacos , Pulmón/patología , Tamaño de la Partícula , Material Particulado/análisis , Proyectos Piloto , Sistema Respiratorio/efectos de los fármacosRESUMEN
137-Cesium (137Cs) is one of the most important distributed radionuclides after a nuclear accident. Humans are usually co-exposed to various environmental toxicants, being Bisphenol-A (BPA) one of them. Exposure to IR and BPA in early life is of major concern, due to the higher vulnerability of developing organs. We evaluate the renal and hepatic effects of low doses of ionizing radiation (IR) and BPA. Sixty male mice (C57BL/6J) were randomly assigned to six experimental groups (n=10) and received a single subcutaneous dose of 0.9% saline solution, 137Cs and/or BPA on postnatal day 10: control, BPA (25 µg/kgbw), Cs4000 (4000 Bq 137Cs/kgbw), Cs8000 (8000 Bq 137Cs/kgbw), BPA/Cs4000 and BPA/Cs8000. At the age of two months, urines (24h) and blood samples were collected from animals of each group to determine biochemical parameters. Finally, kidneys and liver were removed to quantify DNA damage (8-OHdG), as well as to determine CYP1A2 mRNA expression. Data suggest that both BPA and 137Cs induced renal and liver damage evidenced by oxidative stress. However, when there is a co-exposure, it seems that there are compensatory mechanisms that may reverse the damage induced by each toxic itself. Notwithstanding, more studies are necessary to better understand the synergistic mechanisms behind.
Asunto(s)
Compuestos de Bencidrilo/farmacología , Radioisótopos de Cesio/toxicidad , Riñón/efectos de los fármacos , Riñón/efectos de la radiación , Hígado/efectos de los fármacos , Hígado/efectos de la radiación , Fenoles/farmacología , Animales , Animales Recién Nacidos , Compuestos de Bencidrilo/análisis , Radioisótopos de Cesio/análisis , Citocromo P-450 CYP1A2/metabolismo , Exposición a Riesgos Ambientales , Riñón/metabolismo , Hígado/enzimología , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Fenoles/análisisRESUMEN
Nuclear accidents of tremendous magnitude, such as those of Chernobyl (1986) and Fukushima (2011), mean that individuals living in the contaminated areas are potentially exposed to ionizing radiation (IR). However, the dose-response relationship for effects of low doses of radiation is not still established. The present study was aimed at investigating in mice the early effects of low-dose internal radiation exposure on the kidney. Adult male (C57BL/6J) mice were divided into three groups. Two groups received a single subcutaneous (s.c.) doses of cesium (137Cs) with activities of 4000 and 8000Bq/kg bw. A third group (control group) received a single s.c. injection of 0.9% saline. To evaluate acute and subacute effects, mice (one-half of each group) were euthanized at 72h and 10 days post-exposure to 137Cs, respectively. Urine samples were collected for biochemical analysis, including the measurement of F2-isoprostane (F2-IsoP) and kidney injury molecule-1 (KIM-1) levels. Moreover, the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA damage, were measured in renal tissue. Urinary excretion of total protein significantly increased at 72h in mice exposed to Cs4000. Uric acid and lactate dehydrogenase (LDH) decreased significantly at both times post-exposure in animals exposed to Cs8000. After 72h and 10d of exposure to Cs4000, a significant increase in the γ-glutamil transferase (GGT) and N-acetyl-ß-D-glucosaminidase (NAG) activities was observed. In turn, F2-IsoP levels increased -mainly in the Cs4000 group- at 72h post-exposure. Following irradiation (137Cs), the highest level of KIM-1 was corresponded to the Cs4000 group at 72h. Likewise, the main DNA damage was detected in mice exposed to Cs4000, mainly at 10d after irradiation. The alterations observed in several biomarkers suggest an immediate renal damage following exposure to low doses of IR (given as 137Cs). Further investigations are required to clarify the mechanisms involved in the internal IR-induced nephrotoxicity.
Asunto(s)
Riñón/efectos de la radiación , Traumatismos Experimentales por Radiación/patología , Radiación Ionizante , Animales , Biomarcadores/orina , Relación Dosis-Respuesta en la Radiación , Riñón/patología , Riñón/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo , Exposición a la Radiación , Traumatismos Experimentales por Radiación/fisiopatologíaRESUMEN
Radiation therapy is a major cause of long-term complications observed in survivors of pediatric brain tumors. However, the effects of low-doses of ionizing radiation (IR) to the brain are less studied. On the other hand, tobacco is one of the most heavily abused drugs in the world. Tobacco is not only a health concern for adults. It has also shown to exert deleterious effects on fetuses, newborns, children and adolescents. Exposure to nicotine (Nic) from smoking may potentiate the toxic effects induced by IR on brain development. In this study, we evaluated in mice the cognitive effects of concomitant exposure to low doses of internal radiation (137Cs) and Nic during neonatal brain development. On postnatal day 10 (PND10), two groups of C57BL/6J mice were subcutaneously exposed to 137-Cesium (137Cs) (4000 and 8000 Bq/kg) and/or Nic (100 µg/ml). At the age of two months, neurobehavior of mice was assessed. Results showed that exposure to IR-alone or in combination with Nic-increased the anxiety-like of the animals without changing the activity levels. Moreover, exposure to IR impaired learning and spatial memory. However, Nic administration was able to reverse this effect, but only at the low dose of 137Cs.
Asunto(s)
Ansiedad/etiología , Conducta Animal/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Radioisótopos de Cesio/toxicidad , Actividad Motora/fisiología , Nicotina/toxicidad , Memoria Espacial/fisiología , Adolescente , Adulto , Animales , Ansiedad/patología , Encéfalo/efectos de los fármacos , Encéfalo/efectos de la radiación , Humanos , Aprendizaje/efectos de los fármacos , Aprendizaje/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Actividad Motora/efectos de la radiación , Agonistas Nicotínicos/toxicidad , Radiación Ionizante , Memoria Espacial/efectos de los fármacos , Memoria Espacial/efectos de la radiaciónRESUMEN
Therapeutic irradiation of pediatric and adult patients can profoundly affect adult neurogenesis, and cognitive impairment manifests as a deficit in hippocampal-dependent functions. Age plays a major role in susceptibility to radiation, and younger children are at higher risk of cognitive decay when compared to adults. Cranial irradiation affects hippocampal neurogenesis by induction of DNA damage in neural progenitors, through the disruption of the neurogenic microenvironment, and defective integration of newborn neurons into the neuronal network. Our goal here was to assess cellular and molecular alterations induced by cranial X-ray exposure to low/moderate doses (0.1 and 2 Gy) in the hippocampus of mice irradiated at the postnatal ages of day 10 or week 10, as well as the dependency of these phenomena on age at irradiation. To this aim, changes in the cellular composition of the dentate gyrus, mitochondrial functionality, proteomic profile in the hippocampus, as well as cognitive performance were evaluated by a multidisciplinary approach. Our results suggest the induction of specific alterations in hippocampal neurogenesis, microvascular density and mitochondrial functions, depending on age at irradiation. A better understanding of how irradiation impairs hippocampal neurogenesis at low and moderate doses is crucial to minimize adverse effects of therapeutic irradiation, contributing also to radiation safety regulations.
Asunto(s)
Irradiación Craneana/efectos adversos , Hipocampo/efectos de la radiación , Neurogénesis/efectos de la radiación , Factores de Edad , Animales , Femenino , Masculino , Aprendizaje por Laberinto/efectos de la radiación , Ratones , Ratones Endogámicos C57BLRESUMEN
Bisphenol A (BPA) is the most important plasticizer used in many household products such as polycarbonate plastics or epoxy resins. Public and scientific concerns exist regarding the possibility that the neonatal exposure to BPA may contribute to neurobehavioral disorders. On the other hand, there is little information on the effects of low doses of ionizing radiation during critical phases of postnatal brain development, as well as the combination of radiation and environmental chemicals. In this study, C57BL/6J mice were exposed to low doses of internal radiation ((137)Cs), and/or BPA on postnatal day 10 (PND10). At the age of two months, animals were submitted to several tests to assess anxiety, activity, learning, and memory. Results showed that exposure to (137)Cs, alone or in combination with BPA, increased the anxiety-like of the animals without changing the activity levels. Animals exposed to (137)Cs showed impaired learning, and spatial memory, an impairment that was not observed in the groups co-exposed to BPA.
Asunto(s)
Conducta Animal/efectos de los fármacos , Conducta Animal/efectos de la radiación , Compuestos de Bencidrilo/toxicidad , Encéfalo/efectos de los fármacos , Encéfalo/efectos de la radiación , Radioisótopos de Cesio/toxicidad , Fenoles/toxicidad , Plastificantes/toxicidad , Factores de Edad , Animales , Animales Recién Nacidos , Ansiedad/inducido químicamente , Ansiedad/psicología , Encéfalo/crecimiento & desarrollo , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/efectos de la radiación , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/psicología , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Actividad Motora/efectos de la radiación , Memoria Espacial/efectos de los fármacos , Memoria Espacial/efectos de la radiación , Factores de TiempoRESUMEN
Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardant additives in a number of commercial products. Biomonitoring data show that, in recent years, PBDE concentrations have increased rapidly in the bodies of wildlife and humans. Usually, PBDE levels in North America have been reported to be higher than those in Europe and Asia. Moreover, body burden of PBDEs is three- to ninefold higher in infants and toddlers than in adults, showing these last two age groups the highest levels of these compounds, due to exposure via maternal milk and through dust. Tetra-, Penta-, and Hexa-BDEs are the isomers most commonly found in humans. Based on studies on experimental animals, the toxicological endpoints of exposure to PBDEs are likely to be thyroid homeostasis disruption, neurodevelopmental deficits, reproductive changes, and even cancer. Experimental studies in animals and epidemiological observations in humans suggest that PBDEs may be developmental neurotoxicants. Pre- and/or postnatal exposure to PBDEs may cause long-lasting behavioral abnormalities, particularly on motor activity and cognition. This paper is focused on reviewing the current status of PBDEs in the environment, as well as the critical adverse health effects based on the recent studies on the toxic effects of PBDEs.
Asunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/toxicidad , Retardadores de Llama/toxicidad , Éteres Difenilos Halogenados/toxicidad , Bifenilos Polibrominados/toxicidad , Animales , Carga Corporal (Radioterapia) , Enfermedades del Sistema Endocrino/inducido químicamente , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/química , Contaminantes Ambientales/farmacocinética , Femenino , Retardadores de Llama/farmacocinética , Éteres Difenilos Halogenados/química , Éteres Difenilos Halogenados/farmacocinética , Humanos , Enfermedades del Sistema Nervioso/inducido químicamente , Bifenilos Polibrominados/química , Bifenilos Polibrominados/farmacocinética , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamenteRESUMEN
As a result of nuclear power plants accidents such as Chernobyl or Fukushima, some people were exposed to external and internal ionizing radiation (IR). Human brain is highly sensitive to IR during fetal and postnatal period when the molecular processes are not completely finished. Various studies have shown that exposure to low doses of IR causes a higher incidence of cognitive impairment. On the other hand, in industrialized countries, people are daily exposed to a number of toxicant pollutants. Exposure to environmental chemicals, such as paraquat (PQ), may potentiate the toxic effects induced by radiation on brain development. In this study, we evaluated the cognitive effects of concomitant exposure to low doses of internal radiation ((137)Cs) and PQ during neonatal brain development. At the postnatal day 10 (PND10), two groups of mice (C57BL/6J) were exposed to (137)Cs (4000 and 8000 Bq/kg) and/or PQ (7 mg/kg). To investigate the spontaneous behavior, learning, memory capacities and anxiety, behavioral tests were conducted in the offspring at two months of age. The results showed that cognitive functions were not significantly affected when (137)Cs or PQ were administered alone. However, alterations in the working memory and anxiety were detected in mice exposed to (137)Cs combined with PQ.
Asunto(s)
Conducta Animal/efectos de los fármacos , Conducta Animal/efectos de la radiación , Radioisótopos de Cesio/toxicidad , Paraquat/toxicidad , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Encéfalo/efectos de los fármacos , Encéfalo/efectos de la radiación , Cognición/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Aprendizaje/efectos de los fármacos , Aprendizaje/efectos de la radiación , Memoria/efectos de los fármacos , Memoria/efectos de la radiación , Ratones , Ratones Endogámicos C57BLRESUMEN
The purpose of this study was to determine the daily dietary intake of uranium (U) by the general population of Catalonia, Spain. Uranium concentrations were measured in foods widely consumed by the population living in that autonomous community. Food samples were randomly acquired in 12 representative cities of Catalonia. The dietary intake of U was estimated for various age-gender groups: children, adolescents, adults, and seniors. Fish and seafood was the food group showing the highest U concentrations (0.090 µg/g of fresh weight (fw)), followed by dairy products (0.044 µg/g fw). In contrast, the lowest U levels were found in oils and fats (0.003 µg/g fw), while in tubers and milk, U was not detected in any sample. The estimated dietary intake of U for a standard male adult of 70 kg body weight living in Catalonia was 15.48 µg/day. According to the age/gender of the population, the highest dietary intake of U corresponded to children (20.32 µg/day), while senior females was the subgroup with the lowest U intake (10.04 µg/day). Based on the tolerable daily intake established for U, the current dietary intake of this metal by the general population of Catalonia should not mean health risks for any of the different age/gender groups of consumers.
Asunto(s)
Dieta , Análisis de los Alimentos/métodos , Contaminación de Alimentos/análisis , Uranio/análisis , Adolescente , Adulto , Anciano , Animales , Niño , Preescolar , Productos Lácteos/análisis , Exposición a Riesgos Ambientales/análisis , Femenino , Peces/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Alimentos Marinos/análisis , España , Adulto JovenRESUMEN
In this study, we evaluated the effects of BDE-99 on hormone homeostasis, as well as in urinary and serum biochemical parameters of adult male rats. Animals (10 per group) received BDE-99 by gavage at single doses of 0, 0.6 and 1.2mg/kg. Forty-five days after BDE-99 exposure, urine and serum samples were collected for hormonal and biochemical analysis. Oxidative stress (OS) markers in erythrocytes, plasma and urine were also evaluated. Urinary excretion of total protein significantly increased following BDE-99 exposure, while lactate dehydrogenase (LDH), gamma-glutamil transferase (GGT), and N-acetylglucosaminidase (NAG) activities significantly decreased. Liver toxicity was evidenced by elevated serum activities of the enzymes glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP). Following BDE-99 administration, OS markers in erythrocytes showed an increase in superoxide dismutase (SOD) activity, and a reduction in glutathione reductase (GR) activity. In urine, isoprostane levels increased after BDE-99 exposure. The hormonal analysis showed a significant decrease in testosterone and progesterone levels. These results support the hypothesis that BDE-99 interacts with hormonal response. Moreover, BDE-99 administration to adult male rats showed signs of renal and hepatic toxicity.
Asunto(s)
Disruptores Endocrinos/toxicidad , Éteres Difenilos Halogenados/toxicidad , Homeostasis/efectos de los fármacos , Hormonas/metabolismo , Animales , Biomarcadores , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Eritrocitos/metabolismo , Ácidos Grasos Insaturados/química , Hormonas/sangre , Enfermedades Renales/inducido químicamente , Enfermedades Renales/enzimología , Enfermedades Renales/patología , Masculino , Lípidos de la Membrana/química , Lípidos de la Membrana/metabolismo , Estrés Oxidativo/efectos de los fármacos , Oxígeno/sangre , Progesterona/sangre , Ratas , Ratas Sprague-Dawley , Testosterona/sangre , Hormonas Tiroideas/sangreRESUMEN
Little is known about the potential toxicity of polybrominated diphenyl ethers (PBDEs) on hepatic and renal tissues. In this study, we investigated the modifications in endogenous antioxidant capacity and oxidative damage in liver and kidney of rats by exposure to one of the most persistent PBDE congeners, the 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Adult male rats (10 per group) received BDE-99 by gavage at a single dose of 0, 0.6, and 1.2mg/kg body weight. Forty-five days after exposure, liver and kidney were removed and processed to examine the following oxidative stress (OS) markers: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). In liver, BDE-99 significantly increased SOD activity, GSSG levels, and GSSG/GSH ratio, while GSH levels decreased. Moreover, CAT activity was only reduced at the highest BDE-99 dose. In kidney, CAT activity was significantly decreased, while GSSG/GSH ratio significantly increased following BDE-99 exposure at 1.2mg/kg body weight. Histological examination of tissues showed phagolysosomes in the kidneys of BDE-99-exposed rats. The results of this investigation suggest that acute oral BDE-99 exposure causes renal and liver impairment, being oxidative damage a potential mechanism for nephrotoxicity and hepatotoxicity.
Asunto(s)
Éteres Difenilos Halogenados/toxicidad , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Catalasa/metabolismo , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Histocitoquímica , Riñón/enzimología , Riñón/metabolismo , Hígado/enzimología , Hígado/metabolismo , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Estadísticas no Paramétricas , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Polybrominated diphenyl ethers (PBDEs) are used as flame retardants. Although developmental neurotoxicity of PBDEs has been already investigated, little is still known about their potential neurotoxic effects in adulthood. In this study, we assessed the oxidative damage in brain sections and the possible behavioral effects induced by exposure to 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Adult male rats (10/group) received BDE-99 by gavage at single doses of 0, 0.6 or 1.2mg/kg/body weight. Forty-five days after exposure, the following behavioral tests were conducted: open-field activity, passive avoidance and Morris water maze. Moreover, cortex, hippocampus and cerebellum were processed to examine the following oxidative stress (OS) markers: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and thiobarbituric acid reactive substances (TBARS). In cerebellum, BDE-99 significantly decreased SOD, CAT and GR activities at the highest BDE-99 dose. A decrease in CAT and SOD activities was also observed in cortex and hippocampus, respectively. In the behavioral tests, no BDE-99 effects were observed, while histopathological examination of the brain regions was normal. The current results show that the brain antioxidant capacity is affected by BDE-99 exposure, mainly in cerebellum. Oxidative damage could be a mechanism for BDE-99 neurotoxicity in adult rats.
Asunto(s)
Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Retardadores de Llama/toxicidad , Éteres Difenilos Halogenados/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Encéfalo/enzimología , Encéfalo/metabolismo , Catalasa/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Pruebas de ToxicidadRESUMEN
The mechanism of action of sulfasalazine (SASP) in male infertility is not well elucidated. For it, an oxidative stress-like mechanism inductor of infertility was hypothesized. Adult male Sprague-Dawley rats (20/group) were orally administered 0, 300, and 600mg SASP/kg body weight for 14 days. One-half of animals in each group remained an additional period of 14 days without treatment. SASP induced a significant decrease of superoxide dismutase (SOD) and glutathione reductase (GR) at the highest dose in both testis and epididymis. GR remained altered in these tissues within the recovery period. However, an increase in SOD was noted in epididymis. An increase in thiobarbituric acid-reactive substances (TBARS) was noted in all SASP-treated groups. In epididymis, catalase (CAT) significantly increased at 600mg/(kgday). These results suggest that SASP induces oxidative stress, which in turn might act as a possible mechanism of male-induced infertility.
Asunto(s)
Epidídimo/efectos de los fármacos , Fármacos Gastrointestinales/toxicidad , Infertilidad Masculina/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Sulfasalazina/toxicidad , Testículo/efectos de los fármacos , Administración Oral , Animales , Catalasa/metabolismo , Epidídimo/enzimología , Epidídimo/patología , Glutatión Reductasa/metabolismo , Infertilidad Masculina/metabolismo , Infertilidad Masculina/patología , Masculino , Ratas , Ratas Sprague-Dawley , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/citología , Espermatozoides/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Testículo/enzimología , Testículo/patología , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Sulfasalazine (SASP) is a drug commonly used in the treatment of inflammatory bowel diseases (IBD). In this study, the changes in endogenous antioxidant capacity and oxidative damage in liver and kidney of SASP-treated rats were investigated. Adult male Sprague-Dawley rats were orally given 0, 300, or 600 mg SASP/kg body weight for 14 days. One half of the animals in each group remained 14 additional days without SASP treatment. At the end of the experimental period, rats were euthanized and liver and kidney were removed. In both organs, the following stress markers were determined: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid-reactive substances (TBARS). Moreover, histological examination of kidneys showed phagolysosomes after 14 days of SASP withdrawal. A dropsical degeneration was also observed in renal tissue. Oral SASP administration induced a significant increase in TBARS levels in both liver and kidney. After 2 weeks without SASP administration, a recovery of these levels was noted. SOD activity was significantly reduced, while CAT activity significantly increased at 600 mg SASP/(kg day). In kidney, GPx activity significantly increased, while GST activity and GSH levels were significantly reduced at 600 mg SASP/(kg day). These results suggest that in male rats, oxidative damage can be a mechanism for nephro- and hepatotoxicity related with SASP treatment.
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Antiinflamatorios no Esteroideos/efectos adversos , Antioxidantes/metabolismo , Riñón/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Sulfasalazina/efectos adversos , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Riñón/enzimología , Riñón/metabolismo , Riñón/patología , Hígado/enzimología , Hígado/metabolismo , Hígado/patología , Masculino , Ratas , Ratas Sprague-Dawley , Sulfasalazina/administración & dosificaciónRESUMEN
The protective role of exogenous melatonin on U-induced nephrotoxicity was investigated in rats. Animals were given single doses of uranyl acetate dihydrate (UAD) at 5 mg/kg (subcutaneous), melatonin at 10 or 20 mg/kg (intraperitoneal), and UAD (5 mg/kg) plus melatonin (10 or 20 mg/kg), or vehicle (control group). In comparison with the UAD-treated group only, significant beneficial changes were noted in some urinary and serum parameters of rats concurrently exposed to UAD and melatonin. The increase of U excretion after UAD administration was accompanied by a significant reduction in the renal content of U when melatonin was given at a dose of 20 mg/kg. Melatonin also reduced the severity of the U-induced histological alterations in kidney. In renal tissue, the activity of the superoxide dismutase (SOD) and the thiobarbituric acid reactive substances (TBARS) levels increased significantly as a result of UAD exposure. Following UAD administration, oxidative stress markers in erythrocytes showed a reduction in SOD activity and an increase in TBARS levels, which were significantly restored by melatonin administration. In plasma, reduced glutathione (GSH) and its oxidized form (GSSG) were also altered in UAD-exposed rats. However, only the GSSG/GSH ratio was restored to control levels after melatonin treatment. Oxidative damage was observed in kidneys. Melatonin administration partially restored these adverse effects. It is concluded that melatonin offers some benefit as a potential agent to treat acute U-induced nephrotoxicity.
Asunto(s)
Riñón/metabolismo , Riñón/patología , Melatonina/fisiología , Uranio/toxicidad , Animales , Riñón/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Metal toxicity may be associated with increased rates of reactive oxygen species (ROS) generation within the central nervous system (CNS). Although the kidney is the main target organ for uranium (U) toxicity, this metal can also accumulate in brain. In this study, we investigated the modifications on endogenous antioxidant capacity and oxidative damage in several areas of the brain of U-exposed rats. Eight groups of adult male rats received uranyl acetate dihydrate (UAD) in the drinking water at 0, 10, 20, and 40 mg/kg/day for 3 months. Animals in four groups were concurrently subjected to restraint stress during 2h/day throughout the study. At the end of the experimental period, cortex, hippocampus and cerebellum were removed and processed to examine the following stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as U concentrations. The results show that U significantly accumulated in hippocampus, cerebellum and cortex after 3 months of exposure. Moreover, UAD exposure promoted oxidative stress in these cerebral tissues. In cortex and cerebellum, TBARS levels were positively correlated with the U content, while in cerebellum GSSG and GSH levels were positively and negatively correlated, respectively, with U concentrations. In hippocampus, CAT and SOD activities were positively correlated with U concentration. The present results suggest that chronic oral exposure to UAD can cause progressive perturbations on physiological brain levels of oxidative stress markers. Although at the current UAD doses restraint scarcely showed additional adverse effects, its potential influence should not be underrated.