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1.
Behav Pharmacol ; 35(6): 338-350, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39051900

RESUMEN

Increasing evidence indicates that neuroinflammation, oxidative stress, and neurotrophic factors play a key role in the pathophysiology of major depressive disorder (MDD). In addition, the attenuation of inflammatory response has been considered a putative mechanism for MDD treatment. PT-31 is an imidazolidine derivative and a putative α2-adrenoceptor agonist that has previously demonstrated antinociceptive activity. The present study aimed to investigate the effect of PT-31 on depressive-like behavior and lipopolysaccharide-induced neurochemical changes. To this end, mice received intraperitoneally saline or lipopolysaccharide (600 µg/kg), and 5 h postinjection animals were orally treated with saline, PT-31 (3, 10, and 30 mg/kg), or fluoxetine (30 mg/kg). Mice were subjected to the open field test (OFT) 6 and 24 h after lipopolysaccharide administration and to the tail suspension test (TST) 24 h postlipopolysaccharide. Subsequently, animals were euthanized, and brains were dissected for neurochemical analyses. The administration of lipopolysaccharide-induced sickness- and depressive-like behaviors, besides promoting an increase in myeloperoxidase activity and a reduction in brain-derived neurotrophic factor (BDNF) levels. Noteworthy, PT-31 3 mg/kg attenuated lipopolysaccharide-induced decreased locomotor activity 6 h after lipopolysaccharide in the OFT. All tested doses of PT-31 significantly reduced the immobility time of animals in the TST and attenuated lipopolysaccharide-induced increased myeloperoxidase activity in the cortex of mice. Our results demonstrate that PT-31 ameliorates behavioral changes promoted by lipopolysaccharide in OFT and TST, which is possibly mediated by attenuation of the inflammatory response.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2 , Antidepresivos , Conducta Animal , Factor Neurotrófico Derivado del Encéfalo , Depresión , Lipopolisacáridos , Animales , Lipopolisacáridos/farmacología , Ratones , Masculino , Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Fluoxetina/farmacología , Relación Dosis-Respuesta a Droga , Prueba de Campo Abierto/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Suspensión Trasera , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/metabolismo
2.
Chemosphere ; 244: 125550, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32050344

RESUMEN

Manganese is a metal often found as an environmental pollutant and very associated with neurological disorders when in high concentrations. However, little is known about the effects that this contaminant can cause when in environmentally relevant concentrations and occurrence, that is, much lower than those commonly studied. So, the aim of the study was to evaluate the effects that environmentally relevant concentrations of this metal would cause in different zebrafish organs (brain, liver, and blood). Acute 96-h and chronic 30-day exposures were performed using the manganese chloride salt as a pollutant. Behavioral alterations of anxiogenic type were observed in the animals after chronic exposures to 4.0 mg L-1 MnCl2, which traveled a greater distance at the bottom of the aquarium. This may be associated with neuronal damages in the telencephalic region responsible for motor and cognitive activity of the fish, observed in animals from the same exposure. In addition, hepatic histopathological damage as vacuolization of hepatocytes and genotoxic damage, identified by comet assay and micronucleus test, was also observed after acute and chronic exposure, especially at the highest pollutant concentrations (8.0 and 16.0 mg L-1 in acute exposure, and 4.0 mg L-1 in chronic exposure. The study reinforces the risk that environmental pollutants pose to the ecosystem, even in low concentrations.


Asunto(s)
Conducta Animal/efectos de los fármacos , Manganeso/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Cloruros , Ensayo Cometa , Daño del ADN , Ecosistema , Hígado/efectos de los fármacos , Compuestos de Manganeso , Pruebas de Micronúcleos , Contaminantes Químicos del Agua/análisis , Pez Cebra/fisiología
3.
Acta toxicol. argent ; 26(3): 99-103, Dec. 2018. ilus, tab
Artículo en Inglés | LILACS | ID: biblio-1001121

RESUMEN

The aim of this study was to assess histopathological alterations in the gills of Astyanax jacuhiensis from different points along the Ijuí River and to determine if these abnormalities can be used as biomarkers in biomonitoring studies. Fish specimens were collected from three sites on the Ijuí River in winter and summer and examined histologically for abnormalities of the secondary lamellae of their gills. For each fish, estimates were made of the frequencies of lamellae with edema, hyperplasia, hypertrophy, epithelium lifting, lamellar fusion or deformation, in addition to the overall frequency of abnormal lamellae and the number of abnormalities per lamella. No differences were observed between sampling points during the winter. In summer the frequency of lamellae with hypertrophy was significantly higher at site 3 (Pirapó) than at site 2 (Santo Ângelo) and the frequency of abnormal lamellae was increased at site 1 (Ijuí) in comparison to site 3. Additionally, all three sample points had a significantly higher value in the winter than in the summer for one of the histological parameters analyzed. These results indicate temporal and spatial variation in the level of contamination of the Ijuí River and also shows that fish gill histopathology can be used for in situ biomonitoring studies.


El agua de la cuenca del río Ijuí, en el sur de Brasil, se utiliza principalmente para irrigar los cultivos y para el abastecimiento público de agua. El objetivo del presente estudio fue evaluar alteraciones histopatológicas en las branquias de Astyanax jacuhiensis en diferentes puntos del Río Ijuí y determinar si tales anormalidades pueden ser usadas como biomarcadores en estudios de biomonitoramiento. Los especímenes fueron recolectados en tres puntos del río durante el invierno y el verano y luego las lamelas secundarias de las branquias fueron examinadas histológicamente para la presencia de anormalidades. Para cada pez se estimaron las frecuencias de lamelas con edema, hiperplasia, hipertrofia, desprendimiento del epitelio, fusión y deformación lamelar. Además, se obtuvieron las frecuencias de lamelas alteradas, así como el número medio de cambios por lamela. No se observaron diferencias entre los puntos de recolección durante el invierno. En el verano, la frecuencia de lamelas con hipertrofia fue significativamente mayor en el punto 3 (Pirapó) que en el punto 2 (Santo Angelo), y el punto 1 (Ijuí) presentó mayor frecuencia de lamelas alteradas que el punto 3. Además, en los tres puntos muestreados, el período de invierno presentó valores superiores para uno de los parámetros histológicos analizados. Estos resultados indican variación espacial y temporal en los niveles de contaminación del Río Ijuí y demuestran que el análisis histológico de las branquias de peces puede ser utilizado en estudios de monitoreo in situ.


Asunto(s)
Biomarcadores/análisis , Peces/anomalías , Branquias/patología , Calidad del Agua , Enfermedades de los Peces/inducido químicamente
4.
Acta toxicol. argent ; 24(2): 97-104, set. 2016. ilus, tab
Artículo en Español | LILACS | ID: biblio-837857

RESUMEN

O estudo avalia a toxicidade, citotoxicidade, genotoxicidade e análises físico-químicas e microbiológicas de amostras de águas coletadas em dois pontos (nascente e foz) do Rio da Ilha - um dos principais afluentes do Rio dos Sinos, RS, Brasil - em dois períodos: inverno (2014) e verão (2015), através do bioensaio com Allium cepa que fornece esses dados através da mensuração das raízes dos bulbos, índice mitótico e presença de aberrações cromossômicas. Os resultados demonstraram níveis de citotoxicidade principalmente na foz do rio, e alguns parâmetros (DBO5, fósforo, alumínio, chumbo, ferro, níquel e coliformes termotolerantes) acima da legislação estabelecida, mesmo a região sofrendo pouco impacto de origem antrópica.


This study evaluates the toxicity, cytotoxicity, genotoxicity and physicochemical and microbiological analysis of water samples collected at sites (source and mouth) of the Ilha River -one of the main tributaries of the Sinos River, RS, Brazil - in winter (2014) and summer (2015), by Allium cepa bioassay which provided the data by measuring the roots of the bulbs, mitotic index and presence of chromosomal aberrations. The results show levels of cytotoxicity especially at the mouth of the river, and some parameters (DBO5, phosphorus, aluminum, lead, iron, nickel and fecal coliforms) above the limits established by the Brazilian legislation, despite the localization of the region in an area under minor anthropic impact.


Asunto(s)
Citotoxinas/toxicidad , Agua Dulce/análisis , Bioensayo/métodos , Brasil , Cebollas/citología , Contaminación de Ríos/análisis
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