RESUMO
SUMMARY: In this study we aimed to examine the effect of novel vasodilatory drug Riociguat co-administration along resveratrol to recover neurodegeneration in experimental stroke injury. For that purpose, thirty-five adult female rats were divided into five groups (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) of seven animals in each. Animals in Control group did not expose to any application during the experiment and sacrificed at the end of the study. Rats in the rest groups exposed to middle cerebral artery occlusion (MCAO) induced ischemic stroke. MCAO + R group received 30 mg/kg resveratrol, and MCAO + BAY group received 10 mg/kg Riociguat. The MCAO + C group received both drugs simultaneously. The drugs were administered just before the reperfusion, and the additional doses were administered 24h, and 48h hours of reperfusion. All animals in this study were sacrificed at the 72nd hour of experiment. Total brains were received for analysis. Results of this experiment indicated that MCAO led to severe injury in cerebral structure. Bax, IL-6 and IL-1ß tissue levels were up-regulated, but anti-apoptotic Bcl-2 immunoexpression was suppressed (p<0.05). In resveratrol and Riociguat treated animals, the neurodegenerations and apoptosis and inflammation associated protein expressions were improved compared to MCAO group, but the most success was obtained in combined treatment exposed animals in MCAO + C group. This study indicated that the novel soluble guanylate stimulator Riociguat is not only a potent neuroprotective drug in MCAO induced stroke, but also synergistic administration of Riociguat along with resveratrol have potential to increase the neuroprotective effect of resveratrol in experimental cerebral stroke exposed rats.
En este estudio, nuestro objetivo fue examinar el efecto de la coadministración del nuevo fármaco vasodilatador Riociguat junto con resveratrol para recuperar la neurodegeneración en lesiones por ataques cerebrovasculares experimentales. Para ello, se dividieron 35 ratas hembras adultas en cinco grupos (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) de siete animales en cada uno. Los animales del grupo control no fueron sometidos a ninguna aplicación durante el experimento y se sacrificaron al final del estudio. Las ratas de los grupos expuestas a la oclusión de la arteria cerebral media (MCAO) indujeron un ataque cerebrovascular isquémico. El grupo MCAO + R recibió 30 mg/kg de resveratrol y el grupo MCAO + BAY recibió 10 mg/kg de Riociguat. El grupo MCAO + C recibió ambos fármacos simultáneamente. Los fármacos se administraron antes de la reperfusión y las dosis adicionales se administraron a las 24 y 48 horas de la reperfusión. Todos los animales en este estudio fueron sacrificados a las 72 horas del experimento. Se recibieron cerebros totales para su análisis. Los resultados indicaron que la MCAO provocaba lesiones graves en la estructura cerebral. Los niveles tisulares de Bax, IL-6 e IL- 1ß estaban regulados positivamente, pero se suprimió la inmunoexpresión antiapoptótica de Bcl-2 (p <0,05). En los animales tratados con resveratrol y Riociguat, las neurodegeneraciones y las expresiones de proteínas asociadas a la apoptosis y la inflamación mejoraron en comparación con el grupo MCAO, sin embargo el mayor éxito se obtuvo en el tratamiento combinado de animales expuestos en el grupo MCAO + C. Este estudio indicó que el nuevo estimulador de guanilato ciclasa soluble Riociguat no solo es un fármaco neuroprotector potente en el ataque cerebrovascular inducido por MCAO, sino que también la administración sinérgica de Riociguat junto con resveratrol tiene el potencial para aumentar el efecto neuroprotector del resveratrol en ratas experimentales expuestas a un ataque cerebrovascular.
Assuntos
Animais , Feminino , Ratos , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Resveratrol/administração & dosagem , Arteriopatias Oclusivas , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Interleucina-6/análise , Apoptose/efeitos dos fármacos , Fármacos Neuroprotetores , Artéria Cerebral Média , Acidente Vascular Cerebral/patologia , Ativadores de Enzimas/administração & dosagem , Modelos Animais , Quimioterapia Combinada , Interleucina-1beta/análise , Guanilato Ciclase/efeitos dos fármacos , InflamaçãoRESUMO
PURPOSE: To evaluate the neuroprotective effect of resveratrol, urapidil, and a combined administration of these drugs against middle cerebral artery occlusion (MCAO) induced ischemia/reperfusion (IR) injury model in rats. METHODS: Thirty-five rats were divided into five groups of seven animals each. Animals in IR, IR resveratrol (IRr), IR urapidil (IRu), and IR + combination of resveratrol and urapidil (IRc) were exposed to MCAO induced cerebral ischemia reperfusion injury model. Rats in IRr and IRu groups received 30-mg/kg resveratrol and 5-mg/kg urapidil respectively. Animals in IRc received a combined treatment of both drugs. At the end of the study, brain tissues were used for oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), pro-apoptotic caspase-3, anti-apoptotic Bcl-2, and pro-inflammatory tumor necrosis factor-α cytokine level measurements. RESULTS: The MCAO model successfully replicated IR injury with significant histopathological changes, elevated tissue oxidative stress, and upregulated apoptotic and inflammatory protein expression in IR group compared to control group (p < 0.001). All parameters were significantly alleviated in IRr group compared to IR group (all p < 0.05). In IRu group, all parameters except for caspase-3 and Bcl-2 were also significantly different than IR group (all p < 0.05). The IRc group showed the biggest difference compared to IR group in all parameters (all p < 0.001). The IRc had higher superoxide dismutase and Bcl-2 levels, and lower caspase-3 levels compared to both IRr and IRu groups (all p < 0.05). Also, the IRc group had lower MDA and TNF-α levels compared to IRu group (all p < 0.05). CONCLUSIONS: The results indicate that combined treatment of resveratrol and urapidil may be a novel strategy to downregulate neurodegeneration in cerebral IR injury.
Assuntos
Modelos Animais de Doenças , Fármacos Neuroprotetores , Estresse Oxidativo , Traumatismo por Reperfusão , Resveratrol , Estilbenos , Animais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/uso terapêutico , Estilbenos/farmacologia , Quimioterapia Combinada , Ratos Wistar , Infarto da Artéria Cerebral Média/tratamento farmacológico , Resultado do Tratamento , Ratos , Fator de Necrose Tumoral alfa/análise , Superóxido Dismutase/análise , Superóxido Dismutase/metabolismo , Malondialdeído/análise , Malondialdeído/metabolismo , Reprodutibilidade dos Testes , Apoptose/efeitos dos fármacos , Distribuição Aleatória , Isquemia Encefálica/tratamento farmacológico , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Caspase 3/metabolismo , Caspase 3/análiseRESUMO
SUMMARY: Even though morphometric and mineral studies related to the guinea pig (Cavia porcellus) skull have been carried out, this study is the first attempt to evaluate all developmental stages of male and female guinea pigs. This study aims to this study is to create 3D modeling of CT images obtained from the skulls of male and female guinea pigs during the developmental period (prepuberty and the period between puberty and adulthood) and following periods (young adulthood and old adulthood), to analyze some biometric bone data such as volume, surface area and length, and to assess the developmental analysis of the mineral matter change in their skulls. The CT-scanned skulls were transferred to 3D Slicer (5.0.2), which is used for 3D modeling. The surface area and volume were calculated by measuring the measurement points on the models. In addition, the XRF device was used to show elemental ratio changes during different developmental stages. According to metric measurements, a gradual increase was observed during the life period. The metric measurements of the skull bone had a higher measurement value in male guinea pigs than in their female counterparts. While Ca/P ratio increased up to the third group and partially decreased in the fourth group in males, it gradually increased from the first group to the fourth group in females. This study revealed that puberty, adulthood and sex were effective in the physical and chemical characterization of skull bone structure in guinea pigs.
Aunque se han realizado estudios morfométricos y de minerales relacionados con el cráneo del cobayo (Cavia porcellus), esta investigación es el primer intento de evaluar las etapas de desarrollo de cobayos machos y hembras. El objetivo de este estudio fue crear un modelado 3D de imágenes de tomografía computarizada obtenidas de los cráneos de cobayos machos y hembras durante el período de desarrollo (prepubertad y el período entre la pubertad y la edad adulta) y los períodos siguientes (edad adulta joven y edad adulta mayor), para analizar algunos datos biométricos de los huesos, como el volumen, la superficie y la longitud, y además, analizar el cambio de materia mineral en sus cráneos durante el desarrollo. Los cráneos escaneados se transfirieron a 3D Slicer (5.0.2), que se utiliza para el modelado 3D. El área de superficie y el volumen se calcularon midiendo los puntos de medición en los modelos. Además, se utilizó el dispositivo XRF para mostrar los cambios en las proporciones elementales durante diferentes etapas de desarrollo. Según mediciones métricas, se observó un aumento gradual durante el período de vida. Las medidas métricas del hueso del cráneo tuvieron un valor de medición más alto en los cobayos machos que en las hembras. Mientras que la relación Ca/P aumentó hasta el tercer grupo y disminuyó parcialmente en el cuarto grupo en los machos y aumentó gradualmente del primer grupo al cuarto grupo en las hembras. Este estudio reveló que la pubertad, la edad adulta y el sexo fueron efectivos en la caracterización física y química de la estructura ósea del cráneo en cobayos.
Assuntos
Animais , Masculino , Feminino , Cobaias , Crânio/química , Crânio/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Imageamento Tridimensional , Crânio/anatomia & histologia , Espectrometria por Raios X , Minerais/análiseRESUMO
Our study aimed to compare the cecum of German mast geese with other poultry species through macroanatomy and scanning electron microscope (SEM). Adult German geese were used as research material, which were obtained from its breeders and died of various causes. In the study, after determining the macroanatomical features of the German mast goose cecum, it was examined with a scanning electron microscope (JEOL JSM-5600LV) and the general structures were photographed. The craniodorsal of the rectum of German mast geese was shaped with two ceca, giving right and left arms to the cranial symmetrical to each other near the end of the ileum. The macroanatomy of the apex, corpus, and basis cecum parts was examined in the cecum divided into two. In the study, it was determined that villus extensions were sparse in the right and left apex ceci parts in the cecum SEM images of the German mast geese, while the number of the corpus and basis ceci parts was higher. As a result, the macroanatomy and scanning electron microscopic findings of German mast geese cecum were examined in detail and its differences from other poultry species were revealed.(AU)