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1.
Int. j. morphol ; 36(3): 895-900, Sept. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-954204

ABSTRACT

La reserpina es un antipsicótico e hipotensor arterial que reduce significativamente los niveles de monoaminas centrales, y también es utilizada para modelar los cuadros depresivos humanos en animales de laboratorio. Este trabajo estudió, en ratas Wistar machos adolescentes, cómo la reserpina afecta indicadores moleculares de la función testicular, la cual se ha visto alterada en humanos deprimidos. Una semana luego de finalizado el tratamiento con reserpina (4 dosis de 0,0 o 1,0 mg/Kg, cada 2 días) la respuesta ansiosa y depresiva fue evaluada en un laberinto en cruz elevado. Posteriormente, se sacrificaron los animales y disecaron los testículos, los cuales fueron fijados e incluidos en bloques de parafina de donde se obtuvieron cortes histológicos de 6 µm de espesor. Estos se utilizaron para medir el diámetro de los túbulos seminíferos y para medir por inmunohistoquímica el porcentaje de células intersticiales (células de Leydig) positivas a (1) Factor neurotrófico derivado del cerebro, (2) antígeno nuclear de células en proliferación (BDNF y PCNA, respectivamente, por sus siglas en inglés), y a (3) caspasa-3. Se obtuvo también un índice de positividad al receptor de andrógenos en las células intersticiales. La expresión del receptor de andrógeno fue evaluada utilizando una escala semicuantitativa de escores (0, 1, 2 y 3) y el resto de las moléculas por presencia o ausencia de expresión de cada antígeno investigado en 300 células por preparado. Los resultados comportamentales indicaron alteraciones en la respuesta de ansiedad y una significativa depresión motora (e.g., mayor latencia en conductas de escape del sector blanco) en los animales tratados con reserpina. No se observaron diferencias en los diámetros de los túbulos seminíferos ni en la expresión del receptor de andrógeno, mientras que sí se encontró mayor proporción de células intersticiales positivas a BDNF y PCNA, y menor proporción de células positivas a caspasa-3, en los animales tratados. Los resultados corroboran la capacidad de la reserpina para reproducir rasgos comportamentales de la depresión. La administración de la droga, sin embargo, no parece reproducir a nivel testicular los efectos deletéreos encontrados en humanos deprimidos, e incluso los resultados sugieren que la reserpina puede mejorar algunos aspectos de la funcionalidad testicular relacionadas con la actividad de las células intersticiales en ratas.


Reserpine, a drug that depletes central monoamines, has been used as an antipsychotic and arterial hypotensive, and to model depression in animals. The present study analyzed, in adolescent male rats, the effects of chronic reserpine treatment on molecular indexes of testicular function. A week after termination of the treatment (4 doses of 0,0 or 1,0 mg/Kg/every 48 h) the animals were tested for anxiety response and depression patterns in an elevated plus maze. They were then euthanized, their testes dissected, fixed and embedded in paraffin to obtain blocks. Histological sections (6 µm) were obtained and used to measure the diameter of seminiferous tubules and the expression in Leydig cells of Brain-derived neurotrophic factor (BDNF), Proliferating cell nuclear antigen (PCNA), Caspase-3 and androgen receptors, by immunohistochemistry. Behavioral results indicated significant alterations in anxiety responses and a significant motor depression (e.g., greater latency to escape from the white sector). There were no differences between groups in the diameter of seminiferous tubules nor in the androgen receptors positivity. Reserpine-treated animals, however, exhibited more BDNF and PCNA positive cells, and less positive Caspase-3 cells in Leydig cells, than control animals. The results corroborate the efficacy of reserpine to reproduce some of the behavioral components of depression. The drug, however, does not seem to exert in rats the same effects on testicular function that have been found in humans diagnosed with depression. Furthermore the drug seems to enhance some aspects of testicular function related to Leydig cells function in rats.


Subject(s)
Animals , Male , Rats , Reserpine/pharmacology , Testis/drug effects , Antipsychotic Agents/pharmacology , Proliferating Cell Nuclear Antigen/drug effects , Brain-Derived Neurotrophic Factor/drug effects , Leydig Cells/drug effects , Testis/cytology , Immunohistochemistry , Rats, Wistar , Caspase 3/drug effects
2.
Acta cir. bras ; 33(4): 375-385, Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-886280

ABSTRACT

Abstract Purpose: To investigate the effects of melatonin on antioxidant capacity, inflammation and apoptotic cell death (through expression of cleaved-caspase 3) in lung tissue samples of diabetic rats. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group) was made up of healthy rats. Group 2 (diabetes group) received streptozotocin at a dose of 50 mg/kg/day for 5 days.Group 3 (diabetes plus melatonin group) received streptozotocin at a dose of 50 mg/kg/day for 5 days and then they received melatonin at a dose of 20 mg/kg/day between 28thand 35thdays of the study. Results: Tissue MDA and MPO levels were found to be significantly higher in diabetes group compared to control group (p<0.05) whilst administration of melatonin was found to significantly lower this increase down to normal levels (p<0.05). Bronchus associated lymphoid tissue (BALT) was more severe in diabetics whereas administration of melatonin alleviated this hyperplasia. Cleaved caspase 3 activity was severe in hyperplastic BALT in diabetic rats however in lowered down to moderate level when melatonin was administered. Conclusion: The melatonin caused an increase in antioxidant capacity and decreased the expression of cleaved-caspase 3.


Subject(s)
Animals , Male , Diabetes Mellitus, Experimental/pathology , Caspase 3/analysis , Pyroptosis/drug effects , Lung/drug effects , Melatonin/pharmacology , Antioxidants/pharmacology , Superoxide Dismutase/analysis , Time Factors , Immunohistochemistry , Lipid Peroxidation , Catalase/analysis , Random Allocation , Reproducibility of Results , Rats, Sprague-Dawley , Streptozocin , Peroxidase/analysis , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Caspase 3/drug effects , Glutathione/analysis , Lung/metabolism , Lung/pathology , Malondialdehyde/analysis
3.
Biol. Res ; 50: 11, 2017. graf
Article in English | LILACS | ID: biblio-838967

ABSTRACT

BACKGROUND: Cimicifuga racemosa is one of the herbs used for the treatment of climacteric syndrome, and it has been cited as an alternative therapy to estrogen. Apart from hectic fevers, dyspareunia and so on, dry mouth also increase significantly after menopause. It has not yet been reported whether C. racemosa has any impact on the sublingual gland, which may relate to dry mouth. In an attempt to determine this, we have compared the effects of estrogen and C. racemosa on the sublingual gland of ovariectomized rats. RESULTS: HE staining showed that the acinar cell area had contracted and that the intercellular spaces were broadened in the OVX (ovariectomized rats) group, while treatment with estradiol (E2) and iCR (isopropanolic extract of C. racemosa) improved these lesions. Transmission electron microscopy showed that rough endoplasmic reticulum expansion in mucous and serous acinar epithelial cells and apoptotic cells was more commonly seen in the OVX group than in the SHAM (sham-operated rats) group. Mitochondria and plasma membrane infolding lesions in the striated ducts were also observed. These lesions were alleviated by both treatments. It is of note that, in the OVX + iCR group, the volume of mitochondria in the striated duct was larger than in other groups. Immunohistochemical staining showed that the ratio of caspase-3 positive cells was significantly increased in the acinar cells of the OVX group compared with the SHAM group (p < 0.05); and the MA (mean absorbance) of caspase-3 in the striated ducts also increased (p < 0.05). Estradiol decreased the ratio of caspase-3 positive cells and the MA of caspase-3 in striated ducts significantly (p < 0.05). ICR also reduced the ratio of caspase-3 positive cells and the MA in the striated ducts (p < 0.05), but the reduction of the MA in striated ducts was inferior to that of the OVX + E2 group (p < 0.05). CONCLUSION: Both estradiol and iCR can inhibit subcellular structural damage, and down-regulate the expression of caspase-3 caused by ovariectomy, but their effects were not identical, suggesting that both drugs confer a protective effect on the sublingual gland of ovariectomized rats, but that the specific location and mechanism of action producing these effects were different.


Subject(s)
Animals , Female , Rats , Sublingual Gland/drug effects , Plant Extracts/pharmacology , Ovariectomy , Estradiol/pharmacology , Estrogens/pharmacology , Time Factors , Xerostomia/prevention & control , Climacteric/drug effects , Immunohistochemistry , Down-Regulation , Estrogen Replacement Therapy/methods , Reproducibility of Results , Treatment Outcome , Rats, Sprague-Dawley , Apoptosis/drug effects , Microscopy, Electron, Transmission , Caspase 3/analysis , Caspase 3/drug effects , Acinar Cells/drug effects
4.
Invest. clín ; 56(4): 377-388, dic. 2015. ilus
Article in Spanish | LILACS | ID: biblio-829032

ABSTRACT

El ácido valproico, que además de ser un conocido antiepiléptico, una serie de trabajos en los últimos años lo proponen como un agente neuroprotector. En éste trabajo se investigó primeramente, si el ácido valproico protege a las neuronas del daño producido por el estrés oxidativo inducido por la isquemia-reperfusión en el cerebro de ratas sanas sometidas a la oclusión transitoria de la arteria cerebral media derecha; en segundo lugar, se indagó si este fármaco induce cambios en la expresión de Bcl-2 y caspasa 3-activada como un posible mecanismo de acción sobre la muerte celular del tipo apoptótico. La evaluación neurológica de los animales que fueron sometidos a isquemia/reperfusión y recibieron ácido valproico fue mejor que los que no lo recibieron. Por otro lado, los niveles de malondialdehído en el hemisferio cerebral derecho en las ratas tratadas con ácido valproico fueron inferiores a los del mismo hemisferio del grupo control, mientras la cantidad de proteínas carboniladas se redujeron un 67% en comparación al grupo control. Además, se encontró por western blot, que en homogeneizados de tejido cerebral de los animales sometidos a isquemia/reperfusión y que recibieron ácido valproico, hubo un aumento significativo de la densidad de las bandas correspondientes a Bcl-2 y una disminución de caspasa 3-activada en comparación a los que no fueron tratados con este fármaco. Se concluye que el tratamiento con ácido valproico previno el déficit neurológico en ratas sanas sometidas a isquemia-reperfusión, bloqueando el efecto de los radicales libres sobre lípidos y proteínas de la corteza cerebral afectada y se sugiere que posiblemente este fármaco interviene en la muerte por apoptosis inducida durante este tipo de lesión, pudiendo ser una alternativa terapéutica en el tratamiento de la isquemia cerebral.


Valproic acid, apart from being known as an anti-epileptic drug, has been proposed in the past few years, as a neuroprotective agent. The purpose of this study was to investigate firstly, if valproic acid protects the neurons from the damage produced by oxidative stress induced by ischemia-reperfusion in the brain of healthy rats, under the transitory occlusion of the right middle cerebral artery. Secondly it was studied if this antiepileptic drug induces changes on the expression of Bcl-2 and activated caspase-3 as a possible mechanism of action on apoptosis. The neurological evaluation of the animals that were subject to ischemia-reperfusion and received valproic acid was better than the ones who didn’t receive it. On another subject, the levels of malondialdehyde on the right cerebral hemisphere in the rats treated with valproic acid were below the levels of the control group in the same hemisphere, whereas the amount of carbonylated proteins was reduced by 67% compared to the control group. Besides, it was found by western blot, that in homogenized brain tissue of the animals under ischemia-reperfusion which received valproic acid, there was a rise on the density of the bands corresponding to Bcl-2, and a reduction of activated 3-capase in comparison to the ones who were not treated with the antiepileptic drug. It’s concluded that the treatment with valproic acid prevented the neurological deficit in healthy rats under Ischemia-reperfusion, blocking the effect of free radicals on lipids and proteins of the affected brain cortex, and it is suggested that the same drug intervenes on apoptosis induced during this type of damage, being able to be a therapeutic alternative in the treatment of cerebral ischemia.


Subject(s)
Animals , Rats , Reperfusion Injury/prevention & control , Brain Ischemia/prevention & control , Valproic Acid/therapeutic use , Neuroprotective Agents/therapeutic use , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Proto-Oncogene Proteins c-bcl-2/drug effects , Caspase 3/drug effects , Caspase 3/physiology , Rats, Sprague-Dawley
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