RESUMEN
Stress exposure can lead to post-traumatic stress disorder (PTSD) in male and female rats. Social-Single Prolonged Stress (SPS) protocol has been considered a potential PTSD model. This study aimed to pharmacologically validate the Social-SPS as a PTSD model in male and female rats. Male and female Wistar rats (60-day-old) were exposed to Social-SPS protocol and treated with fluoxetine (10 mg/Kg) or saline solution intraperitoneally 24 h before euthanasia. Two cohorts of animals were used; for cohort 1, male and female rats were still undisturbed until day 7 post-Social-SPS exposure, underwent locomotor and conditioned fear behaviors, and were euthanized on day 9. Animals of cohort 2 were subjected to the same protocol but were re-exposed to contextual fear behavior on day 14. Results showed that fluoxetine-treated rats gained less body weight than control and Social-SPS in both sexes. Social-SPS effectively increased the freezing time in male and female rats on day eight but not on day fourteen. Fluoxetine blocked the increase of freezing in male and female rats on day 8. Different mechanisms for fear behavior were observed in males, such as Social-SPS increased levels of glucocorticoid receptors and Beclin-1 in the amygdala. Social-SPS was shown to increase the levels of NMDA2A, GluR-1, PSD-95, and CAMKII in the amygdala of female rats. No alterations were observed in the amygdala of rats on day fourteen. The study revealed that Social-SPS is a potential PTSD protocol applicable to both male and female rats.
Asunto(s)
Amígdala del Cerebelo , Miedo , Fluoxetina , Ratas Wistar , Estrés Psicológico , Animales , Masculino , Femenino , Miedo/efectos de los fármacos , Miedo/fisiología , Fluoxetina/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Estrés Psicológico/metabolismo , Ratas , Modelos Animales de Enfermedad , Trastornos por Estrés Postraumático/metabolismo , Trastornos por Estrés Postraumático/psicología , Condicionamiento Clásico/efectos de los fármacos , Condicionamiento Clásico/fisiología , Condicionamiento Psicológico/efectos de los fármacos , Condicionamiento Psicológico/fisiología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Homólogo 4 de la Proteína Discs Large , Receptores AMPARESUMEN
BACKGROUND: Gliomas are the most aggressive malignant tumors of the central nervous system. The diphenyl diselenide [(PhSe)2] is an organoselenium compound that has multiple pharmacological properties. Previous reports showed that (PhSe)2 nanoencapsulation potentiates its in vitro antitumoral action and reduces its toxicity. OBJECTIVE: In this sense, the current study was designed to further evaluate the (PhSe)2 antitumoral effect by a set of in vitro techniques using a glioma cell line as well as by an animal model of gliobastoma. METHODS: For the in vitro tests, the cell viability, propidium iodide uptake and nitrite levels of rat glioma C6 cells were determined after incubation with free (PhSe)2 or (PhSe)2-loaded nanocapsules (NC). The glioblastoma model was induced by implantation of C6 glioma cells in the right striatum of rats. Following, animals were submitted to a repeated intragastric administration treatment with (PhSe)2 or NC (PhSe)2 (1â¯mg/kg/day for 15 days) to assess the possible antitumor effect. MAIN FINDINGS: Both compound forms decreased the C6 glioma cells viability without causing any effect in astrocytes cells (healthy control). Importantly, the NC (PhSe)2 had superior cytotoxic effect than its free form and increased the nitrite content. Independent of the (PhSe)2 forms, the intragastric treatment reduced brain tumor size and caused neither alteration in the plasma renal and hepatic markers of function nor in the parameters of oxidative balance in brain, liver and kidneys. PRINCIPAL CONCLUSIONS: The (PhSe)2 nanoencapsulation improved its cytotoxic effect against C6 glioma cells and both compound forms attenuated the tumor development.
Asunto(s)
Antineoplásicos/farmacología , Derivados del Benceno/farmacología , Modelos Animales de Enfermedad , Glioblastoma/tratamiento farmacológico , Nanocápsulas/química , Compuestos de Organoselenio/farmacología , Animales , Antineoplásicos/química , Astrocitos/efectos de los fármacos , Derivados del Benceno/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ensayos de Selección de Medicamentos Antitumorales , Glioblastoma/patología , Masculino , Nitritos/análisis , Compuestos de Organoselenio/química , Ratas , Ratas WistarRESUMEN
The injection of complete Freund's adjuvant (CFA) in the hindpaw of rodents induces tissue inflammation and nociceptive hypersensitivity. In addition, it has been reported that organoselenium compounds have antinociceptive properties in animal models. The purpose of this study was to investigate the potential antinociceptive effect of bis(phenylimidazoselenazolyl) diselenide (BPIS) in the inflammatory nociception model in mice and its possible mechanism of action. C57BL/6 mice received CFA intraplantar in right hindpaw and the inflammatory response was verified 24h after injection as well as the antinociceptive effect of BPIS. The CFA-induced mechanical allodynia was reversed by BPIS treatment (1mg/kg, p.o.) observed through the von Frey hair test. Additionally, L-arginine (600mg/kg; i.p.), administered before BPIS treatment, blocked its antinociceptive effect. Regarding myeloperoxidase activity, NOx and 3-nitrotyrosine levels, BPIS administration did not reverse alterations observed in the paw of animals injected with CFA. BPIS reversed the increase in spinal NOx content induced by CFA. In the spinal cord, it was also found that CFA induced an increase in malondialdehyde content and a decrease in glutamate uptake, and these alterations were reversed by BPIS. Moreover, BPIS treatment induced an increase in non-protein thiol levels in spinal cord of animals that received CFA injection. No alterations were found in glutathione peroxidase, reductase and S-transferase activities of experimental groups. The obtained data reinforce the relevance of BPIS as an antinociceptive agent as well as highlight the importance of the nitric oxide pathway in the spinal cord and its antioxidant potential for its mechanism of action.