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- ItemAcesso aberto (Open Access)Avaliação dos efeitos do estresse e da administração de corticosterona em diferentes modelos de memória(Universidade Federal de São Paulo (UNIFESP), 2016-05-04) Raya, Juliana [UNIFESP]; Hipólide, Débora Cristina [UNIFESP]; http://lattes.cnpq.br/6303382961871353; http://lattes.cnpq.br/3803119831331341; Universidade Federal de São Paulo (UNIFESP)Memory can be affected by several factors, among them stress. Acute stress, depending on the moment it is applied, may facilitate or impair memory. Chronic stress may affect memory according to their duration and intensity, causing deficit, improvement or no effect. Thus, the objective of this study was to investigate the effects of chronic stress and acute and chronic administration of corticosterone (CORT) in different memory tasks in rats. First, chronic mild stress (ECB) was performed, and animals were evaluated in the Multiple Trial Inhibitory Avoidance task (EIMT). ECB induced an anhedonic behavior in rats, noticed by reduction of sucrose consumption, yet there were no changes in the EIMT performance. We suggest that sucrose may be acting as an attenuator of stress effects. In the second experiment chronic restraint stress was conducted and animals were evaluated in the Morris Water Maze task (TLAM). Rats submitted to chronic restraint stress showed better performance in TLAM than those who did not. Thus, we speculate that stress has not been enough to cause a deficit in memory, but that was moderate to facilitate performance on the task. In other experiments, CORT was administered (40 mg/kg) for 21 days by two routes: orally or subcutaneously, and animals were evaluated in TLAM. It was observed that rats which received vehicle or CORT through voluntary orally path (in a piece of bread) performed the task properly, while animals that received vehicle or CORT subcutaneously showed impairment. We suggest that this discrepancy may be related to the route of administration, since there was no drug effect on any of the experiments. We also evaluated plasmatic CORT 30 minutes after oral administration, and there was a significant increase in the concentration of CORT. Then we found no behavioral changes in the Elevated Plus Maze and Open Field after acute ingestion of CORT (10 and 40 mg/kg). We speculate that this lack of behavioral changes could be explained by the evaluation time on the tasks. In the last experiment, we evaluated the effects of subcutaneous acute administration of CORT in three moments in the EIMT task: pre-training (40 m/kg), after training (40 mg/kg) and pre-test (3, 15 and 40 mg/kg). There were no changes in the performance of animals, and we suggest that the shock employed may have been too high. Furthermore, in the EIMT task animals undergo several training sessions to reach the learning criterion, however, studies commonly use the inhibitory avoidance task with a single session. In conclusion, in this study we present a series of independent experiments that may help in the development of future work involving the effects of stress and CORT administration on memory. We also proposed a refined method of CORT oral administration, which does not present stressors and reduces animal discomfort, contributing to the ethics policy of the 3 R's.
- ItemSomente MetadadadosOral treatment with a rattlesnake native polypeptide crotamine efficiently inhibits the tumor growth with no potential toxicity for the host animal and with suggestive positive effects on animal metabolic profile(Springer Wien, 2018) Campeiro, Joana D. [UNIFESP]; Marinovic, Marcelo P. [UNIFESP]; Carapeto, Fernando Cintra [UNIFESP]; Dal Mas, Caroline [UNIFESP]; Monte, Gabriela Guilherme [UNIFESP]; Porta, Lucas Carvalho [UNIFESP]; Nering, Marcela B. [UNIFESP]; Oliveira, Eduardo B.; Hayashi, Mirian A. F. [UNIFESP]The efficacy of crotamine as antitumoral was first demonstrated by daily intraperitoneal (IP) injections of low doses of this toxin in an animal model bearing melanoma tumors. Significant inhibition of tumor growth and increased lifespan of mice bearing tumor was also noticed after 21 consecutive days of this daily IP administration of crotamine. However, due to the limited acceptance of treatments by IP route in clinical conditions, herein, we evaluated the antitumor effect of this native polypeptide employing the oral route. The efficacy of crotamine in inhibiting the melanoma growth in vivo, even after passing through the gastrointestinal tract of the animal, was confirmed here. In addition, biochemical biomarkers and also histopathological analysis showed both the absence of any potential toxic effects in tissues or organs of the animal in which the highest accumulation of crotamine is expected. Interestingly, a reduction of weight gain was observed mainly in animals with tumor treated with crotamine by IP route, but not by oral administration. Albeit, oral administered crotamine was able to significantly decrease the body weight gain of healthy animals without tumor. Taking advantage of this same experimental animal models receiving crotamine by oral route, it was possible to show metabolic changes as the increased capacity of glucose clearance, which was accompanied by a reduction of the total cholesterol, and by increased high-density lipoprotein levels, both observed mainly in the absence of tumor. Triglycerides and low-density lipoprotein were also significantly decreased, but only in the absence of tumor. Taken together, these data suggest a clear trend for metabolic positive effects and mischaracterize unhealthy condition of animals, with or without tumors, treated with crotamine for 21 days. In addition, this study confirmed the efficacy of crotamine administered by oral route as antitumor agent, which besides the additional advantage of administration convenience and decreased risk of toxic effects, allowed the serendipitous observation of several positive metabolic effects on treated animals.