Avaliação da citotoxicidade, genotoxicidade, antigenotoxicidade e expressão dos genes iNos e COX-2 em ratos tratados com a polpa do fruto de Solanum sessiliflorum Dunal [thesis]

Lívia Cristina Hernandes
Maíra Prado, por serem uma excelente equipe sem a qual a realização deste trabalho não seria possível. Em especial ao Alexandre Ferro Aissa, que desde a iniciação científica esteve ao meu lado sempre disposto a esclarecer qualquer dúvida, sugerindo novas ideias para aprimorar nosso grupo de pesquisa, e à Mara Ribeiro de Almeida, que desde o princípio deste trabalho esteve sempre disposta a me transmitir todo seu conhecimento, como na orientação de cálculos de dosagem, na correção de relatórios,
more » ... eção de relatórios, na participação nos experimentos, enfim. Além de ser essencial na concretização deste estudo, você, Mara, é muito especial em minha vida pela sua amizade, proporcionando vários momentos memoráveis! Ao Luiz Fabiano Aguiar, que sempre escutava com muito carinho e atenção todas as minhas aflições e dúvidas, pelo bom humor e alegria constantes que servem como bálsamo ao meu coração. A todos os meus verdadeiros amigos que sempre me incentivaram com palavras carinhosas, mensagens de ânimo e coragem, especialmente agradeço à Preto (FCFRP/USP), que me acolheram com tanto carinho na graduação e pós-ii ABSTRACT HERNANDES, L.C. Cytotoxicity, genotoxicity and antigenotoxicity evaluations and gene expression of iNos and COX-2 in rats treated with the fruit pulp of Solanum sessiliflorum Dunal. 2013. 90 f. Dissertation (Master). Faculdade de Ciências Farmacêuticas de Ribeirão Preto -Universidade de São Paulo, Ribeirão Preto, 2013. Cubiuzeiro (Solanum sessiliflorum Dunal) is a native plant from Amazonian Forest, used in folk medicine to treat burns and to control cholesterol and blood glucose levels. Phytochemical analysis of the cubiuzeiro fruit, known as maná-cubiu, revealed that its composition exhibits carotenoids, phenolic compounds and vitamins. Due to the few studies that have assessed the biological activity and the presence of compounds with antioxidant properties in this fruit, the objectives of this study were to evaluate the effects of maná-cubiu pulp on genomic stability, oxidative stress parameters and expression of pro-inflammatory genes (iNos and COX-2) in Wistar rats and to determine the presence of chemical elements in the lyophilized pulp by ICP-MS. The animals received lyophilized maná-cubiu pulp (125, 250, 375 or 500 mg/kg b.w.) by gavage for 14 days. On the last day of treatment, saline or doxorubicin (DXR, 16 mg/kg b.w.), used as a genotoxic agent, were administered intraperitoneally, and after 24 hours the animals were euthanized. Peripheral blood and bone marrow were used in the micronucleus test. In the comet assay, liver, heart and peripheral blood cells were analyzed. Liver and heart tissues were used to analyze the thiobarbituric acid reactive substances and reduced glutathione (GSH) and to evaluate the mRNA expression of COX-2 and iNos genes. The results showed that maná-cubiu pulp was not mutagenic or cytotoxic in bone marrow and peripheral blood of the animals. At 250 and 375 mg/kg b.w. doses, the maná-cubiu pulp reduced the number of micronucleated cells induced by DXR in peripheral blood, while only the 375 mg/kg b.w. dose was antimutagenic in bone marrow cells. The maná-cubiu pulp was not genotoxic on liver, heart and peripheral blood cells, and the animals treated with maná-cubiu and DXR exhibited lower levels of DNA damage. At 250, 375 and 500 mg/kg b.w. doses, maná-cubiu pulp was able to reduce lipidic peroxidation induced by DXR on liver cells, however did not change the GSH levels on heart and liver cells. The data obtained by real time polymerase chain reaction (RT-qPCR) from COX-2 gene showed that maná-cubiu pulp did not alter the expression of this gene. Also, the maná-cubiu pulp presented trace elements as zinc, manganese, selenium, copper and chromium, but not in significant amounts. Bioactive compounds in the maná-cubiu pulp as carotenoids and phenolic compounds may be associated with the protective effect in certain tissues and doses of maná-cubiu shown in this study.
doi:10.11606/d.60.2013.tde-24062013-154134 fatcat:rs6rjsdpsjbvrf6vghvyox4dqm