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Previous issue date: 2017-02-23 / Atualmente os custos no tratamento de pacientes com doen?as inflamat?rias que progridem de forma sist?mica, com destaque para a sepse, s?o muito elevados e representa a maior causa de morte em unidades de terapia intensiva, n?o cardiol?gica, em todo o mundo. No Brasil, a incid?ncia de pacientes com sepse ? cada vez mais frequente. Apesar dos avan?os farmacol?gicos, tecnol?gicos e cir?rgicos, a mortalidade por sepse e/ou doen?as associadas continua alta em todo o mundo, e por isso se busca alternativas terap?uticas de f?cil acesso e baixo custo para conter o avan?o dessa doen?a. Os produtos naturais v?m desempenhando importante papel na ind?stria farmac?utica, pois algumas dessas subst?ncias agem de forma ben?fica sobre o sistema imunol?gico humano. Nos ?ltimos tempos, h? uma crescente investiga??o das poss?veis propriedades biol?gicas e terap?uticas atribu?das ao ?leo de r?-touro, pois esse ?leo vem sendo utilizado de forma indiscriminada pela popula??o no tratamento de diversas doen?as como bronquite, asma, l?quem escleroso, furunculose, cisto seb?ceo e para cicatriza??o de pele e mucosas. Por?m as poss?veis consequ?ncias no consumo excessivo desse ?leo s?o, o aumento da produ??o de eicosanoides derivados do ?cido araquid?nico proinflamat?rio e a defici?ncia na regula??o hep?tica, predispondo ? esteatose podendo progredir para inflama??o hep?tica e fibrose. Muitas hip?teses se baseiam na atua??o dos compostos presentes no ?leo de r?-touro na modula??o da resposta inflamat?ria, impedindo assim a instala??o de inj?rias teciduais. Dessa forma, a microemuls?o apresenta-se como uma poss?vel alternativa para um novo sistema de libera??o de f?rmacos, com o intuito de diminuir a incid?ncia de hepatoxicidade e protegendo o organismo contra instala??o de les?es teciduais em fun??o do quadro s?ptico. Assim, o presente estudo teve como objetivo avaliar o potencial anti-inflamat?rio do ?leo de r?-touro puro e em um sistema microemulsionado em modelo experimental. Neste estudo, foi preparado e caracterizado um sistema microemulsionado (WIV) e, aplicado em ensaios biol?gicos a fim de avaliar o potencial antiinflamat?rio do ?leo puro e em microemuls?o. Foram utilizados o modelo de sepse, induzida pela t?cnica da CLP (cecal ligant puncture), e a les?o muscular induzida pela formalina. Os ensaios foram realizados em modelos murinos, onde os animais foram separados aleatoriamente em grupos e tratados com o ?leo de r?-touro puro e em microemuls?o, atrav?s da t?cnica de gavage para posterior avalia??o do potencial hepatot?xico e anti-inflamat?rio. Para a an?lise do potencial antiinflamat?rio em modelo de sepse, foram realizadas lavagens bronco alveolares com posterior contagem de c?lulas inflamat?rias e an?lises histopatol?gicas do tecido pulmonar. Para a an?lise no modelo de les?o muscular, foi avaliado extens?o horizontal da pata dos animais, bem como feita a an?lise histopatol?gica do tecido muscular. Para a an?lise do potencial hepatot?xico das subst?ncias, foram avaliados a taxa de sobrevida dos animais p?s-sepse e as an?lises histopatol?gicas dos tecidos hep?ticos dos animais. Quando avaliado a toxicidade do ?leo de r?-touro puro e em sistema microemulsionado, foi observado que no grupo em que foi administrado a microemuls?o (ME), o f?gado teve a arquitetura preservada, mas com sinais cl?nicos de esteatose hep?tica, diferentemente do grupo ?leo de r?-touro puro (OR), que apresentou m?ltiplos focos de necrose hepatoc?tica acompanhado de infiltrado de polimorfonucleares. Esses achados evidenciam um quadro de esteatohepatite, ou seja, um est?gio mais avan?ado e um precursor do carcinoma hep?tico. Quando avaliada a sobrevida dos animais, foi observado que no grupo ME a taxa foi significativamente maior quando comparado ao grupo OR. Quando avaliado o potencial antiinflamat?rio da ME e OR em modelo de sepse, foi observado em ambos os grupos potencial de modula??o da resposta inflamat?ria, visto a capacidade de reduzir de forma significativa (P?0.01) a migra??o de leuc?citos para os pulm?es ap?s a indu??o da sepse. Quando analisado a histologia dos tecidos pulmonares dos animais dos dois grupos, foi verificado intenso desgaste nos animais do grupo OR quando comparados com o grupo ME, onde evidenciou-se pouco comprometimento tecidual. No ensaio de les?o muscular, foi observado que o grupo ME e OR apresentaram bom potencial antiedematog?nico at? a segunda hora da indu??o da les?o, quando comparados ao grupo controle (P?0.01), mas n?o sendo observado diferen?as significativas entre os dois grupos at? a vig?sima quarta hora p?s-les?o. Nas an?lises histol?gicas foram observadas maior desgaste no tecido muscular do grupo OR, com intensa presen?a de infiltrado celular (edema) e comprometimento de fibras musculares, n?o sendo observado a mesma intensidade de inj?ria no grupo ME. Assim, conclui-se que o ?leo de r?-touro puro e em sistema microemulsionado apresentam bom potencial anti-inflamat?rio nos modelos avaliados, embora o ?leo puro tenha apresentado alto potencial hepatot?xico, caracterizando que este em um sistema microemulsionado, se mostra com um poss?vel novo sistema de libera??o de f?rmacos (NSLF). / Current costs of treating patients with systemically progressing inflammatory diseases, especially sepsis, are the leading cause of death in non-cardiological intensive care units worldwide. In Brazil, the incidence of sepsis in patients is becoming more frequent. Despite pharmacological, technological and surgical advances, mortality due to sepsis and/or associated diseases remains high worldwide, hence the search for easily accessible and inexpensive therapeutic alternatives to contain the progression of this disease. Natural products have played an important role in the pharmaceutical industry because some of these substances act in a beneficial way on the human immune system. In recent times, there is a growing investigation of the possible biological and therapeutic properties attributed to bullfrog oil, since this oil has been used indiscriminately by the population in the treatment of various diseases, such as bronchitis, asthma, lichen sclerosus, furunculosis, sebaceous cyst, and for healing of skin and mucous membranes. However, the possible consequences of excessive consumption of this oil are increased production of eicosanoids derived from proinflammatory arachidonic acid and deficiency in hepatic regulation, predisposing to steatosis, which may progress to hepatic inflammation and fibrosis. Many hypotheses are based on the performance of the compounds present in bullfrog oil in the modulation of the inflammatory response, thus preventing the onset of tissue injuries. The microemulsion is presented as a possible alternative to a new drug delivery system, in order to reduce the incidence of hepatotoxicity and protect the organism against the installation of tissue lesions as a function of the septic condition. The present study is aimed to evaluate the anti-inflammatory potential of pure bullfrog oil and a microemulsion system in an experimental model. In this study, a microemulsified system (WIV) was determined and characterized, and applied in biological tests to evaluate the anti-inflammatory potential of pure oil and microemulsion. We used the sepsis model, induced by cecal ligant puncture (CLP) technique, and the formalin-induced muscle injury. The tests were performed in murine models, where the animals were randomly separated into groups and treated with pure bullfrog oil and microemulsion, using the gavage technique for further evaluation of the hepatotoxic and anti-inflammatory potential. For the analysis of the anti-inflammatory potential in a sepsis model, bronchoalveolar lavage was performed with subsequent inflammatory cell counts and histopathological analyzes of lung tissue. For the analysis in the muscle injury model, the horizontal extension of the limbs of the animals was evaluated, as well as the histopathological analysis of the muscle tissue. For the analysis of the hepatotoxic potential of the substances, the post-sepsis survival rate and the histopathological analyzes of the hepatic tissues of the animals were evaluated. When evaluating the toxicity of pure bullfrog oil and in a microemulsion system, it was observed that in the group that received the microemulsion (ME), the liver had the architecture preserved, but with clinical signs of hepatic steatosis, unlike the pure bullfrog oil group, which presented multiple outbreaks of hepatocytic necrosis accompanied by polymorphonuclear infiltrates. These findings indicate a picture of steatohepatitis, that is, a more advanced stage and a precursor of hepatic carcinoma. When evaluating the survival of the animals, it was observed that the ME group survival rate was significantly higher when compared to the oil group. When evaluating the anti-inflammatory potential of the ME and the oil group in a sepsis model, the potential for modulation of the inflammatory response was observed in both groups, since the leukocyte migration to the lungs was significantly reduced (P<0.01) after the induction of sepsis. When analyzing the histology of the lung tissues of the animals of both groups, intense wear was observed in the animals of the oil group, when compared with the ME group, where there was little tissue compromise. In the muscle injury test, it was observed that the ME and oil group had good anti-nematode potential until the second hour of injury induction, when compared to the control group (P<0.01), but no significant differences were observed between the two groups until twenty-fourth hour post-injury. In the histological analyzes, greater wear was observed in the oil group muscle tissue, with an intense presence of cellular infiltrate (edema) and muscle fibers involvement, and the same intensity of injury was not observed in the ME group. Thus, it is concluded that pure bullfrog oil and microemulsion system present good anti-inflammatory potential in the evaluated models, although the pure oil showed high hepatotoxic potential, characterizing that in a microemulsified system, it is shown with a possible new drug delivery system (NSLF).
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/23521 |
| Date | 23 February 2017 |
| Creators | Davim, Andr? Luiz Silva |
| Contributors | 83115951787, http://lattes.cnpq.br/5623374421279476, Santos, Elizeu Antunes dos, 41305655400, http://lattes.cnpq.br/6762251930590306, Maciel, Maria Aparecida Medeiros, 37320165449, http://lattes.cnpq.br/5360188002708095, Cabral, Richard Halti, 16595830809, http://lattes.cnpq.br/7567119410336544, Dantas, Tereza Neuma de Castro, Pereira, M?rcia Rodrigues Pereira |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM DESENVOLVIMENTO E INOVA??O TECNOL?GICA EM MEDICAMENTOS, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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