Thesis (M.S.)--University of Wisconsin--Madison, 1996. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 354-362).

Made available in DSpace on 2014-12-17T14:10:27Z (GMT). No. of bitstreams: 1 BrunoMSW_DISSERT.pdf: 2493064 bytes, checksum: 67d2a8f0addf9c48ec5976ed766a8e15 (MD5) Previous issue date: 2012-10-15 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Malaria is a disease of global distribution, recognized by governments around the world as a serious public health problem, affecting more than 109 countries and territories and endangering more than 3.3 billion people. The economic costs of this disease are also relevant: the African continent itself has malaria-related costs of about $ 12 billion annually. Nowadays, in addition to chloroquine, Plasmodium falciparum is resistant to many drugs used in the treatment of malaria, such as amodiaquine, mefloquine, quinine and sulfadoxine-pyrimethamine; resistance of Plasmodium vivax to treatments, although less studied, is also reported. Nature, in general, is responsible for the production of most known organic substances, and the plant kingdom is responsible for the most of the chemical diversity known and reported in the literature. Most medicinal plants commercialized in Brazil, however, are of exotic origin, which makes the search for endemic medicinal plants, besides a patent necessity, a fascinating subject of academic research and development. This study aimed to: (i) verify the antimalarial activity of ethanolic and hydroalcoholic extracts of Boerhavia paniculata Rich. And acetonic extract of Clethra scabra Pers. in Swiss albino mice infected by Plasmodium berghei NK65, (ii) observe possible combined effects between the course of infection by P. berghei NK65 and administration of these extracts in Swiss albino mice, and (iii) conduct a preliminary study of the acute toxicity of these extracts in Swiss albino mice. All extracts notable pharmacological activities - with parasite infections inhibitions ranging from 22% to 54%.These characteristics suggest that the activities are relevant, although comparatively lower than the activity displayed by the positive control group (always above 90%). The general framework of survival analysis demonstrates an overall reduction in survival times for all groups. Necroscopy has not pointed no change in color, shape, size and/or consistency in the evaluated organs - the only exception was the livers of rats submitted to treatment to hydroalcoholic extracts: these organs have been presented in a slightly congestive aspect with mass increasing roughly 28% higher than the other two groups and a p-value of 0.0365. The 250 mg/Kg ethanolic group has been pointed out by the Dunn s post test, as the only class with simultaneous inequalities (p<0.05) between positive and negative control groups. The extracts, notably ethanol extract, have, in fact, a vestigial antimalarial activity, although well below from the ones perceived to chloroquine-treated groups; nevertheless, the survival times of the animals fed with the extracts do not rise by presence of such therapy. Both the toxicopharmacological studies of the synergism between the clinical course of malaria and administration of extracts and the isolated evaluation of toxicity allow us to affirm the absence of toxicity of the extracts at the level of CNS and ANS, as well as their non-influence on food and water consumption patterns, until dosages of 500 mg/Kg. Necroscopic analysis leads us to deduct a possible hepatotoxic effect of hydroalcoholic extract at dosages of 500 mg/Kg, and an innocuous tissue activity of the ethanol extract, in the same dosage. We propose a continuation of the studies of these extracts, with protocol modifications capable of addressing more clearly and objectively their pharmacological and toxicological aspects / A mal?ria ? uma doen?a de distribui??o global, reconhecida por governos de todo o mundo como grave problema de sa?de p?blica, ocorrendo em mais de 109 pa?ses e territ?rios e pondo em risco mais de 3,3 bilh?es de pessoas. Os custos econ?micos da doen?a s?o tamb?m relevantes: apenas o continente africano tem um ?nus de cerca de US$12 bilh?es anuais. Hodiernamente, al?m da cloroquina, o Plasmodium falciparum apresenta resist?ncia aos diversos medicamentos usados na rotina, como amodiaquina, mefloquina, quinina e sulfadoxina-pirimetamina; a resist?ncia de Plasmodium vivax, apesar de menos estudada, tamb?m ? relatada. A natureza, de um modo geral, ? a respons?vel pela produ??o da maioria das subst?ncias org?nicas conhecidas, sendo o reino vegetal respons?vel pela maior parcela da diversidade qu?mica conhecida e registrada na literatura. A maioria das plantas medicinais comercializadas no Brasil, contudo, ? de origem ex?tica, o que torna a busca por plantas medicinais end?micas, al?m de uma patente necessidade, um fascinante assunto de pesquisa acad?mica e de desenvolvimento. Este trabalho teve por objetivo: (i) verificar a atividade antimal?rica dos extratos etan?lico e hidroalco?lico de Boerhavia paniculata Rich. e acet?nico de Clethra scabra Pers. em camundongos albinos Swiss infectados por Plasmodium berghei NK65; (ii) observar poss?veis efeitos combinados entre o curso da infec??o por P. berghei NK65 e a administra??o destes extratos em camundongos albinos Swiss; e (iii) realizar um estudo da toxicidade aguda destes extratos em camundongos albinos Swiss. Notam-se, em todos os extratos, atividades farmacol?gicas not?rias com inibi??es da parasitemia variando de 22% a 54% - caracter?sticas estas que sugerem atividades relevantes, apesar de comparativamente inferior ? atividade apresentada pelo grupo controle positivo (sempre superior a 90%). O quadro geral da an?lise de sobreviv?ncia demonstra uma redu??o global dos tempos de sobrevida para todos os grupos testados. A necroscopia n?o apontou, em um quadro geral, qualquer altera??o de cor, forma, tamanho e/ou consist?ncia nos ?rg?os avaliados nos estudos a ?nica exce??o recaiu sobre os f?gados dos animais submetidos ao extrato hidroalco?lico: estes se apresentaram sob um aspecto levemente congestivo, com aumento de massa cerca de 28% superior aos outros dois grupos e um p-valor de 0,0365. O grupo etan?lico 250 mg/Kg foi apontado, pelo p?s-teste de Dunn, como a ?nica classe com desigualdades simult?neas (p< 0,05) entre os grupos controles positivo e negativo. Os extratos analisados, notadamente o extrato etan?lico, apresentam, de fato, uma atividade antiplasm?dica resquicial, embora muito abaixo da percebida para grupos tratados com cloroquina; n?o obstante, os tempos de sobrevida dos animais submetidos aos tratamentos com os extratos n?o se elevam mediante a presen?a de tal terap?utica. Tanto o estudo t?xico-farmacol?gico do sinergismo entre a evolu??o cl?nica da mal?ria e a administra??o dos extratos quanto a avalia??o isolada de toxicidade nos permitem afirmar a aus?ncia de toxicidade dos extratos em n?vel de SNC e SNA, bem como a n?o influ?ncia destes nos padr?es de consumo h?drico e alimentar, at? as doses de 500 mg/Kg. A an?lise necrosc?pica nos leva ? dedu??o de um poss?vel efeito hepatot?xico do extrato hidroalco?lico, em doses de 500 mg/Kg, e uma atividade tecidual in?cua do extrato etan?lico, em mesma dosagem. Propomos uma continua??o dos estudos destes extratos, com modifica??es protocolares capazes de abordar, de forma mais clara e objetiva, seus aspectos farmacol?gicos e toxicol?gicos