In vitro evaluation of antileishmanial activity of zerumbon

Autor: Brasil, Anny Ma??za Vargas, https://orcid.org/0000-0001-7191-3999
Přispěvatelé: Pereira, Antonia Maria Ramos Franco, Chagas, Ana Fl??via da Silva, Wyrepkowski, Claudia Dantas Comandolli
Jazyk: portugalština
Rok vydání: 2018
Předmět:
Zdroj: Biblioteca Digital de Teses e Dissertações da UFAM
Universidade Federal do Amazonas (UFAM)
instacron:UFAM
ISSN: 1631-3488
Popis: Submitted by Anny Ma??za Vargas Brasil (mayzabbrasil@gmail.com) on 2021-08-18T20:38:00Z No. of bitstreams: 4 disserta????o_Anny_Maiza.pdf: 1987979 bytes, checksum: 81f218880d115d30e5cece85451ea3aa (MD5) carta de encaminhamento.pdf: 111150 bytes, checksum: 8e1db18e23da564cee21407e832f9084 (MD5) ata de defesa.pdf: 198198 bytes, checksum: 989ea57a72d1de9f8af62f75c9554af8 (MD5) ficha catalogr??fica.pdf: 1852 bytes, checksum: 5bb992660dc239fbc6a2b5e163134889 (MD5) Approved for entry into archive by PPGBIOTEC Biotecnologia (ppgbiotecsecretaria@ufam.edu.br) on 2021-08-18T20:52:03Z (GMT) No. of bitstreams: 4 disserta????o_Anny_Maiza.pdf: 1987979 bytes, checksum: 81f218880d115d30e5cece85451ea3aa (MD5) carta de encaminhamento.pdf: 111150 bytes, checksum: 8e1db18e23da564cee21407e832f9084 (MD5) ata de defesa.pdf: 198198 bytes, checksum: 989ea57a72d1de9f8af62f75c9554af8 (MD5) ficha catalogr??fica.pdf: 1852 bytes, checksum: 5bb992660dc239fbc6a2b5e163134889 (MD5) Rejected by Divis??o de Documenta????o/BC Biblioteca Central (ddbc@ufam.edu.br), reason: Na ficha catalogr??fica, corrigir o g??nero da palavra Coorientador, para Coorientadora (assinalar na caixa). A ficha deve estar inserida na folha 3, do arquivo da disserta????o (Capa, Folha de Rosto, Ficha Catalogr??fica, Ata da Sess??o de Defesa...). on 2021-08-18T21:12:27Z (GMT) Submitted by Anny Ma??za Vargas Brasil (mayzabbrasil@gmail.com) on 2021-08-20T19:25:04Z No. of bitstreams: 4 carta de encaminhamento.pdf: 111150 bytes, checksum: 8e1db18e23da564cee21407e832f9084 (MD5) ata de defesa.pdf: 198198 bytes, checksum: 989ea57a72d1de9f8af62f75c9554af8 (MD5) disserta????o_Anny_Maiza.pdf: 1544497 bytes, checksum: 7b30b22a04c784b1e52d39f33e7d1525 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Approved for entry into archive by PPGBIOTEC Biotecnologia (ppgbiotecsecretaria@ufam.edu.br) on 2021-08-20T19:57:14Z (GMT) No. of bitstreams: 4 carta de encaminhamento.pdf: 111150 bytes, checksum: 8e1db18e23da564cee21407e832f9084 (MD5) ata de defesa.pdf: 198198 bytes, checksum: 989ea57a72d1de9f8af62f75c9554af8 (MD5) disserta????o_Anny_Maiza.pdf: 1544497 bytes, checksum: 7b30b22a04c784b1e52d39f33e7d1525 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Rejected by Divis??o de Documenta????o/BC Biblioteca Central (ddbc@ufam.edu.br), reason: Na pista (palavras-chave), da ficha catalogr??fica: 2. Zerumbona. 3. In vitro. 4. Produtos naturais. (a primeira letra, de cada palavra, deve estar em caixa alta, o mesmo ocorre no caso de siglas). on 2021-08-20T20:51:45Z (GMT) Submitted by Anny Ma??za Vargas Brasil (mayzabbrasil@gmail.com) on 2021-08-20T22:07:33Z No. of bitstreams: 4 carta de encaminhamento.pdf: 111150 bytes, checksum: 8e1db18e23da564cee21407e832f9084 (MD5) ata de defesa.pdf: 198198 bytes, checksum: 989ea57a72d1de9f8af62f75c9554af8 (MD5) disserta????o_Anny_Maiza.pdf: 1544497 bytes, checksum: 7b30b22a04c784b1e52d39f33e7d1525 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Approved for entry into archive by PPGBIOTEC Biotecnologia (ppgbiotecsecretaria@ufam.edu.br) on 2021-08-22T22:18:47Z (GMT) No. of bitstreams: 4 carta de encaminhamento.pdf: 111150 bytes, checksum: 8e1db18e23da564cee21407e832f9084 (MD5) ata de defesa.pdf: 198198 bytes, checksum: 989ea57a72d1de9f8af62f75c9554af8 (MD5) disserta????o_Anny_Maiza.pdf: 1544497 bytes, checksum: 7b30b22a04c784b1e52d39f33e7d1525 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Rejected by Divis??o de Documenta????o/BC Biblioteca Central (ddbc@ufam.edu.br), reason: Na pista (palavras-chave), da ficha catalogr??fica: 2. Zerumbona. 3. In vitro. 4. Produtos naturais. (a primeira letra, de cada palavra, deve estar em caixa alta, o mesmo ocorre no caso de siglas). on 2021-08-23T14:18:00Z (GMT) Submitted by Anny Ma??za Vargas Brasil (mayzabbrasil@gmail.com) on 2021-08-23T14:53:35Z No. of bitstreams: 4 carta de encaminhamento.pdf: 111150 bytes, checksum: 8e1db18e23da564cee21407e832f9084 (MD5) ata de defesa.pdf: 198198 bytes, checksum: 989ea57a72d1de9f8af62f75c9554af8 (MD5) disserta????o_Anny_Maiza .pdf: 1523825 bytes, checksum: 6e50f0f0e721b3bafaae78ad35e4eb29 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Approved for entry into archive by PPGBIOTEC Biotecnologia (ppgbiotecsecretaria@ufam.edu.br) on 2021-08-26T22:58:07Z (GMT) No. of bitstreams: 4 carta de encaminhamento.pdf: 111150 bytes, checksum: 8e1db18e23da564cee21407e832f9084 (MD5) ata de defesa.pdf: 198198 bytes, checksum: 989ea57a72d1de9f8af62f75c9554af8 (MD5) disserta????o_Anny_Maiza .pdf: 1523825 bytes, checksum: 6e50f0f0e721b3bafaae78ad35e4eb29 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Approved for entry into archive by Divis??o de Documenta????o/BC Biblioteca Central (ddbc@ufam.edu.br) on 2021-08-27T01:28:11Z (GMT) No. of bitstreams: 4 carta de encaminhamento.pdf: 111150 bytes, checksum: 8e1db18e23da564cee21407e832f9084 (MD5) ata de defesa.pdf: 198198 bytes, checksum: 989ea57a72d1de9f8af62f75c9554af8 (MD5) disserta????o_Anny_Maiza .pdf: 1523825 bytes, checksum: 6e50f0f0e721b3bafaae78ad35e4eb29 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Made available in DSpace on 2021-08-27T01:28:11Z (GMT). No. of bitstreams: 4 carta de encaminhamento.pdf: 111150 bytes, checksum: 8e1db18e23da564cee21407e832f9084 (MD5) ata de defesa.pdf: 198198 bytes, checksum: 989ea57a72d1de9f8af62f75c9554af8 (MD5) disserta????o_Anny_Maiza .pdf: 1523825 bytes, checksum: 6e50f0f0e721b3bafaae78ad35e4eb29 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-23 FAPEAM - Funda????o de Amparo ?? Pesquisa do Estado do Amazonas American Cutaneous Leishmaniasis (ACL) is a non-contagious infectious disease that affects the protozoa of the genus Leishmania. Approximately 98 have already reported a disease, affecting 12 million people worldwide. The patients with ATL in the clinical setting differed, manifesting in cutaneous and mucosal form. The treatment of the disease in Brazil makes use of drugs of first and second choice, being represented by pentavalent antimonials and like other drugs as the treatment over the years. It is a possibility of attention to be considered as a clinical condition for lesions, a possibility for drugs, a geographical location in which a species of infectious Leishmania was captured. Since then, the drugs have high toxicity, are adverse adverse, some species are needed and are required for parenteral administration. In this context, it is necessary to search for new compositions that have antileishmania activity that demonstrate e-mail and security, facilitating the treatment of the disease. Studies with a zerumba, a sesquiterpene found in Zingiber zerumbet (L.) Roscoe ex Sm., Demonstrated a great accumulation of biomedical properties, focused on a great interest of the scientific community in the possibility of the use of talent for the treatment of cutaneous leishmaniasis. This study is the study of the sigma-aluminum assay in the antigenishmania in antileishmaniasis in the shigellostigotes and amastigotes of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) guyanensis and the cytotoxicity against murine peritoneal macrophages. To evaluate the activity of zerumba against promastigote forms of parasites were exposed to the material under study at concentrations of 0.250 - 0.015 mg / mL, for 48 to 72 hours for L. (V.) Guyanensis and 72 to 96 hours for L. ( L.) amazonensis. A cytotoxic activity against murine peritoneal macrophages was evaluated. For the evaluation of the amastigotes, peritoneal macrophages, the murine ones were submitted to infection by the promastigote forms of the species under study and were exposed at concentrations of 0.250 - 0.031 mg / ml for 48 to 72 hours for L. (V.) Guyanensis and 72 to 96 hours for L. (L.) amazonensis is an evaluation of cell morphology and determination of infection rate. Bioassays indicated that zerumbone shows toxicity to the cellular model under study at concentrations of 0.250 mg / mL and 0.125 mg / mL. Although the mechanism of action is not defined, it is suggested that DNA condensation or oxidative stress lead the cell to undergo apoptosis. It promotes antileishmania activity against promastigotes of both species with EC50 capable of reducing more than 50% of parasite growth during the entire incubation period. The bioassays against amastigote forms for the species L. (L.) amazonensis (72 and 96h) and L. (V.) guyanensis (48 and 72h) presented antileishmania activity and the inhibition of up to 50% of the infection rate was evaluated for both species. For the first time, zerumbone activity against promastigotes and amastigotes of the target species of this study has shown promise for both species, which encourages us to continue the in vivo tests for ACL treatment. A Leishmaniose Tegumentar Americana (LTA) ?? uma doen??a infecciosa n??o contagiosa causada por protozo??rios do g??nero Leishmania. Aproximadamente, 98 j?? notificaram a doen??a, acometendo 12 milh??es de pessoas em todo o mundo. Os pacientes com LTA apresentam quadro cl??nico diferenciado, manifestando-se na forma cut??nea e mucosa. O tratamento da doen??a no Brasil faz o uso das drogas de primeira e segunda escolha, sendo representados pelos antimonais pentavalente e as demais drogas incomporadas como tratamento no decorrer dos anos. ?? necess??rio para determinar a terap??utica a ser aplicada considerar as caracter??sticas cl??nicas das les??es, a susceptibilidade aos medicamentos, a localiza????o geogr??fica em que a infec????o foi adquirida e a esp??cie de Leishmania infectante. Apesar da efic??cia desses f??macos, eles exibem alta toxicidade, efeitos colaterais adversos, resist??ncia a algumas esp??cies e forma de administra????o requerida parenteral. Nesse contexto, faz-se necess??rio a busca por novas composi????es que apresentem atividade antileishmania que demonstre efic??cia e seguran??a, facilitando o tratamento da doen??a. Estudos com a zerumbona, um sesquiterpeno encontrado em Zingiber zerumbet (L.) Roscoe ex Sm., demonstraram que esse composto possui m??ltiplas propriedades biom??dicas, diante disso tem despertado grande interesse da comunidade cient??fica na possibilidade de usar esse composto para tratamento de leishmaniose cut??nea. Neste estudo a zerumbona da Sigma-aldrich foi testada com o objetivo de avaliar a atividade antileishmania in vitro contra formas promastigotas e amastigotas de Leishmania (Leishmania) amazonensis e Leishmania (Viannia) guyanensis e a citotoxicidade frente a macr??fagos peritoneais murinos. Para avalia????o da atividade da zerumbona contra formas promastigotas os parasitas foram expostos ?? subst??ncia em estudo nas concentra????es de 0.250 ??? 0.015 mg/mL, durante 48 a 72 horas para L.(V.) guyanensis e 72 a 96 horas para de L. (L.) amazonensis. Foi avaliada a atividade citot??xica frente a macr??fagos peritoneais murinos. Para avalia????o das formas amastigotas, macr??fagos peritoneais murinos foram submetidos ?? infec????o com formas promastigotas das esp??cies em estudo e posteriormente foram expostos a zerumbona nas concentra????es 0.250 ??? 0.031 mg/mL por 48 a 72 horas para L.(V.) guyanensis e 72 a 96 horas para L. (L.) amazonensis a fim de avaliar a morfologia celular e determinar a taxa de infec????o. Os bioensaios indicaram que a zerumbona apresenta toxicidade para o modelo celular em estudo nas concentra????es de 0.250 mg/mL e 0.125 mg/mL e embora o mecanismo de a????o n??o seja definido sugere-se que seja atrav??s da condensa????o do DNA ou stresse oxidativo o que leva a c??lula a sofrer apoptose. Apresentou atividade antileishmania promissora contra formas promastigotas das duas esp??cies com CE50 capaz de reduzir mais que 50% do crescimento dos parasitas em todo o per??odo de incuba????o. Os bioensaios contra formas amastigotas para as esp??cies L. (L.) amazonensis (72 e 96h) e L. (V.) guyanensis (48 e 72h) apresentaram atividade antileishmania sendo avaliada inibi????o de at?? 50 % da taxa de infec????o para ambas as esp??cies. Pela primeira vez ?? mostrada a atividade da zerumbona contra fromas promastigotas e amastigotas das esp??cies alvo desse estudo sendo promissor para ambas a esp??cies, o que nos encoraja para continuar com os testes in vivo para o tratamento de LTA.
Databáze: OpenAIRE
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