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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Avaliação toxicológica e antitumoral da aminoquinona ethyl 2- (1,4- dioxo- 1,4- dihydronaphthalen-2-ylamino) acetato em camundongos

MORAES, Thiago Augusto Pereira de 06 June 2013 (has links)
Submitted by (lucia.rodrigues@ufrpe.br) on 2016-06-06T14:27:11Z No. of bitstreams: 1 Thiago Augusto Pereira de Moraes.pdf: 3389646 bytes, checksum: 73f2adc7c0ff85b24e1d8fd67ee82fd7 (MD5) / Made available in DSpace on 2016-06-06T14:29:08Z (GMT). No. of bitstreams: 1 Thiago Augusto Pereira de Moraes.pdf: 3389646 bytes, checksum: 73f2adc7c0ff85b24e1d8fd67ee82fd7 (MD5) Previous issue date: 2013-06-06 / Cytotoxicity of 10 Amino-naphthoquinone (ANQ) was evaluated in cell lines MDA-MB-435 (melanoma), SF-295 (brain) and HCT-8 (colon), all human strains. Among the amino-naphthoquinones tested, five (2a, 9a, 6a, 5a and 7a) have cytotoxicity in cell lines tested. Among these, the sample was the seventh most active, showing IC50 values of 1.84 mg / mL for HCT-8, 1:33 / mL for MDA-MB-435 and 1.80 g / ml in strain SF-295. The same compound produced inhibition of cellular 99.51%, 100.11% and 99.50% for HCT-8, MDA-MB-435 and SF-295, respectively. In the following experiment aimed to determine the toxic effects and the safety threshold of synthetic amino-naphthoquinone ETHYL 2 - (1,4-dioxo-1,4-DIHYDRONAPHTHALEN-2-ylamino) ACETATE, administered in a single dose and different concentrations. For this purpose twenty-four mice (Mus musculus, Swiss albinos) males were divided according to dosage: Group I (treated with the 100μg/Kg aminoquinone (n = 6)), Group II (treated with 200μg/Kg of aminoquinona (n = 6)), Group III (300μg/Kg of aminoquinone treated (n = 6)), Group IV (treated with 600μg/Kg of aminoquinona (n = 6)). The animals were food fasted 6 hours and then treated intraperitoneally with the amino-naphthoquinone according to the prescribed dose. After administration of the doses experimental animals were evaluated for 180 minutes uninterrupted, and then every 24 hours in order to characterize the behavior of the animals through clinical signs for 72 hours. After toxicological evaluation of aminoquinona ETHYL 2 - (1,4-dioxo-1,4-DIHYDRONAPHTHALEN-2-ylamino) ACETATE through analysis of spontaneous activity was found depressing effect on the CNS in a dose-response relationship directly. The calculation of the LD50 test substance showed low levels of toxicity at doses less than 244.1125 ± 23.2883 mg.Kg-1. In subsequent experiments, eighteen mice with solid Ehrlich carcinoma were divided into control group (n = 6) and treated with methotrexate (n = 6; 71.7mg.kg-1) and treated with ethyl 2 - (1,4-dioxo-1,4-dihidronaphthalen-2-ylamino) acetate (n = 6; 20mg.kg-1). Four days after the cells of Ehrlich ascites tumor were implanted subcutaneously and the mice receiving methotrexate amino-naphthoquinone in a single dose. On the 8th day, methotrexate and amino-naphthoquinone 67% inhibited tumor growth by 58% and 67%, respectively compared to the control group. No substantial change in the biochemical and histopathologic findings were observed in the liver and kidneys of animals treated with amino-naphthoquinone. The amino-naphthoquinone ethyl 2 - (1,4-dioxo-1 ,4-dihidronaphthalen-2-ylamino) acetate can be considered a promising drug in cancer therapy. However, future studies should be performed to determine the mechanism of action of this substance. / A citotoxicidade de 10 Amino-naftoquinonas (ANQ) foi avaliada nas linhagens celulares MDA-MB-435 (melanoma), SF-295 (cérebro) e HCT-8 (cólon), todas linhagens humanas. Dentre as amino-naftoquinonas testadas, cinco (2a, 9a, 6a, 5a e 7a) tiveram citotoxicidade nas linhagens celulares testadas. Dentre estas, a amostra 7a foi a mais ativa, evidenciando valores de IC50 de 1.84 μg/mL para HCT-8, 1.33 μg/mL para MDA-MB-435 e 1.80 μg/mL na linhagem SF-295. O mesmo composto produziu inibição celular de 99.51 %, 100 % e 99.50 % para HCT-8, MDA-MB-435 e SF-295, respectivamente. No experimento seguinte objetivou-se determinar os efeitos tóxicos e o limiar de segurança da amino-naftoquinona sintética ETHYL 2-(1,4-DIOXO-1,4-DIHYDRONAPHTHALEN-2-YLAMINO) ACETATE, administrada em dose única e diferentes concentrações. Com este propósito, 24 camundongos (Mus musculus, albinus Swiss) machos foram divididos de acordo com a dosagem: Grupo I (tratados com 100μg/Kg da aminoquinona (n = 6)); Grupo II (tratados com 200μg/Kg de aminoquinona (n = 6)); Grupo III (tratados com 300μg/Kg de aminoquinona (n = 6)); Grupo IV (tratados com 600μg/Kg de aminoquinona (n = 6)). Os animais foram mantidos em jejum alimentar de 6 horas e posteriormente tratados por via intraperitoneal com a amino-naftoquinona, de acordo com as doses estipuladas. Após administração das doses experimentais, os animais foram avaliados por 180 minutos ininterruptos, e posteriormente a cada 24 horas, afim de caracterizar o comportamento dos animais através dos sinais clínicos por 72 horas. Após avaliação toxicológica da aminoquinona ETHYL 2-(1,4-DIOXO-1,4-DIHYDRONAPHTHALEN-2-YLAMINO) ACETATE através da análise de atividade espontânea constatou-se efeito depressor sobre o SNC numa relação dose-resposta direta. O cálculo da DL50 para substância teste demonstrou baixos níveis de toxicidade em dosagens inferiores a 244,1125 ± 23,2883 mg.Kg-1. No experimento subsequente, 18 camundongos com carcinoma sólidos de Ehrlich foram divididos em grupo controle (n=6); tratado com metotrexato (n=6; 71.7mg.kg-1) e tratado com ethyl 2-(1,4-dioxo-1,4-dihidronaphthalen-2-ylamino) acetate (n=6; 20mg.kg-1). Quatro dias após as células do tumor ascítico de Erlich serem implantadas subcutaneamente os camundongos receberam metotrexato e a amino-naftoquinona em dose unica. No 8º dia, o metotrexato e a amino-naftoquinona inibiram 67% o crescimento do tumor em 58% e 67%, respectivamente em relação ao grupo controle. Nenhuma mudança substancial de parâmetros bioquímicos e achados histopatológicos foi observada no fígado e nos rins dos animais tratados com amino-naftoquinona. A amino-naftoquinona ethyl 2-(1,4-dioxo-1,4-dihidronaphthalen-2-ylamino) acetato pode ser considerada uma droga promissora na terapia contra o câncer. Contudo, estudos futuros devem ser realizados na determinação do mecanismo de ação desta substancia.

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