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Universidade Federal Do Tocantins Toxicidade Dos UNIVERSIDADE FEDERAL DO TOCANTINS TOXICIDADE DOS EXTRATOS BRUTO, ACETÁTICO E ALCALOÍDICO DAS FOLHAS DE Psychotria colorata EM RATAS WISTAR Nahuria Rosa Karajá Javaé Tese apresentada como requisito para obtenção do título de Doutora, junto ao Programa de Pós-Graduação em Ciência Animal Tropical da Universidade Federal do Tocantins. Área de Concentração: Produção Animal ARAGUAÍNA 2017 NAHURIA ROSA KARAJÁ JAVAÉ Toxicidade dos extratos bruto, acetático e alcaloídico das folhas de Psychotria colorata em ratas Wistar Tese apresentada como requisito para obtenção do título de Doutora, junto ao Programa de Pós- Graduação em Ciência Animal Tropical da Universidade Federal do Tocantins. Área de Concentração: Produção Animal Orientadora: Profª. Drª. Viviane Mayumi Maruo Co-orientadora: Profª. Drª. Domenica Palomaris Mariano de Sousa ARAGUAÍNA 2017 3 Dedico a Deus, minha família e ao meu povo - Povo Iny. 4 Agradecimentos Agradeço a Deus pelo seu eterno e grandioso amor, amor esse que é a única explicação de sua graça e misericórdia nos mínimos detalhes da minha vida. À Capes e ao CNPq pelo auxílio financeiro à tese. A meus pais Idjarruri Karajá (para sempre em minha memória) e Adaís Rosa Karajá, pelo amor, dedicação, afeto, proteção, conselhos, cuidados sempre prontamente disponibilizados. Pais amados, muito obrigada. A meus irmãos Idjawala e Idjarrina pelo apoio. Em especial ao Idjawala, meu parceiro de guerra. A meus sobrinhos Narubia, Idjahiru, Idjarruri, Marisiru e Loiwá por sempre provocarem espontânea alegria da tia e tirarem em muitos momentos, como mágica, a tensão provocada pelo doutorado. À minha cunhada Hareidja pela cumplicidade e amizade. A meu amado marido, Viviano Iesoru Javaé Karajá (Vivi ou Wade) por seu companheirismo, compreensão e amizade, evidenciando seu amor nos momentos mais difíceis. Marido você é um companheirão! A meu povo – povo Iny. À minha orientadora Profª. Viviane por ter aceitado me orientar também em mais essa etapa. De maneira única ela me ensinou, aconselhou e possibilitou que eu adquirisse conhecimentos que levarei para o resto da vida. À equipe de pesquisa da qual eu fiz parte durante o doutorado, agradeço sinceramente. Às minhas colegas Fernanda, Benta e Nádia pela ajuda. Agradeço em especial a, agora professora, Laiane T. S. Moura por todo apoio e amizade. Às técnicas do laboratório Elis e Gil pelo acompanhamento diário. Agradeço também aos técnicos Liana e Adriano pelas valiosas contribuições. Aos alunos de Iniciação Científica Glads e Nayara em especial a Nayara pelo super auxílio no experimento. Aos Professores Paiva, Laiane, Alberto e Daiene por me darem a honra de comporem a minha banca na defesa da presente tese. 5 Ao Prof. Sandro pelo empréstimo do laboratório sempre que foi necessário e às suas alunas Bárbara e Vanessa pelo pronto atendimento ao longo desse período. Ao senhor Lourival, sua esposa Eva e ao senhor Miguel por possibilitar a coleta da planta. Aos parceiros Antônio Carlos, mais conhecido como ACM, Hélio e Josimar por sempre me ajudarem a resolver as intempéries que surgiram. A amiga Mayara que nunca mediu esforços para me ajudar. A Gil e seu esposo Zé Antônio, Perpétua e Tião por todo auxílio e amizade. À Profª. Isabel Auler (in memorian) por todo apoio e atenção prestados aos estudantes indígenas da UFT. As minhas irmãs em Cristo Wellany, Maiara, Idésia, Luana, Glenda, Camila, Raquel, Raquel gringa, Weyllla, Lourdes, Isadora, Iane, Haylla e Karine pelas muitas risadas nos poucos momentos de descontração. A dona Francisca pelos muitos anos de convivência. Ao pastor Marlécio e sua esposa Fernanda por terem me acompanhado e orado por mim e por minha família durante esse árduo período de doutoramento. Ao pastor Lemos e sua esposa Cidinha pelas orações das 5 da manhã. Aos guardas Valquírio, Zé, Eduardo e Rafael, e aos funcionários terceirizados pelas colaborações, em especial a Lena. A todos que direta e indiretamente tenham contribuído para execução desta pesquisa. Obrigada! 6 SUMÁRIO RESUMO................................................................................................... 10 ABSTRACT............................................................................................... 12 LISTA DE FIGURAS................................................................................. 14 LISTA DE QUADROS............................................................................... 18 LISTA DE TABELAS................................................................................ 19 CAPÍTULO I - Revisão de literatura 1 INTRODUÇÃO…………………………………….…....................... 24 2 REVISÃO DE LITERATURA.........….......…................................. 26 2.1 Rubiaceae .................................................................................... 26 2.2 Gênero Psychotria......................................................................... 29 2.3 Psychotria colorata........................................................................ 30 2.4 Alcaloides...................................................................................... 32 2.5 Compostos fenólicos..................................................................... 35 3 REFERÊNCIAS............................................................................. 39 OBJETIVOS.............................................................................................. 46 1. Objetivo geral....................................................................................... 46 1.1 Objetivos específicos........................................................................ 46 CAPÍTULO II - Toxicidade do extrato bruto das folhas de Psychotria colorata durante a organogênese e desenvolvimento fetal em ratas Wistar RESUMO....................................................................................... 48 ABSTRACT................................................................................... 49 1 INTRODUÇÃO……………………………....................................... 49 2 MATERIAL E MÉTODOS.........….....…………………................... 51 2.1 Obtenção das folhas de P. colorata.............................................. 51 2.2 Obtenção do extrato bruto (EB)..................................................... 52 2.3 Animais.......................................................................................... 52 2.4 Administração do extrato bruto de P. colorata.............................. 52 2.5 Acasalamento e diagnóstico de prenhez....................................... 53 2.6 Estudo de toxicidade embrionária e fetal...................................... 53 2.7 Hemograma................................................................................... 53 2.8 Exames bioquímicos..................................................................... 54 2.9 Necropsia e avaliação anatomo-histopatológica........................... 54 2.10 Análise estatística.......................................................................... 55 3 RESULTADOS.............................................................................. 55 3.1 Rendimento do extrato bruto......................................................... 55 3.2 Consumo de ração, água, peso corporal e ganho de peso........... 55 3.3 Parâmetros hematológicos e bioquímicos..................................... 58 3.4 Peso relativo dos órgãos e avaliação anatomo-histopatológica.... 60 3.5 Parâmetros reprodutivos............................................................... 62 4 DISCUSSÃO................................................................................. 64 5 REFERÊNCIAS............................................................................. 66 7 CAPÍTULO III – Toxicidade subcrônica e reprodutiva do extrato acetático das folhas de P. colorata em ratas Wistar RESUMO....................................................................................... 71 ABSTRACT................................................................................... 71 1 INTRODUÇÃO…………………………………............................... 72 2 MATERIAL E MÉTODOS....…………………………..................... 74 2.1 Obtenção das folhas de P. colorata.............................................. 74 2.2 Obtenção do extrato acetático das folhas de P. colorata ............. 74 2.3 Análise fitoquímica........................................................................ 74 2.3.1 Teste de flavonoides..................................................................... 74 2.3.2 Quantificação de flavonoides totais............................................... 75 2.4 Animais.......................................................................................... 75 2.5 Administração do extrato acetático das folhas de P. colorata....... 76 2.6 Monitoração do ciclo estral............................................................ 76 2.7 Avaliação da fertilidade................................................................. 77 2.8 Hemograma................................................................................... 78 2.9 Exames bioquímicos..................................................................... 78 2.10 Necropsia e avaliação anatomo-histopatológica........................... 78 2.11 Avaliação histomorfométrica da placenta...................................... 79 2.12 Análise estatística.......................................................................... 79 3 RESULTADOS.............................................................................. 81 Rendimento do extrato acetático, caracterização da presença 3.1 flavonoides e quantificação de flavonoides totais........................
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