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Avaliação in vivo das propriedades anti-inflamatórias, em modelo de colite, de uma lectinina purificada do medronheiro (Arbutus unedo)
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Resumo(s)
As lectinas são um vasto grupo de proteínas que conseguem ligar-se especificamente a recetores glicosilados. Estão presentes em todos os seres vivos e possuem caraterísticas bioquímicas que as tornam únicas no reconhecimento celular. Estas são excelentes diferenciadoras de células com alterações a nível destes recetores glicosilados, ou seja, reconhecem células com aberrações glicómicas, características dos mais variados processos patológicos, especialmente os tumorais.Tendo em conta as suas caraterísticas bioquímica e as suas capacidades de descodificação de glicocódigos, as lectinas têm sido alvo de intensa investigação biomédica, com grande investimento nas suas capacidades biotecnológicas, com vista à sua aplicação terapêutica.
O carcinoma colorretal é o segundo carcinoma mais prevalente em Portugal, no mundo é o terceiro cancro que mais afeta homens e mulheres. Este é influenciado por fatores não controláveis, como a idade, a genética e o historial de doenças inflamatórias do colón (como é o caso da colite ulcerosa) e por fatores ambientais, como os hábitos alimentares e de exercício físico. Muitas das vezes o processo de desenvolvimento e progressão deste carcinoma passa por alterações genéticas que afetam os mecanismos de proliferação, sobrevivência, migração e invasão celulares, ou por modificações pós-traducionais, como a modificação da glicosilação proteica.
O estudo em questão teve como objetivo dar continuidade a trabalhos já desenvolvidos, que demonstraram que uma lectina purificada de Arbutus unedo evidenciou, in vitro, atividade antitumoral. Neste projeto estudou-se a ação anti-inflamatória desta lectina de A.unedo, em modelo in vivo (modelo de colite em murganhos).
Os resultados dos ensaios in vivo demonstraram que a lectina atenua os efeitos da colite, prevendo-se por isso, a sua ligação aos recetores glicosilados das células do cólon alterado, exibindo especificidade para estes recetores anómalos, fazendo regredir a lesão, provavelmente por um mecanismo de morte das células alteradas. Associado ao facto de que os ensaios com a lectina, em murganhos sem colite, não evidenciaram nenhuma alteração do cólon, mostra que a lectina não revelou especificidade para estes recetores, das células do cólon saudável, uma vez que este tecido não evidenciou nenhuma alteração, concluindo-se assim que esta lectina pode ser específica para os recetores do tecido inflamado.
Lectins are a wide/broad group of proteins which can specifically link themselves to glycosylated receptors. These proteins are present throughout nature and possess biochemical characteristics which make them unique in terms of cellular recognition. They are excellent differentiators of cells in which alterations in terms of these glycosylated receptors can be found. That is to say that these proteins recognise cells with glycomic aberrations which are characteristic of the most varied pathological processes, especially tumoural ones. Their biochemical characteristics and their capacity to decode glycocodes, lectins have been targeted to intense biomedical research, with great investment in their biotechnological capacities, aiming at their therapeutic applications. Colorectal cancer is the second most prevailing cancer in Portugal, and the third one which most affects men and women throughout the world. It is influenced by non- controllable factors such as age, genetics and inflammatory colon diseases history (as is the case for ulcerative colitis) and by environmental factors such as dietary habits and physical activity. Often, the process of development and progression of this cancer goes through genetic alterations which affect the cellular proliferation, survival, migration and invasion mechanisms or through post- translational modifications such as the modification of the protein glycosylation. The aim of the study in question was to continue previously developed works, which demonstrated that a purified Arbutus unedo lectin demonstrated, in vitro, antitumoural activity. In this project, the anti- inflammatory action of this A.unedo lectin was studied in a in vivo model (model of colitis in mice). The results of the in vivo trials demonstrated that the lectin mitigates the effects of colitis predicting, for that reason, its link to the glycosylated receptors of the altered colon’s cells. The lectins display specificity for these anomalous receptors and revert the injury, probably through a mechanism of altered cell death mechanisms. Associated to the fact that the trials with lectin in mice without colitis did not reveal any alterations to the colon shows that the lectin did not reveal specificities to these receptors in cells of healthy colons, seen as this tissue did not reveal any injury. Thus, we conclude that this lectin is probably specific to receptors of inflamed tissue.
Lectins are a wide/broad group of proteins which can specifically link themselves to glycosylated receptors. These proteins are present throughout nature and possess biochemical characteristics which make them unique in terms of cellular recognition. They are excellent differentiators of cells in which alterations in terms of these glycosylated receptors can be found. That is to say that these proteins recognise cells with glycomic aberrations which are characteristic of the most varied pathological processes, especially tumoural ones. Their biochemical characteristics and their capacity to decode glycocodes, lectins have been targeted to intense biomedical research, with great investment in their biotechnological capacities, aiming at their therapeutic applications. Colorectal cancer is the second most prevailing cancer in Portugal, and the third one which most affects men and women throughout the world. It is influenced by non- controllable factors such as age, genetics and inflammatory colon diseases history (as is the case for ulcerative colitis) and by environmental factors such as dietary habits and physical activity. Often, the process of development and progression of this cancer goes through genetic alterations which affect the cellular proliferation, survival, migration and invasion mechanisms or through post- translational modifications such as the modification of the protein glycosylation. The aim of the study in question was to continue previously developed works, which demonstrated that a purified Arbutus unedo lectin demonstrated, in vitro, antitumoural activity. In this project, the anti- inflammatory action of this A.unedo lectin was studied in a in vivo model (model of colitis in mice). The results of the in vivo trials demonstrated that the lectin mitigates the effects of colitis predicting, for that reason, its link to the glycosylated receptors of the altered colon’s cells. The lectins display specificity for these anomalous receptors and revert the injury, probably through a mechanism of altered cell death mechanisms. Associated to the fact that the trials with lectin in mice without colitis did not reveal any alterations to the colon shows that the lectin did not reveal specificities to these receptors in cells of healthy colons, seen as this tissue did not reveal any injury. Thus, we conclude that this lectin is probably specific to receptors of inflamed tissue.
Descrição
Tese de mestrado, Controlo de Qualidade e Toxicologia dos Alimentos, Universidade de Lisboa, Faculdade de Farmácia, 2017
Palavras-chave
Lectina carcinoma colorretal aberração glicómia colite ulcerosa inflamação Teses de mestrado - 2017