Efeitos da terapia imunossupressora na estrutura e função do trato gastrintestinal de ratos
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Data
2018-03-06
Autores
Dall'Agnol, Denize Jussara Rupolo
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Os imunossupressores são utilizados após o transplante de órgãos e no tratamento de doenças autoimunes, desencadeando diversos efeitos colaterais. No esquema tríplice de imunossupressão pós-transplante, cada droga ou a combinação delas podem alterar a estrutura e/ou funcionamento do trato gastrintestinal. Apesar da importância do trato gastrintestinal e de conhecer os efeitos da ingesta oral de imunossupressores, há poucos estudos enfocando esses aspectos e vários desafios éticos para essas avaliações no homem. Desse modo, objetivou-se avaliar as alterações provocadas pela imunossupressão nos parâmetros de esvaziamento gástrico, frequência e amplitude das contrações gástricas, bem como as alterações histológicas no estômago de ratos. Para isso foram utilizados a Biosusceptometria de Corrente Alternada (BAC) e a Eletrogastrografia (EGG). No primeiro capítulo, avaliou-se individualmente sete imunossupressores de diferentes classes (Tacrolimo, Ciclosporina, Micofenolato Mofetil, Azatioprina, Sirolimo, Everolimo e Prednisona) comumente utilizados na terapia imunossupressora. Todos os imunossupressores estudados, exceto o Micofenolato Mofetil causaram alguma alteração nos parâmetros gastrintestinais analisados em ratos. Já o segundo capítulo apresenta os efeitos da terapia imunossupressora combinada, baseada em três classes de imunossupressores (inibidores da calcineurina, antimetabólitos e glicocorticoides). Um dos grupos experimentais recebeu Tacrolimo associado à Micofenolato Sódico e Prednisona, enquanto outro foi tratado com Ciclosporina associada à Azatioprina e Prednisona. Ambas as terapias alteraram o esvaziamento gástrico, a amplitude de contração gástrica e reduziram a espessura das camadas circular e longitudinal no estômago de ratos, embora a frequência tenha sido alterada apenas no grupo tratado com Ciclosporina associada à Azatioprina e Prednisona. Nossos dados apontaram que a monoterapia e a terapia combinada, alteram vários parâmetros da atividade motora ao mesmo tempo, podendo comprometer as funções básicas gastrintestinais.
Immunosuppressants are used after organ transplantation and in the treatment of autoimmune diseases, triggering several side effects. In the triple regimen of post - transplant immunosuppression, each drug or combination of them may alter the structure and / or function of the gastroin testinal tract. Despite the importance of gastrointestinal tract and knowledge of the effects of oral intake of immunosuppressants, there are few studies focusing on these aspects and several ethical challenges for these evaluations in humans. The aim of t his study was to evaluate the effects provoked by immunosuppression in gastric emptying parameters, frequency and amplitude of gastric contractions, as well as the histological aspects in the stomach of rats. Alternating Current Biosusceptometry (BAC) and Electrogastrography (EGG) were used. In the first chapter, seven immunosuppressants from different classes (Tacrolimus, Cyclosporine, Mycophenolate Mofetil, Azathioprine, Sirolimus, Everolimus and Prednisone) commonly used in immunosuppressive therapy were evaluated individually. All immunosuppressants studied except Mycophenolate Mofetil , caused some alteration in the gastrointestinal parameters analyzed in rats. The second chapter presents the effects of combined immunosuppressive therapy based on three c lasses of immunosuppressants (calcineurin inhibitors, antimetabolites and glucocorticoids). One of the experimental groups received Tacrolimus associated with Mycophenolate Sodium and Prednisone, while another was treated with Cyclosporine associated with Azathioprine and Prednisone. Both therapies altered gastric emptying, amplitude of gastric contraction, and reduced the thickness of the circular and longitudinal layers in the stomach of rats, although the frequency was disturbe d only in the Cyclosporine group associated with azathioprine and prednisone. Our data showed that monotherapy and combination therapy alter several parameters of motor activity at the same time, and may compromise basic gastrointestinal functions.
Immunosuppressants are used after organ transplantation and in the treatment of autoimmune diseases, triggering several side effects. In the triple regimen of post - transplant immunosuppression, each drug or combination of them may alter the structure and / or function of the gastroin testinal tract. Despite the importance of gastrointestinal tract and knowledge of the effects of oral intake of immunosuppressants, there are few studies focusing on these aspects and several ethical challenges for these evaluations in humans. The aim of t his study was to evaluate the effects provoked by immunosuppression in gastric emptying parameters, frequency and amplitude of gastric contractions, as well as the histological aspects in the stomach of rats. Alternating Current Biosusceptometry (BAC) and Electrogastrography (EGG) were used. In the first chapter, seven immunosuppressants from different classes (Tacrolimus, Cyclosporine, Mycophenolate Mofetil, Azathioprine, Sirolimus, Everolimus and Prednisone) commonly used in immunosuppressive therapy were evaluated individually. All immunosuppressants studied except Mycophenolate Mofetil , caused some alteration in the gastrointestinal parameters analyzed in rats. The second chapter presents the effects of combined immunosuppressive therapy based on three c lasses of immunosuppressants (calcineurin inhibitors, antimetabolites and glucocorticoids). One of the experimental groups received Tacrolimus associated with Mycophenolate Sodium and Prednisone, while another was treated with Cyclosporine associated with Azathioprine and Prednisone. Both therapies altered gastric emptying, amplitude of gastric contraction, and reduced the thickness of the circular and longitudinal layers in the stomach of rats, although the frequency was disturbe d only in the Cyclosporine group associated with azathioprine and prednisone. Our data showed that monotherapy and combination therapy alter several parameters of motor activity at the same time, and may compromise basic gastrointestinal functions.
Descrição
Palavras-chave
imunossupressores, motilidade gastrintestinal, biosusceptometria de corrente alternada, eletrogastrografia, transplante de órgãos, immunosuppressants, gastrointestinal motility, alternating current biosusceptometry, electrogastrography, organ transplantation