Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico

Detalhes bibliográficos
Ano de defesa: 2025
Autor(a) principal: Almeida, Marina Gabrielle Guimarães de
Orientador(a): Ramos, Márcio Viana
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/80192
Resumo: Calotropis procera is a laticifer plant from the Apocynaceae family, native to India, widely used in traditional medicine, where several pharmacological properties of the latex solubleproteins (LP) of this species are being reported, such as anti-inflammatory, analgesic, antitumor, anticancer, anti-hyperglycemic and antioxidant activities, among others. Recently LP was used in the development of a rennet for cheese production, and in the development of a polyvinyl alcohol (PVA)-based biomembrane for wound healing, tested in an animal model. Despite the studies conducted regarding the potential for application of LP as phytotherapeutic and the already reported safety of these proteins, the present study aims to improve the evaluation of the toxicological and allergenic properties, as well as to present a better understanding of the safety of use of biotechnological inputs produced from C. procera LP. To this end, oral toxicity tests were performed in Swiss mice for 28 days on 3 different doses of LP (1000, 500 and 250 mg/mL), then biochemical, histological, and hematological parameters were analyzed for changes that could indicate toxicity. To analyze the stability of LP, in vitro digestibility assays were executed in simulated gastric and intestinal fluids in sequential and non-sequential manner. To investigate the allergenicity of latex proteins, a patch test was performed in humans with PVA-based biomembranes (BioMem CpLP). At the three doses tested for toxicity, no change was seen within the parameters analyzed that could indicate LP as an orally toxic substance. In the allergenicity test, 52 volunteers participated in the study, where 12% of the volunteers had a mild allergic reaction in the first phase and 5% of the volunteers who completed the first phase had mild allergic reaction, showing that PL is safe for therapeutic use. This study suggests that C. procera latex proteins are safe for use for their therapeutic potential in these conditions.
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spelling Almeida, Marina Gabrielle Guimarães deRamos, Márcio Viana2025-03-27T11:15:36Z2025-03-27T11:15:36Z2025ALMEIDA, Marina Gabrielle Guimarães de. Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico. 2025. 91 f. Tese (Doutorado em Bioquímica) - Programa de Pós-Graduação em Bioquímica, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2025.http://repositorio.ufc.br/handle/riufc/80192Calotropis procera is a laticifer plant from the Apocynaceae family, native to India, widely used in traditional medicine, where several pharmacological properties of the latex solubleproteins (LP) of this species are being reported, such as anti-inflammatory, analgesic, antitumor, anticancer, anti-hyperglycemic and antioxidant activities, among others. Recently LP was used in the development of a rennet for cheese production, and in the development of a polyvinyl alcohol (PVA)-based biomembrane for wound healing, tested in an animal model. Despite the studies conducted regarding the potential for application of LP as phytotherapeutic and the already reported safety of these proteins, the present study aims to improve the evaluation of the toxicological and allergenic properties, as well as to present a better understanding of the safety of use of biotechnological inputs produced from C. procera LP. To this end, oral toxicity tests were performed in Swiss mice for 28 days on 3 different doses of LP (1000, 500 and 250 mg/mL), then biochemical, histological, and hematological parameters were analyzed for changes that could indicate toxicity. To analyze the stability of LP, in vitro digestibility assays were executed in simulated gastric and intestinal fluids in sequential and non-sequential manner. To investigate the allergenicity of latex proteins, a patch test was performed in humans with PVA-based biomembranes (BioMem CpLP). At the three doses tested for toxicity, no change was seen within the parameters analyzed that could indicate LP as an orally toxic substance. In the allergenicity test, 52 volunteers participated in the study, where 12% of the volunteers had a mild allergic reaction in the first phase and 5% of the volunteers who completed the first phase had mild allergic reaction, showing that PL is safe for therapeutic use. This study suggests that C. procera latex proteins are safe for use for their therapeutic potential in these conditions.Calotropis procera é uma planta laticífera da família Apocynaceae, originária na Índia, muito utilizada na medicina tradicional.. Foram relatadas diversas propriedades farmacológicas das proteínas solúveis do látex (PL) desta espécie, como atividades anti-inflamatórias, analgésica, antitumoral, nticancer, anti-hiperglicêmica, antioxidante entre outros. Recentemente as PL foram utilizadas no desenvolvimento de um coalho para a produção de queijo, e no desenvolvimento de uma biomembrana à base de álcool polivinílico (PVA), para cicatrização de feridas testadas em modelo animal. Apesar dos estudos realizados a respeito do potencial para aplicação de PL como fitoterápico e da segurança já relatada destas proteínas, o presente estudo tem como objetivo aprimorar a avaliação das propriedades toxicológicas e alergênicas, bem como ter bom entendimento da segurança de uso de insumos produzidos a partir de PL de C. procera. Para isso, foram realizados testes de toxicidade oral em camundongos Swiss por 28 dias em 3 doses distintas de PL (1000, 500 e 250 mg/mL), em seguida foram analisados parâmetros bioquímicos, histológicos e hematológicos em busca de alterações que pudessem indicar toxicidade. Foram realizados ensaios in vitro para verificar a estabilidade de PL no trato digestivo utilizando fluidos simulados de forma não sequencial e sequencial. Para investigar a alergenicidade das proteínas do látex, foi realizado um teste de contato (patch test) em humanos com biomembranas a base de PVA (BioMem CpLP). Nas três doses testadas para toxicidade, não foi documentada, dentro dos parâmetros analisados, qualquer mudança que pudesse ter sido provocada por PL como uma substância tóxica, por via oral. Nos testes de digestibilidade in vitro PL se manteve estável durante a digestão não sequencial e sequencial, além de permanecer com a sua atividade proteolítica estável durante o processo. No teste de alergenicidade, 52 voluntários humanos participaram do estudo, onde 12% destes apresentaram discreta reação alérgica na primeira fase e 5% dos voluntários que concluíram a segunda fase apresentaram reação alérgica leve, sugerindo que PL são seriam seguras para uso terapêutico. O estudo sugere que as proteínas do látex de C. procera são seguros para uso de seu potencial terapêutico nessas condições.Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêuticoRisk assessment (toxicity/allergenicity) of Calotropis procera latex proteins as therapeutic inputinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisAlergiaBiomembranaDigestibilidadeHistopatologiaTeste de contatoBiomembraneDigestibilityHistopathologyPatchTestCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFC2025-03-27LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/80192/4/license.txt8a4605be74aa9ea9d79846c1fba20a33MD54ORIGINAL2025_tese_mggalmeida.pdf2025_tese_mggalmeida.pdfapplication/pdf1786225http://repositorio.ufc.br/bitstream/riufc/80192/3/2025_tese_mggalmeida.pdfd6b6c37c8415fb054cbf03063b72af09MD53riufc/801922025-03-27 12:21:34.848oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2025-03-27T15:21:34Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico
dc.title.en.pt_BR.fl_str_mv Risk assessment (toxicity/allergenicity) of Calotropis procera latex proteins as therapeutic input
title Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico
spellingShingle Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico
Almeida, Marina Gabrielle Guimarães de
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
Alergia
Biomembrana
Digestibilidade
Histopatologia
Teste de contato
Biomembrane
Digestibility
Histopathology
Patch
Test
title_short Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico
title_full Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico
title_fullStr Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico
title_full_unstemmed Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico
title_sort Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico
author Almeida, Marina Gabrielle Guimarães de
author_facet Almeida, Marina Gabrielle Guimarães de
author_role author
dc.contributor.author.fl_str_mv Almeida, Marina Gabrielle Guimarães de
dc.contributor.advisor1.fl_str_mv Ramos, Márcio Viana
contributor_str_mv Ramos, Márcio Viana
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
topic CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
Alergia
Biomembrana
Digestibilidade
Histopatologia
Teste de contato
Biomembrane
Digestibility
Histopathology
Patch
Test
dc.subject.ptbr.pt_BR.fl_str_mv Alergia
Biomembrana
Digestibilidade
Histopatologia
Teste de contato
dc.subject.en.pt_BR.fl_str_mv Biomembrane
Digestibility
Histopathology
Patch
Test
description Calotropis procera is a laticifer plant from the Apocynaceae family, native to India, widely used in traditional medicine, where several pharmacological properties of the latex solubleproteins (LP) of this species are being reported, such as anti-inflammatory, analgesic, antitumor, anticancer, anti-hyperglycemic and antioxidant activities, among others. Recently LP was used in the development of a rennet for cheese production, and in the development of a polyvinyl alcohol (PVA)-based biomembrane for wound healing, tested in an animal model. Despite the studies conducted regarding the potential for application of LP as phytotherapeutic and the already reported safety of these proteins, the present study aims to improve the evaluation of the toxicological and allergenic properties, as well as to present a better understanding of the safety of use of biotechnological inputs produced from C. procera LP. To this end, oral toxicity tests were performed in Swiss mice for 28 days on 3 different doses of LP (1000, 500 and 250 mg/mL), then biochemical, histological, and hematological parameters were analyzed for changes that could indicate toxicity. To analyze the stability of LP, in vitro digestibility assays were executed in simulated gastric and intestinal fluids in sequential and non-sequential manner. To investigate the allergenicity of latex proteins, a patch test was performed in humans with PVA-based biomembranes (BioMem CpLP). At the three doses tested for toxicity, no change was seen within the parameters analyzed that could indicate LP as an orally toxic substance. In the allergenicity test, 52 volunteers participated in the study, where 12% of the volunteers had a mild allergic reaction in the first phase and 5% of the volunteers who completed the first phase had mild allergic reaction, showing that PL is safe for therapeutic use. This study suggests that C. procera latex proteins are safe for use for their therapeutic potential in these conditions.
publishDate 2025
dc.date.accessioned.fl_str_mv 2025-03-27T11:15:36Z
dc.date.available.fl_str_mv 2025-03-27T11:15:36Z
dc.date.issued.fl_str_mv 2025
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv ALMEIDA, Marina Gabrielle Guimarães de. Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico. 2025. 91 f. Tese (Doutorado em Bioquímica) - Programa de Pós-Graduação em Bioquímica, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2025.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/80192
identifier_str_mv ALMEIDA, Marina Gabrielle Guimarães de. Determinação de risco (toxicidade/alergenicidade) de proteínas do látex de Calotropis procera como insumo terapêutico. 2025. 91 f. Tese (Doutorado em Bioquímica) - Programa de Pós-Graduação em Bioquímica, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2025.
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