Potencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivo
Ano de defesa: | 2023 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências da Saúde |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Farmacêuticas
|
Departamento: |
Farmácia
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/30451 |
Resumo: | Iron (Fe) and glucose (GLU) are essential elements for most forms of life. However, the progressive increase inevitably leads to pathological conditions, such as Fe overload and diabetes disease. Drug therapy consists in the use of binders and antidiabetics, however, the drugs available have numerous restrictions on use and adverse effects, making the therapy unsatisfactory. Due to the existing difficulties, the need for further research is essential. Recent studies demonstrate that Phenolic Compounds are important in this search. Among Them, there are caffeic acid (CA) and ferulic acid (FA), known for their antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, antitumor, hepatoprotective, nephroprotective and neuroprotective activity already described. Therefore, the objective was to evaluate behavior of the compounds in silico and in vivo. For this, the in silico toxic risk assessment was performed using the pkCSM, lazar, OSIRIS, ProTox-II and admetSAR tools, and pharmacophoric models of CA and FA wereals developed against the proteins of GLU and Fe metabolism via molecular docking. The results obtained the in silico prediction did not show significant toxicological effects. Subsequently, two in vivo studies with Wistar rats were developed. In the first study, the induced groups received Fe dextran and treated groups CA, FA and CA+FA (10 mg/kg/day), while the control group received desferrioxamine (DFO). Biochemical and hematological parameters and tissue oxidative stress markers were analyzed. The experimental model showed increased levels serum Fe and changes in several parameters such as GLU, liver markers and heart damage. CA demonstrated better control of the effects from Fe overload and the association acid did not demonstrate synergism. Docking showed that carbonic anhydrase interacted with the test molecules and CA showed less energy expenditure in this interaction. In the second study, to induce diabetes, the animals received streptozotocin (STZ) (55 mg/kg), treated groups received CA and FA and CA+FA at a dose of 10 mg/kg/day, and control group received an equivalent volume of filtered water or metformin (100 mg/kg). Treated animals showed improvement in blood glucose and biochemical markers when compared to untreated animals. Dockings howed that α-glucosidase inhibition possibly the cause of improvement in diabetic disease. In these results, there are indications that CA and FA may have therapeutic potential in the treatment diseases, like diabetic disease and Fe overload. |
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2023-11-09T13:19:20Z2023-11-09T13:19:20Z2023-08-18http://repositorio.ufsm.br/handle/1/30451Iron (Fe) and glucose (GLU) are essential elements for most forms of life. However, the progressive increase inevitably leads to pathological conditions, such as Fe overload and diabetes disease. Drug therapy consists in the use of binders and antidiabetics, however, the drugs available have numerous restrictions on use and adverse effects, making the therapy unsatisfactory. Due to the existing difficulties, the need for further research is essential. Recent studies demonstrate that Phenolic Compounds are important in this search. Among Them, there are caffeic acid (CA) and ferulic acid (FA), known for their antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, antitumor, hepatoprotective, nephroprotective and neuroprotective activity already described. Therefore, the objective was to evaluate behavior of the compounds in silico and in vivo. For this, the in silico toxic risk assessment was performed using the pkCSM, lazar, OSIRIS, ProTox-II and admetSAR tools, and pharmacophoric models of CA and FA wereals developed against the proteins of GLU and Fe metabolism via molecular docking. The results obtained the in silico prediction did not show significant toxicological effects. Subsequently, two in vivo studies with Wistar rats were developed. In the first study, the induced groups received Fe dextran and treated groups CA, FA and CA+FA (10 mg/kg/day), while the control group received desferrioxamine (DFO). Biochemical and hematological parameters and tissue oxidative stress markers were analyzed. The experimental model showed increased levels serum Fe and changes in several parameters such as GLU, liver markers and heart damage. CA demonstrated better control of the effects from Fe overload and the association acid did not demonstrate synergism. Docking showed that carbonic anhydrase interacted with the test molecules and CA showed less energy expenditure in this interaction. In the second study, to induce diabetes, the animals received streptozotocin (STZ) (55 mg/kg), treated groups received CA and FA and CA+FA at a dose of 10 mg/kg/day, and control group received an equivalent volume of filtered water or metformin (100 mg/kg). Treated animals showed improvement in blood glucose and biochemical markers when compared to untreated animals. Dockings howed that α-glucosidase inhibition possibly the cause of improvement in diabetic disease. In these results, there are indications that CA and FA may have therapeutic potential in the treatment diseases, like diabetic disease and Fe overload.O ferro (Fe) e a glicose (GLI) são elementos primordiais para a maioria das formas de vida. Porém, o aumento progressivo leva, inevitavelmente, a condições patológicas como a sobrecarga de Fe e a doença diabética. A terapia medicamentosa consiste na utilização de quelantes e antidiabéticos, todavia, os fármacos disponíveis possuem inúmeras restrições de uso e efeitos adversos, tornando a terapia insatisfatória. Devido às dificuldades estabelecidas, viu-se a necessidade de novas pesquisas. Estudos recentes demonstram que compostos fenólicos estão em destaque nesta busca. Dentre estes, encontram-se o ácido cafeico (CA) e ácido ferúlico (FA), conhecidos pela sua atividade antioxidante, antiinflamatória, antimicrobiana, imunomodulatória, antitumoral, hepatoprotetora, nefroprotetora e neuroprotetora já descritas na literatura. Assim, objetivou-se avaliar o comportamento dos compostos CA e FA in silico e in vivo. Para isso, a avaliação de risco toxicológico in silico foi realizada através das ferramentas pkCSM, lazar, OSIRIS, ProTox-II e admetSAR, e também foram desenvolvidos modelos farmacofóricos do CA e FA frente as proteínas envolvidas no metabolismo do GLI e do Fe via docking molecular. Os resultados obtidos na predição in silico não demonstraram efeitos toxicológicos significativos. Posteriormente, foram desenvolvidos dois estudos in vivo com ratos Wistar. No primeiro estudo, os grupos induzidos receberam Fe dextran e os grupos tratados CA, FA e CA+FA (10 mg/kg/dia) e o grupo droga padrão recebeu desferroxamina (DFO). Foram analisados parâmetros bioquímicos, hematológicos e marcadores de estresse oxidativo. O modelo experimental mostrou níveis aumentados de Fe sérico e alterações em vários parâmetros como GLI, marcadores de dano hepático e cardíaco. O CA demonstrou controlar melhor os efeitos da sobrecarga de Fe e a associação de ácidos não demonstrou sinergismo. O docking mostrou que a anidrase carbônica interagiu com as moléculas teste e o CA apresentou menor gasto de energia nessa interação. No segundo estudo, para induzir diabetes, os animais receberam estreptozotocina (STZ) (55 mg/kg), grupos tratados receberam CA e FA e CA+FA na dose de 10 mg/kg/dia, e os grupos controle receberam volume equivalente de água filtrada ou metformina (100 mg/kg). Os animais tratados apresentaram melhora na glicemia e nos marcadores bioquímicos quando comparados aos animais não tratados. O docking mostrou que a inibição da αglicosidase é possivelmente a causa da melhora na doença diabética. Com base nesses resultados, há indicações de que o CA e FA podem ter potencial terapêutico no tratamento de doenças, como a doença diabética e sobrecarga de Fe.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilFarmáciaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessDiabetesHemocromatoseÁcidos fenólicosDockingHemochromatosisPhenolic acidsCNPQ::CIENCIAS DA SAUDE::FARMACIAPotencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivoPharmacological potential of caffeic and ferulic acids in iron overload and diabetic disease: in silico and in vivo approachinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisBauermann, Liliane de Freitashttp://lattes.cnpq.br/5849925846135968Branco, Cátia dos SantosSantos, Gabriela Trevisan dosMansur, Michel MachadoBrucker, Natáliahttp://lattes.cnpq.br/6438220489230243Figueredo, Kássia Caroline400300000005600600600600600600600948e5e71-a7c8-46ad-983f-f52ac6f2ac214b6b87f4-8392-4c81-a348-e465873d22a86183766f-2864-437d-aa0c-d0c198fda51208e5dbeb-aeac-40a4-954a-a0753609d005a9949bb8-1542-4839-bbdc-ea9f2f8ec54ee2423ca5-c34e-47af-98a6-ba143d378dfareponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Potencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivo |
dc.title.alternative.eng.fl_str_mv |
Pharmacological potential of caffeic and ferulic acids in iron overload and diabetic disease: in silico and in vivo approach |
title |
Potencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivo |
spellingShingle |
Potencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivo Figueredo, Kássia Caroline Diabetes Hemocromatose Ácidos fenólicos Docking Hemochromatosis Phenolic acids CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Potencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivo |
title_full |
Potencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivo |
title_fullStr |
Potencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivo |
title_full_unstemmed |
Potencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivo |
title_sort |
Potencial farmacológico dos ácidos cafeico e ferúlico na sobrecarga de ferro e na doença diabética: abordagem in silico e in vivo |
author |
Figueredo, Kássia Caroline |
author_facet |
Figueredo, Kássia Caroline |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bauermann, Liliane de Freitas |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5849925846135968 |
dc.contributor.referee1.fl_str_mv |
Branco, Cátia dos Santos |
dc.contributor.referee2.fl_str_mv |
Santos, Gabriela Trevisan dos |
dc.contributor.referee3.fl_str_mv |
Mansur, Michel Machado |
dc.contributor.referee4.fl_str_mv |
Brucker, Natália |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/6438220489230243 |
dc.contributor.author.fl_str_mv |
Figueredo, Kássia Caroline |
contributor_str_mv |
Bauermann, Liliane de Freitas Branco, Cátia dos Santos Santos, Gabriela Trevisan dos Mansur, Michel Machado Brucker, Natália |
dc.subject.por.fl_str_mv |
Diabetes Hemocromatose Ácidos fenólicos Docking |
topic |
Diabetes Hemocromatose Ácidos fenólicos Docking Hemochromatosis Phenolic acids CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Hemochromatosis Phenolic acids |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Iron (Fe) and glucose (GLU) are essential elements for most forms of life. However, the progressive increase inevitably leads to pathological conditions, such as Fe overload and diabetes disease. Drug therapy consists in the use of binders and antidiabetics, however, the drugs available have numerous restrictions on use and adverse effects, making the therapy unsatisfactory. Due to the existing difficulties, the need for further research is essential. Recent studies demonstrate that Phenolic Compounds are important in this search. Among Them, there are caffeic acid (CA) and ferulic acid (FA), known for their antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, antitumor, hepatoprotective, nephroprotective and neuroprotective activity already described. Therefore, the objective was to evaluate behavior of the compounds in silico and in vivo. For this, the in silico toxic risk assessment was performed using the pkCSM, lazar, OSIRIS, ProTox-II and admetSAR tools, and pharmacophoric models of CA and FA wereals developed against the proteins of GLU and Fe metabolism via molecular docking. The results obtained the in silico prediction did not show significant toxicological effects. Subsequently, two in vivo studies with Wistar rats were developed. In the first study, the induced groups received Fe dextran and treated groups CA, FA and CA+FA (10 mg/kg/day), while the control group received desferrioxamine (DFO). Biochemical and hematological parameters and tissue oxidative stress markers were analyzed. The experimental model showed increased levels serum Fe and changes in several parameters such as GLU, liver markers and heart damage. CA demonstrated better control of the effects from Fe overload and the association acid did not demonstrate synergism. Docking showed that carbonic anhydrase interacted with the test molecules and CA showed less energy expenditure in this interaction. In the second study, to induce diabetes, the animals received streptozotocin (STZ) (55 mg/kg), treated groups received CA and FA and CA+FA at a dose of 10 mg/kg/day, and control group received an equivalent volume of filtered water or metformin (100 mg/kg). Treated animals showed improvement in blood glucose and biochemical markers when compared to untreated animals. Dockings howed that α-glucosidase inhibition possibly the cause of improvement in diabetic disease. In these results, there are indications that CA and FA may have therapeutic potential in the treatment diseases, like diabetic disease and Fe overload. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-11-09T13:19:20Z |
dc.date.available.fl_str_mv |
2023-11-09T13:19:20Z |
dc.date.issued.fl_str_mv |
2023-08-18 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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http://repositorio.ufsm.br/handle/1/30451 |
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http://repositorio.ufsm.br/handle/1/30451 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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400300000005 |
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600 600 600 600 600 600 600 |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Farmacêuticas |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmácia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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