Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6

Detalhes bibliográficos
Ano de defesa: 2025
Autor(a) principal: Carvalho, Kalleu Fernando de Alencar
Orientador(a): Sousa, Francisca Cléa Florenço de
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
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/80095
Resumo: Dyslipidemia is characterized as a disorder whose prevalence has been progressively increasing in Brazil and worldwide, and is essential from a public health perspective. The disease can be defined by lipid metabolic alterations that affect the bloodstream, characterized by an increase in total cholesterol, triglycerides, low-density lipoprotein (LDL) and a decrease in high-density lipoprotein (HDL). These alterations are associated with cardiovascular risks and atherosclerosis, which can result in serious cardiovascular events. In view of this, new pharmacological treatments have been based on the investigation of substances of natural origin, such as polyphenols found in tyramine, a monoamine, available in plants, studied for their effects on lipid and carbohydrate metabolism. In this context, riparins (RIP), metabolites of tyramine, have bioactive activity and have been studied for their various biological effects, including anti-inflammatory, antioxidant, anxiolytic and antidepressant effects. The aim of this study was to investigate the lipid-lowering effect of Riparin I (RIP I) in the dyslipidemia model induced by poloxamer P407 in C57BL/6 mice. An acute toxicity study of RIP I was performed according to parameters established by OECD 423 to determine the doses used. Dyslipidemia was induced by a single intraperitoneal injection of P-407 at a dose of 400 mg/kg. The groups were treated four times, as follows: a pretreatment (2 h before administration of P-407), doses of RIP I at concentrations of 100, 50 and 25 mg/kg, followed by treatments 24 h, 48 h and 72 h after intraperitoneal administration of P-407. Two hours after the last treatment, the animals were anesthetized and submitted to blood collection for biochemical dosages of cholesterol, triglycerides and liver markers. At the end of the protocols, the liver was removed for measurement of the antioxidant parameters TBARS, GSH and catalase (U/mg of protein). Low toxicity of RIP I was identified in cardiac, hepatic, renal and brain tissues, being classified in category 5 according to the Globally Harmonized Classification OECD. RIP I was not able to reduce cholesterol and triglyceride levels in animals, however, it demonstrated antioxidant potential through the reduction of TBARS levels, as well as the increase in GSH/GSSG. Additionally, RIP I enabled an increase in HDL cholesterol levels compared to the P407 group. A significant increase in non-HDL cholesterol indices, in the HDLc/TC and TG/HDLc ratios was also identified. In the histological analyses of the dyslipidemia protocol, there were no macroscopic and histopathological changes in the liver tissue, with no changes in aminotransferases (AST and ALT). It is concluded that potential action of RIP I on HDLc and significant antioxidant effect in liver tissue were identified in this model; however, RIP I was unable to reduce triglyceride and total cholesterol levels induced by P407. In summary, future experiments studying riparin I in a chronic model of dyslipidemia induced by a high-fat diet are valid, in order to verify its action, without drug induction, through obesity in mice.
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spelling Carvalho, Kalleu Fernando de AlencarSousa, Francisca Cléa Florenço de2025-03-20T12:53:38Z2025-03-20T12:53:38Z2025CARVALHO, Kalleu Fernando de Alencar. Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6, 2025. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2025. Disponível em: http://repositorio.ufc.br/handle/riufc/80095. Acesso em: 20 mar. 2025.http://repositorio.ufc.br/handle/riufc/80095Dyslipidemia is characterized as a disorder whose prevalence has been progressively increasing in Brazil and worldwide, and is essential from a public health perspective. The disease can be defined by lipid metabolic alterations that affect the bloodstream, characterized by an increase in total cholesterol, triglycerides, low-density lipoprotein (LDL) and a decrease in high-density lipoprotein (HDL). These alterations are associated with cardiovascular risks and atherosclerosis, which can result in serious cardiovascular events. In view of this, new pharmacological treatments have been based on the investigation of substances of natural origin, such as polyphenols found in tyramine, a monoamine, available in plants, studied for their effects on lipid and carbohydrate metabolism. In this context, riparins (RIP), metabolites of tyramine, have bioactive activity and have been studied for their various biological effects, including anti-inflammatory, antioxidant, anxiolytic and antidepressant effects. The aim of this study was to investigate the lipid-lowering effect of Riparin I (RIP I) in the dyslipidemia model induced by poloxamer P407 in C57BL/6 mice. An acute toxicity study of RIP I was performed according to parameters established by OECD 423 to determine the doses used. Dyslipidemia was induced by a single intraperitoneal injection of P-407 at a dose of 400 mg/kg. The groups were treated four times, as follows: a pretreatment (2 h before administration of P-407), doses of RIP I at concentrations of 100, 50 and 25 mg/kg, followed by treatments 24 h, 48 h and 72 h after intraperitoneal administration of P-407. Two hours after the last treatment, the animals were anesthetized and submitted to blood collection for biochemical dosages of cholesterol, triglycerides and liver markers. At the end of the protocols, the liver was removed for measurement of the antioxidant parameters TBARS, GSH and catalase (U/mg of protein). Low toxicity of RIP I was identified in cardiac, hepatic, renal and brain tissues, being classified in category 5 according to the Globally Harmonized Classification OECD. RIP I was not able to reduce cholesterol and triglyceride levels in animals, however, it demonstrated antioxidant potential through the reduction of TBARS levels, as well as the increase in GSH/GSSG. Additionally, RIP I enabled an increase in HDL cholesterol levels compared to the P407 group. A significant increase in non-HDL cholesterol indices, in the HDLc/TC and TG/HDLc ratios was also identified. In the histological analyses of the dyslipidemia protocol, there were no macroscopic and histopathological changes in the liver tissue, with no changes in aminotransferases (AST and ALT). It is concluded that potential action of RIP I on HDLc and significant antioxidant effect in liver tissue were identified in this model; however, RIP I was unable to reduce triglyceride and total cholesterol levels induced by P407. In summary, future experiments studying riparin I in a chronic model of dyslipidemia induced by a high-fat diet are valid, in order to verify its action, without drug induction, through obesity in mice.A dislipidemia é caracterizada como um distúrbio cuja prevalência vem aumentando no Brasil e no mundo de forma progressiva, sendo fundamental do ponto de vista da saúde pública. A doença pode ser definida por alterações metabólicas lipídicas que afetam a corrente sanguínea, caracterizadas por aumento do colesterol total, triglicerídeos, lipoproteína de baixa densidade (LDL) e diminuição da lipoproteína de alta densidade (HDL). Essas alterações estão associadas a riscos cardiovasculares e à aterosclerose, que podem resultar em eventos cardiovasculares graves. Diante disso, novos tratamentos farmacológicos têm se baseado na investigação de substâncias de origem natural, como os polifenóis encontrados na tiramina, uma monoamina, disponíveis em plantas, estudada por seus efeitos no metabolismo de lipídeos e carboidratos. Nesse contexto, as riparinas (RIP), metabólitos da tiramina, apresentam atividade bioativa, e têm sido estudadas por seus diversos efeitos biológicos, incluindo anti-inflamatórias, antioxidantes, ansiolíticos e antidepressivos. O objetivo do presente estudo foi averiguar o efeito hipolipemiante da Riparina I (RIP I) no modelo de dislipidemia induzida por poloxamer P407 em camundongos C57BL/6. Foi realizado o estudo de toxicidade aguda da RIP I, de acordo com parâmetros estabelecidos pela OECD 423, para determinação das doses utilizadas. A dislipidemia foi induzida mediante única injeção via intraperitonial de P-407 na dose de 400mg/kg. Os grupos foram tratados quatro vezes, sendo: um pré-tratamento (2h antes da administração de P-407), doses de RIP I nas concentrações 100, 50 e 25mg/Kg, seguido de tratamentos 24h, 48h e 72h após a administração intraperitoneal de P-407. Duas horas após o último tratamento, os animais foram anestesiados e submetidos à coleta de sangue, para dosagens bioquímicas de colesterol, triglicerídeos e marcadores hepáticos. Ao fim dos protocolos, o fígado foi removido para dosagem dos parâmetros antioxidantes TBARS, GSH e catalase (U/mg de proteína). Foi identificada baixa toxicidade da RIP I nos tecidos cardíaco, hepático, renal e cerebral, sendo classificada na categoria 5 de acordo com o Globally Harmonized Classification OECD. A RIP I mostrou não ser capaz de reduzir as taxas de colesterol e triglicerídeos dos animais, entretanto, demonstrou um potencial antioxidante através da redução dos níveis de TBARS, bem como no aumento de GSH/GSSG. Adicionalmente, a RIP I possibilitou um aumento dos níveis de colesterol HDL comparado ao grupo P407. Também foi identificado um aumento significativo nos índices do Colesterol Não-HDL, na razão HDLc/CT e TG/HDLc. Nas análises histológicas do protocolo de dislipidemia, não houve alterações macroscópicas e histopatológicas no tecido hepático, sem alterações das aminotransferase (AST e ALT). Conclui-se que foi identificado potencial ação da RIP I no HDLc e efeito antioxidante significativo em tecido hepático neste modelo, contudo, a RIP I não conseguiu reduzir os níveis de triglicerídeos e colesterol total induzidos por P407. Em suma, é válido futuros experimentos que estudem a riparina I em modelo crônico de dislipidemia induzida por dieta hiperlipídica, a fim de verificar sua ação, sem a indução medicamentosa, por meio da obesidade em camundongos.Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6Lipid-lowering effect of Riparin I in a poloxamer 407-induced dyslipidemia model in C57BL/6 miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisToxicidadeHipolipemiantesAntioxidantesHypolipidemic AgentsAntioxidantsToxicityCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttps://orcid.org/0000-0001-9142-4498http://lattes.cnpq.br/5610035150959577https://orcid.org/0000-0002-9140-1795http://lattes.cnpq.br/1180465052181572ORIGINAL2025_dis_kfacarvalho.pdf2025_dis_kfacarvalho.pdfapplication/pdf1578181http://repositorio.ufc.br/bitstream/riufc/80095/1/2025_dis_kfacarvalho.pdf956ab99c09708ddeb9ed7784af02bb88MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/80095/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53riufc/800952025-03-20 09:58:04.764oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2025-03-20T12:58:04Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6
dc.title.en.pt_BR.fl_str_mv Lipid-lowering effect of Riparin I in a poloxamer 407-induced dyslipidemia model in C57BL/6 mice
title Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6
spellingShingle Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6
Carvalho, Kalleu Fernando de Alencar
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
Toxicidade
Hipolipemiantes
Antioxidantes
Hypolipidemic Agents
Antioxidants
Toxicity
title_short Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6
title_full Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6
title_fullStr Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6
title_full_unstemmed Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6
title_sort Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6
author Carvalho, Kalleu Fernando de Alencar
author_facet Carvalho, Kalleu Fernando de Alencar
author_role author
dc.contributor.author.fl_str_mv Carvalho, Kalleu Fernando de Alencar
dc.contributor.advisor1.fl_str_mv Sousa, Francisca Cléa Florenço de
contributor_str_mv Sousa, Francisca Cléa Florenço de
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
Toxicidade
Hipolipemiantes
Antioxidantes
Hypolipidemic Agents
Antioxidants
Toxicity
dc.subject.ptbr.pt_BR.fl_str_mv Toxicidade
Hipolipemiantes
Antioxidantes
dc.subject.en.pt_BR.fl_str_mv Hypolipidemic Agents
Antioxidants
Toxicity
description Dyslipidemia is characterized as a disorder whose prevalence has been progressively increasing in Brazil and worldwide, and is essential from a public health perspective. The disease can be defined by lipid metabolic alterations that affect the bloodstream, characterized by an increase in total cholesterol, triglycerides, low-density lipoprotein (LDL) and a decrease in high-density lipoprotein (HDL). These alterations are associated with cardiovascular risks and atherosclerosis, which can result in serious cardiovascular events. In view of this, new pharmacological treatments have been based on the investigation of substances of natural origin, such as polyphenols found in tyramine, a monoamine, available in plants, studied for their effects on lipid and carbohydrate metabolism. In this context, riparins (RIP), metabolites of tyramine, have bioactive activity and have been studied for their various biological effects, including anti-inflammatory, antioxidant, anxiolytic and antidepressant effects. The aim of this study was to investigate the lipid-lowering effect of Riparin I (RIP I) in the dyslipidemia model induced by poloxamer P407 in C57BL/6 mice. An acute toxicity study of RIP I was performed according to parameters established by OECD 423 to determine the doses used. Dyslipidemia was induced by a single intraperitoneal injection of P-407 at a dose of 400 mg/kg. The groups were treated four times, as follows: a pretreatment (2 h before administration of P-407), doses of RIP I at concentrations of 100, 50 and 25 mg/kg, followed by treatments 24 h, 48 h and 72 h after intraperitoneal administration of P-407. Two hours after the last treatment, the animals were anesthetized and submitted to blood collection for biochemical dosages of cholesterol, triglycerides and liver markers. At the end of the protocols, the liver was removed for measurement of the antioxidant parameters TBARS, GSH and catalase (U/mg of protein). Low toxicity of RIP I was identified in cardiac, hepatic, renal and brain tissues, being classified in category 5 according to the Globally Harmonized Classification OECD. RIP I was not able to reduce cholesterol and triglyceride levels in animals, however, it demonstrated antioxidant potential through the reduction of TBARS levels, as well as the increase in GSH/GSSG. Additionally, RIP I enabled an increase in HDL cholesterol levels compared to the P407 group. A significant increase in non-HDL cholesterol indices, in the HDLc/TC and TG/HDLc ratios was also identified. In the histological analyses of the dyslipidemia protocol, there were no macroscopic and histopathological changes in the liver tissue, with no changes in aminotransferases (AST and ALT). It is concluded that potential action of RIP I on HDLc and significant antioxidant effect in liver tissue were identified in this model; however, RIP I was unable to reduce triglyceride and total cholesterol levels induced by P407. In summary, future experiments studying riparin I in a chronic model of dyslipidemia induced by a high-fat diet are valid, in order to verify its action, without drug induction, through obesity in mice.
publishDate 2025
dc.date.accessioned.fl_str_mv 2025-03-20T12:53:38Z
dc.date.available.fl_str_mv 2025-03-20T12:53:38Z
dc.date.issued.fl_str_mv 2025
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dc.identifier.citation.fl_str_mv CARVALHO, Kalleu Fernando de Alencar. Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6, 2025. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2025. Disponível em: http://repositorio.ufc.br/handle/riufc/80095. Acesso em: 20 mar. 2025.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/80095
identifier_str_mv CARVALHO, Kalleu Fernando de Alencar. Efeito hipolipemiante da Riparina I em modelo de dislipidemia induzida por poloxamer 407 em camundongos C57BL/6, 2025. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2025. Disponível em: http://repositorio.ufc.br/handle/riufc/80095. Acesso em: 20 mar. 2025.
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