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Master's Dissertation
DOI
10.11606/D.9.2015.tde-29042015-102947
Document
Author
Full name
Jacqueline Cavalcante Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Abdalla, Dulcineia Saes Parra (President)
Martins, Joilson de Oliveira
Lima, Fabio Bessa
Title in Portuguese
Investigação dos efeitos de novos derivados tiazolidínicos em modelo animal de síndrome metabólica
Keywords in Portuguese
Diabetes mellitus (Tratamento)
Inflamação
Síndrome metabólica
Abstract in Portuguese
A síndrome metabólica (SM) é definida como um grupo de condições que aumentam o risco para doenças cardiovasculares e diabetes, com quadro clínico reconhecido por componentes como obesidade abdominal, dislipidemia, hipertensão arterial e resistência à insulina ou intolerância à glicose. Na população de 20 a 70 anos, apresenta prevalência de 24% no Brasil e no mundo. A resistência à insulina e a inflamação são demonstradas como características de grande importância na síndrome metabólica, que constituem alvos interessantes para novas abordagens terapêuticas. Nesse sentido, a classe de fármacos anti-diabéticos orais das tiazolidinadionas (TZDs), que são agonistas do receptor gama ativado por proliferadores de peroxissoma (PPAR=γ), cujo efeito hipoglicemiante é mediado pela redução da resistência à insulina sistêmica pelos tecidos periféricos, pode ser apontada como alternativa no tratamento de síndrome metabólica. No entanto, os fármacos dessa classe disponíveis comercialmente apresentam efeitos adversos importantes, o que incentivou a descoberta de novos derivados tiazolidínico, almejando a identificação de fármacos mais eficazes e com menos efeitos adversos. Considerando que os efeitos desses novos derivados tiazolidínicos ainda não haviam sido investigados em modelos de síndrome metabólica, o presente estudo objetivou avaliar os efeitos biológicos de quatro novos derivados tiazolidínicos, a saber, GQ-02, GQ-11, GQ-177 e Lyso-7 em modelo animal utilizando as linhagens de camundongo C57BL/6J e C57BL/6J LDLr -/-. O tratamento com os novos derivados tiazolidínicos mostrou efeito hipoglicemiante, com melhora na sensibilidade à insulina, no estado hiperinsulinêmico e hiperleptinêmico, além da modulação do perfil inflamatório e lipídico.
Title in English
Investigation of new thiazolidine compounds effects in animal model of metabolic syndrome
Keywords in English
Diabetes mellitus (Treatment)
Inflammation
Metabolic Syndrome
Abstract in English
Metabolic syndrome (MetS) can be defined as a group of conditions that increases cardiovascular diseases and diabetes risk, with obesity, dyslipidemia, arterial hypertension and insulin resistance or glucose intolerance as clinical features. The 20-70 years olds population have a prevalence of 24% in Brazil and world. An inflammatory reaction series and insulin resistance, also triggered by obesity, are demonstrated in metabolic syndrome what composes interesting targets to new therapeutic approaches. The anti-diabetic oral drugs class of thiazolidinediones (TZDs), that are peroxisome proliferator-activated receptor agonists, whose hypoglycemic effect is mediated by insulin resistance reduction in peripheral tissues, can be appointed how an alternative treatment of MetS. However, this class of drugs commercially available shows important adverse effects, such as weight increase and cardiovascular events risk. Thus, new thiazolidine compounds have been developed, craving identify more effective drugs and fewer adverse effects. Considering that these new thiazolidinediones effects aren't investigated in MetS models, the present study objects evaluated the action of four new thiazolidine compounds, denominated GQ-11, GQ-02, GQ-177 and Lyso-7 in animal model of MetS, using C57BL/6J and C57BL/6J LDLr -/- mice. The treatment with new thiazolidine compounds showed hypoglycemic effect, improving insulin resistance, hyperinsulinemia and hyperleptinemia, with peculiar characteristics on inflammatory and lipid profile modulation
 
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Publishing Date
2015-05-28
 
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