Associação do polimorfismo MnSOD ALA16VAL com os biomarcadores inflamatórios, apoptóticos e BDNF em pacientes após acidente vascular encefálico tardio

• Ano de defesa: 2017
• Autor(a) principal: Flores, Ariane Ethur
• Orientador(a): Fighera, Michele Rechia
• Banca de defesa: Cabrini, Daniela de Almeida , Santos, Gabriela Trevisan dos , Ferreira, Juliano
• 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 Farmacologia
• Departamento: Farmacologia
• País: Brasil
• Palavras-chave em Português: Polimorfismo; Estresse oxidativo; Citocinas inflamatórias; Caspase; Dano ao DNA; Dislipidemia
• Palavras-chave em Inglês: Polimorphysm; Oxidative stress; Inflammatory cytokines; Caspase; DNA damage; Hypercholesterolemia
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
• Link de acesso: http://repositorio.ufsm.br/handle/1/17963

Stroke is one of the most frequent neurologic diseases and involves various risk factors such as atherosclerosis, dyslipidemia and diabetes mellitus. Furthermore, the mechanisms of action associated with the pathophysiology of stroke involve multiple interaction pathways such as inflammation, oxidative stress, apoptosis, genetic factors and modulation of neurotrophic factors such as brain-derived neurotrophic factor (BDNF). Studies has showed that genetics mutation as MnSOD Ala16Val single nucleotide polymorphism (SNP) to be associated to risk factors of vascular diseases, as well as with modulation of inflammation and oxidative pathways. However, little is known about the relationship between MnSOD Ala16Val SNP with stroke and plasmatic BDNF levels and also its influence on inflammatory, oxidative stress, apoptosis and glycolipid parameters on stroke. For this purpose, stroke patients and healthy subjects were recruited to biochemistry analysis. We analyzed glycolipid profile, IL-1, IL-6, IFN-γ and BDNF levels, as well as caspases (1 and 3) activation, oxidative stress, apoptosis, DNA damage and spasticity of stroke patients comparated whith healthy subjects. Results showed a higher proportion of VV genotype in post-stroke as compared to healthy subjects. The results also indicated that stroke patients had higher cholesterol (CHO) and glucose (GLU) levels when compared to healthy counterparts. Interestingly, V allele carriers with stroke showed higher levels of CHO and GLU levels when compared to AA stroke and healthy counterparts. Furthermore, results show that oxidative stress parameters (TBARS, levels of nitrite and nitrate (NOx), SOD and catalase activities) and DNA damage are increased in stroke group compared to healthy individuals, even after 6 months of stroke. The values of total cholesterol, LDL, IL-1, IL- 6, and INF- levels also were higher in VV post-stroke as compared to AA, AV post-stroke and control group. The triglycerides and glucose levels and caspases (1 and 3) activation were significantly higher in VV and AV post-stroke patients as compared to AA post-stroke and control group. The BDNF levels were lower in VV and AV post-stroke patients as compared to AA post-stroke and control group. The DNA damage was higher in stroke group when compared to control group. The results also showed a correlation between IL-1 and spasticity in VV post-stroke as compared to others groups. Our results suggest that polymorphism in MnSOD Ala16Val may contribute to hypercholesterolemia and higher levels of GLU, leading to alteration in neurovascular homeostasis. These events contribute to an increase in inflammatory markers, oxidative, apoptotic and in reducing BDNF, contributing to the pathophysiology of neurovascular disease.