Avaliação do estresse oxidativo no órgão subfornical e no bulbo ventrolateral rostral de animais Knockout para apolipoproteína E

• Ano de defesa: 2017
• Autor(a) principal: Assis, Taísa França de Medeiros
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal da Paraíba; Brasil; Ciências Fisiológicas; Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas; UFPB
• Palavras-chave em Português: Estresse oxidativo; Aterosclerose; Citocinas inflamatórias; Oxidative stress; Atherosclerosis; Inflammatory cytokines; CIENCIAS BIOLOGICAS::FISIOLOGIA
• Link de acesso: https://repositorio.ufpb.br/jspui/handle/tede/9698

Atherosclerosis is a multifactorial disease, considered as one of the main risk factors that lead to the development of cardiovascular diseases. It is characterized by endothelial and autonomic dysfunction due to the presence of inflammation and systemic oxidative stress. The objective of this study was to evaluate the presence of ROS (reactive oxygen species) in the subfornical organ (SFO) and rostral ventrolateral medulla (RVLM) of animals knockout apolipoprotein E (apoE-/-) fed with a standard diet and the possible relation of the presence of peripheral inflammatory cytokines with central oxidative stress. So, for this purpose, the serum was collected from C57BL/6 mice, isogenic mice, and apoE-/-, mice, also isogenic, genetically modified for the deletion of the gene coding for apolipoprotein E. The serum was used for cholesterol dosage, lipid peroxidation in the form of malonialdehyde (MDA) and inflammatory cytokines (IL-1β, TNF-α and IL-10). In addition, the aortas of both groups were collected for the evaluation of lipid deposition. For the determination of reactive oxygen species by the dihydroethidine technique (DHE) and quantification of inflammatory cytokines (IL-1β, TNF-α and IL-10) were also collected samples from the SFO and RVLM from the two groups. We observed a significant increase in total cholesterol levels in apoE-/- animals compared to control animals (237.4±17.7 mg/dL n=6 vs 90.7±6.4 mg/dL n=6, p<0.05), both fed a standard diet. We also observed a higher lipid deposition in the apoE-/- animals when compared to controls (27.7±4.8% n=3 vs 5.3±0.6% n=4, p<0.05, respectively). There was an increase in serum levels of malonialdehyde in the apoE-/- mice compared to the control (1.8±0.2 nmol/mL, n=15 vs 1.1±0.2 nmol/mL, n=12, p<0.05). Regarding systemic inflammatory evaluation, we observed an increase in IL-1β levels in apoE-/- animals when compared to controls (17.7±2.9 pg/mL, n=11 vs 5.8±0.5 pg/ML, n=11, p<0.05), as well as TNF-α, which was also elevated in atherosclerotic animals (4.6±0.8 pg/mL, n=8 vs 2.1±0.6 pg/mL, n=8, p<0.05). However, we did not observe a significant difference in IL-10 levels when we compared the groups (apoE-/-: 201.6±16.0 pg/mL, n=6 vs C57BL/6: 190.1±11.1pg/mL, n=6). Regarding the evaluation of the oxidative stress in SFO and RVLM, an increase in O2•- levels was observed in both areas from the apoE-/- animals compared to the control (SFO: 36.4±2.1FR/u.a, n=4 vs 19.4±2 FR/u.a, 1, n=4, p<0.05; RVLM: 31.7±2.7 FR/u.a, n=4 vs 16.0±1.0 FR/u.a, n=5, p<0.05). Finally, we evaluated the levels of inflammatory cytokines in the SFO, and observed a decrease in the levels of both the proinflammatory cytokines (TNF-α and IL-1β) and IL-10 (anti-inflammatory) in apoE-/-: IL-1β (4.4±0.3 pg/mL n = 5, vs. 9.1 ± 0.8 pg/mL n=5, p<0.05), TNF-α (3.0±0.7 pg/mL, n=7 vs 6.4±0.9 pg/mL n=7, p<0.05), IL-10 (214.0±1.9 pg/mL n=3, vs 354.2±19.3 pg/mL n=3, p<0.05). Therefore, we can conclude that apoE-/- animals fed standard diet have high levels of ROS in the SFO and RVLM, which together are important regions responsible for cardiovascular control. We may also suggest that the peripheral inflammatory cytokines participate in the induction of central oxidative stress from its action in the SFO.