Caracterização da disfunção mitocondrial no rim de ratos Zucker

• Ano de defesa: 2016
• Autor(a) principal: Trindade, André Soares [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Mitochondria; Oxidative stress; Obesity; Kidney; Rats, Zucker; Mitocôndria; Estresse oxidativo; Obesidade; Rim; Ratos Zucker
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3775673; https://repositorio.unifesp.br/handle/11600/47305

Introduction: Obesity is characterized as an inflammatory condition associated to several chronic diseases. Besides promoting cardiovascular, hepatic and renal alterations, adipose tissue accumulation can generate an increased reninangiotensin-aldosterone system activity, increased oxidative stress and mitochondrial dysfunction. Aim: The aim of this study was to evaluate the kidney mitochondrial function of Zucker rats through cellular respiration, membrane potential, osmotic swelling, oxidative stress and antioxidant defense. Methods: Ten adult male rats were distributed into obese (Zucker rat strain with a mutation in the gene fa-/fa- and obese phenotype, N=5) and lean (lean Zucker rat strain, heterozygous fa+/fa- with eutrophic phenotype, N=5). In the kidney mitochondria we evaluated: the osmotic swelling with 3 different calcium concentrations (10, 25 or 50 µM Ca+2); the lipid peroxidation was measured by malondialdehyde (MDA) generation, oxidation of thiol groups, levels of reduced glutathione (GSH) and generation of reactive oxygen species by dichlorofluorescein diacetate (DCFDA). Results: In the analysis of kidney mitochondrial swelling, the obese rats showed lower values only at 10µM Ca+2 concentration vs lean (P<0.05). The kidney mitochondrial MDA (µM/mg protein) was also reduced in obese when compared to lean (P<0.05), even in the presence of the pro - oxidant tert-butylhydroperoxide (t-BOOH). Obese kidney mitochondrial sulphydryl (SH, nmol/mg protein) levels did not show statistical differences when compared to lean DCFDA (nmol/mg protein) levels increased only in the presence of t-BOOH , with no difference between the obese vs lean. Obese rats presented decreased levels of mitochondrial GSH (nmol/mg protein) vs lean rats (81±8 vs 133±18; P<0.05). Conclusion: In summary, our data showed that obese rats had a reduced kidney osmotic mitochondrial swelling if compared to lean rats, suggesting that the mitochondrial permeability could be altered in the obesity. The renal mitochondrial oxidative stress between obese and lean was different only in the evaluation of the MDA, being the antioxidant system reduced in the obese, comparatively to lean. So, in this study we observed that there are differences between the redox system of the obese and lean kidney mitochondria, which can be relevant when the mitochondria would be the target in the treatment of this pathology.