Da Silva 2017 Thesis
|da Silva LA (2017) Efeito do tratamento com N-acetilcisteína sobre dinâmica mitocondrial em modelo animal de isquemia crônica de membros inferiores. Dissertation p54.|
Abstract: The tissue death resulting from ischemic changes is a complex process that involves a series of cell events. The interruption of the bloodstream compromise the oxygen supply, nutrients and metabolites needed for the physiological maintenance of muscle tissue. Among the causes of tissue ischemia we highlight arterial thrombosis caused by atherosclerotic disease, responsible for the cardiac, renal, cerebral and peripheral ischemic changes. The tissue ischemia caused by atherosclerotic disease has great incidence on the current Western population, being responsible for high rates of morbidity and mortality. Given the current situation, We sought to evaluate the role of N-acetylcysteine treatment in animals submitted to the lower members ischemia model. To evaluate the effect of Nac, 21 male Wistar rats weighing 250-300 g were used and they were divided into three groups of 7 animals: (1) Sham, (2) Ischemia, (3) NAC-treated ischemia. The animals were submitted to the process of ischemia induction of the hind limbs through the double electrocoagulation of the common iliac arteries and common femoral, then after the procedure they received a daily oral dose of 30 mg/kg of Nac for 30 days. At the end of the 30 days the solear muscle was taken for assessments of oxygen consumption, autophagy markers (ATG16, ATG3, Beclin, LC3 A/B, Markers of mitofagia PINK e PARKIN, and mitochondrial biogenesis markers NRF-1, PGC-1α and TFAM. The animals submitted to the NAC treatment, there was a significant reduction in the activity of PGC1α and TFAM, markers of mitochondrial biogenesis, as well as the increase in the oxygen consumption, in hypoxia, of animals submitted to chronic lower members ischemia, the autophagy beclina marker was also reduced in relation to untreated animals. There were no significant changes in the concentration of autophagy markers (LC3, ATG3 e ATG16 ), in the levels of PINK and PARKIN – mitophagy marker, as well as in the NRF1 of mitochondrial biogenesis marker. The low concentration of oxygen consumption, in normoxia, in animals submitted to chronic lower members ischemia was not reversed by NAC. In conclusion, the treatment with NAC reverses the increase of oxygen consumption in hypoxia, but this effect does not seem to be directly secondary to the modulation of the processes of autophagy, mitofagia or mitochondrial biogenesis.
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Pharmacology;toxicology Pathology: Cardiovascular Stress:Ischemia-reperfusion, Hypoxia Organism: Rat Tissue;cell: Skeletal muscle
Coupling state: OXPHOS Pathway: F, N, NS HRR: Oxygraph-2k