CONICET | Buscador de Institutos y Recursos Humanos

Mitochondria play an essential role in inflammatory processes such as sepsis or endotoxemia, contributing to organ-cellular redox metabolism, being the energy hub of the cell, and emerging as an important center of action of second messengers. In this work, we aimed to elucidate the energy state, redox balance, and mitochondrial remodeling status in cerebral cortex in an experimental model of endotoxemia. Female Sprague-Dawley rats were subjected to a single dose of LPS (ip 8 mg kg-1 body weight) for 6 h. State 3 O2 consumption and inner mitochondrial membrane potential were found increased, whereas ATP production was observed decreased, possibly indicating a low efficient oxidative phosphorylation process as this scenario was accompanied with a decreased P/O ratio. O2‒ production and both systemic and tissue NO markers were observed increased in treated animals. The existence of nitrated proteins suggests an alteration in the local redox balance and possible harmful effects over the energetic processes. Mitochondrial architecture analysis showed an increase in de novo mitochondrial synthesis (increased expression of PGC-1α and TFAM) and fusion process (increased expression of OPA-1). The observed elongation of mitochondria correlates with the occurrence of mild mitochondrial dysfunction and increased levels of systemic NO. Our work presents novel results that contribute to unravel the mechanism by which the triad endotoxemia-redox homeostasis-energy management interact in the brain cortex, leading to propose an interesting target to base future developing therapeutics for preserving this organ from inflammatory and oxidative damage.