Abstract
Sepsis is a public health issue, associated with complications as critical illness polyneuropathy (CIP). This study investigates how mitochondrial dysfunction could contribute to CIP by examining metabolic changes in dorsal root ganglia (DRG) culture from newborn Wistar rats exposed to different concentrations of lipopolysaccharide (5, 10, 50, and 100 μg/mL for 24 or 48 h). Cell viability was assessed using the MTS assay, gene expression related to inflammation and mitochondrial function was analyzed by Real-Time PCR. IL-6 levels of supernatants were measured by ELISA and energetic metabolism was evaluated with the Seahorse MitoStress kit. Exposure to LPS at varying concentrations mainly did not affect cell viability, except at 10 μg/mL for 48 h, where a 7.5% increase was noted. Gene expression analysis showed trends in SOD2 and Fis1, with significant increases in IL-6 and LIF transcripts at 5 and 10 μg/mL. IL-6 release was significant at 50 and 100 μg/mL of LPS. Mitochondrial respiration and glycolytic metabolism exhibited significant changes in oxygen consumption rate and extracellular acidification, particularly at higher LPS concentrations. The findings suggest that LPS induces an inflammatory environment which led to metabolic disturbances in DRG cells, with adaptive responses at 10 and 50 μg/mL of LPS.
Keywords:
dorsal root ganglia; glycolysis; lipopolysaccharide; oxidative phosphorylation.