Sims 2014 FASEB J
|Sims C, Patil N, MacMillian-Crow LA, Mayeux P (2014) Mitochondrial superoxide generation in the rat pup kidney during sepsis. FASEB J 28:1063.7.|
Abstract: Sepsis is a leading cause of acute kidney injury (AKI) and mortality in children. In order to develop new therapies, it is critical to understand the development of pediatric sepsis and its effects. In this study, we used a clinically relevant cecal ligation and puncture (CLP) model of peritonitis in rat pups 17-19 days old to characterize the development of sepsis-induced AKI. CLP produced severe sepsis demonstrated by hypothermia and a time-dependent renal microcirculatory failure. Analysis of the renal microcirculation using intravital video microscopy showed a decrease in the number of continuously flowing cortical capillaries and an increase in capillaries with no flow. Renal microcirculatory failure was associated with an increase in mitochondrial superoxide generation as measured using MitoSOX Red. These effects were observed as early as 6h after CLP and were sustained through 18h. To determine if mitochondria dysfunction leads to superoxide generation, high-resolution respirometry (HRR) was used in fresh tissue biopsies to measure the activities of complexes I, II/III, and IV. HRR showed that CLP did not produce changes in any of the mitochondrial complexes at these early time points studied. Therefore, sepsis does not appear to cause severe mitochondrial dysfunction in rat pups despite an increase in mitochondrial superoxide generation.
• O2k-Network Lab: US PA Philadelphia Sims CA
Labels: MiParea: Respiration Pathology: Sepsis
Preparation: Permeabilized tissue
Pathway: N, CIV, NS HRR: Oxygraph-2k