Extracellular superoxide dismutase is necessary to maintain renal blood flow during sepsis development

Abstract

BackgroundExtracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow.MethodsSepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated.ResultsAn increase in ECSOD content was associated with decreased 3-nitrotyrosine levels. These events were associated with an increase in pVASP content and maintenance of renal blood flow. Moreover, previous treatment with a SOD inhibitor increased nitrotyrosine content and reduced renal blood flow.ConclusionsECSOD appears to have a major role in decreasing peroxynitrite formation in the renal artery during the early stages of sepsis development, and its application can be important in renal blood flow control and maintenance during septic insult.

Extracellular superoxide dismutase, a molecular transducer of health benefits of exercise

“…These findings strongly support that enhanced EcSOD expression from skeletal muscle or other tissues/organ, which can be redistributed to the lung tissue, could be a viable preventative/therapeutic measures in reducing the risk and severity of ALI/ARDS. Considering the current outbreak of the 2019 Novel Corona virus infection (COVID- 19), which is an infectious disease that leads to progressive ALI/ARDS in many patients (6,103,107,113), it is conceivable that regular exercise might be effective in preventing while EcSOD gene/protein therapy might be effective in treating ALI/ARDS under the condition of COVID-19 infection.…”

“…Acute kidney injury (AKI). Mouse models in which the EcSOD gene is mutated or SOD inhibitors are used suggest protective role of EcSOD against renal injury (19,45,95,104).…”

“…EcSOD -/mice were more susceptible to histological damage, oxidative stress and increased serum creatinine caused by adverse drug reaction (104). Similarly, when SOD inhibitor was used in a rat sepsis model induced by cecal ligation-puncture (CLP), renal blood flow decreased and nitrotyrosine content increased 48 hours post CLP (19). EcSOD has also been shown to be protective against renal ischemia/reperfusion injury as demonstrated by increased nitrotyrosine and increased renal cast formation 24 hours post ischemia/reperfusion in EcSOD -/compared with wild type mice (95).…”

The Effect of Superoxide Dismutase on Inhibition of Acute Kidney Injury Induced by Sepsis Based on Kidney Tissue Histology and Murine Sepsis Score

“…Sepsis is a complex syndrome characterized by an imbalance between proinflammatory and anti-inflammatory responses to pathogens [ 9 ]. During the development of sepsis, a large number of reactive oxygen species (ROS) and nitric oxide (NO) will be produced [ 12 ].…”

“…One of the primary antioxidants responsible for counteracting oxidative stress is superoxide dismutase (SOD). Constantino et al [ 9 ] stated that SOD is one of the natural antioxidant enzymes found in body cells due to several factors. As you grow older, this antioxidant activity can decrease so that antioxidants from outside the body are needed, one of which is Glisodin, a synthetic SOD.…”