Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury

Markus P. Schneider, Jennifer C. Sullivan, Paul F. Wach, Erika I. Boesen, Tatsuo Yamamoto, Tohru Fukai, David G. Harrison, David M. Pollock, Jennifer S. Pollock

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Extracellular superoxide dismutase (SOD3) is highly expressed in renal tissues and a critical regulator of vascular function. We hypothesized that deletion of SOD3 would attenuate recovery of renal blood flow (RBF) and increase oxidative stress and injury following renal ischemia/reperfusion (I/R). To test this, we evaluated SOD expression and activity, basal superoxide production, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in kidneys from male and female wild-type (WT) and SOD3-knockout mice. RBF, measured using an ultrasonic flow probe, and histological indices of oxidative stress and injury were assessed after 1 h of ischemia. Following ischemia, RBF was attenuated in kidneys from male, but not female, knockout mice compared with their WT counterparts. Total SOD activity was significantly reduced in male knockout compared with WT male mice but was similar in female mice of both genotypes, suggesting upregulated SOD1 activity. Basal superoxide production and NADPH oxidase activity were unrelated to the differences in RBF. After 24 h, kidneys from both genders of knockout mice were found to have more oxidative stress (3-nitrotyrosine immunohistochemistry) and renal cast formation than those from WT mice. Thus, our study found a key role for SOD3 in regulating renal I/R injury.

Original languageEnglish (US)
Pages (from-to)374-381
Number of pages8
JournalKidney International
Volume78
Issue number4
DOIs
StatePublished - Aug 2010

Keywords

  • ischemia
  • oxidative stress
  • renal circulation
  • reperfusion injury
  • superoxide
  • superoxide dismutase

ASJC Scopus subject areas

  • Nephrology

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  • Cite this

    Schneider, M. P., Sullivan, J. C., Wach, P. F., Boesen, E. I., Yamamoto, T., Fukai, T., Harrison, D. G., Pollock, D. M., & Pollock, J. S. (2010). Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury. Kidney International, 78(4), 374-381. https://doi.org/10.1038/ki.2010.141