Ouabain contributes to kidney damage in a rat model of renal ischemia-reperfusion injury

Luca Villa, Roberta Buono, Mara Ferrandi, Isabella Molinari, Fabio Benigni, Arianna Bettiga, Giorgia Colciago, Masami Ikehata, Elisabetta Messaggio, Maria Pia Rastaldi, Francesco Montorsi, Andrea Salonia, Paolo Manunta

Research output: Contribution to journalArticle

Abstract

Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 μg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 μg/kg/day rostafuroxin for four weeks. In group 1, 2–3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO.

Original languageEnglish
Article number1728
JournalInternational Journal of Molecular Sciences
Volume17
Issue number10
DOIs
Publication statusPublished - Oct 14 2016

Keywords

  • Na-K ATPase
  • Nephrin
  • Ouabain
  • Renal damage
  • Rostafuroxin
  • Warm ischemia

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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