Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury.

Autor: Villa L; Division of Experimental Oncology/Unit of Urology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. villa.luca@hsr.it., Buono R; Division of Experimental Oncology/Unit of Urology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. buono@usc.edu., Ferrandi M; Prassis Sigma-Tau Research Institute, Settimo Milanese, 20019 Milan, Italy. mara.ferrandi@gmail.com., Molinari I; Prassis Sigma-Tau Research Institute, Settimo Milanese, 20019 Milan, Italy. isabella.molinari8@gmail.com., Benigni F; Division of Experimental Oncology/Unit of Urology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. benigni.fabio@hsr.it., Bettiga A; Division of Experimental Oncology/Unit of Urology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. bettiga.arianna@hsr.it., Colciago G; Division of Experimental Oncology/Unit of Urology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. colciago.giorgia@hsr.it., Ikehata M; Renal Research Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico & Fondazione D'Amico, 20122 Milan, Italy. aquamarine0321@libero.it., Messaggio E; Division of Genetics and Cell Biology, Genomics of Renal Diseases and Hypertension Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. messaggio.elisabetta@hsr.it., Rastaldi MP; Renal Research Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico & Fondazione D'Amico, 20122 Milan, Italy. mariapia.rastaldi@policlinico.mi.it., Montorsi F; Division of Experimental Oncology/Unit of Urology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. montorsi.francesco@hsr.it.; Chair of Urology, Università Vita Salute San Raffaele, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. montorsi.francesco@hsr.it., Salonia A; Division of Experimental Oncology/Unit of Urology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. salonia.andrea@hsr.it.; Chair of Urology, Università Vita Salute San Raffaele, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. salonia.andrea@hsr.it., Manunta P; Division of Genetics and Cell Biology, Genomics of Renal Diseases and Hypertension Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. manunta.paolo@hsr.it.; Chair of Nephrology, Università Vita Salute San Raffaele, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. manunta.paolo@hsr.it.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2016 Oct 14; Vol. 17 (10). Date of Electronic Publication: 2016 Oct 14.
DOI: 10.3390/ijms17101728
Abstrakt: 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.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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