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Evaluation of Glutaredoxin 1 as a Novel Marker of Renal Damage after Ischemia‐Reperfusion Injury in Mice
Author(s) -
Godoy Jose R.,
O’Sullivan Meghan,
Bethel-Lebel Herdest,
Moncada Marcela H.,
Illanes Oscar,
Gellert Manuella,
Lillig Christopher Horst
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06530
Subject(s) - creatinine , renal function , kidney , medicine , proteinuria , glutaredoxin , kidney disease , ischemia , western blot , urine , pathology , acute kidney injury , urology , oxidative stress , chemistry , biochemistry , thioredoxin , gene
Renal ischemia‐reperfusion injury (IRI) is a significant cause of acute renal failure and delayed graft function in clinical patients. Tissue damage in renal IRI is caused in part by the activation of the immune response and the generation of reactive oxygen species (ROS), both taking place mainly during the reperfusion phase, once the blood supply to the tissue is restored. Glutaredoxin 1 (Grx1), a cytosolic protein that reduces protein disulfides as well as glutathionylated proteins, plays a protective role in ROS‐mediated damage to the cell. In a previous work, we detected increased levels of Grx1 in the urine of mice 24h after renal IRI 1. Recently, Grx1 was shown to be elevated in the serum of patients with chronic kidney disease 2. To determine the usefulness of Grx1 as a possible biomarker of ischemic renal damage we evaluated serum, urinary, as well as intra‐renal levels of Grx1 in a mouse model of renal IRI. Different reperfusion times (4h, 8h, 16h, 24h, 48h, 96h, and 168h) were compared in order to follow Grx1 fluctuation levels in the kidney, serum, and urine. Serum Grx1 levels, analyzed by ELISA, were correlated with several renal function parameters such as serum creatinine, proteinuria, glomerular diameter, and tubular thickness. After IRI, Grx1 serum levels increased much earlier than creatinine (4h versus 24h). Western blot analyses showed a decrease of Grx1 in the kidney of mice with surgically induced IRI, compared to the sham group. Additionally, immunohistochemistry revealed an increased apical localization of Grx1 in cells of the distal convoluted tubules of the mice exhibiting IRI. Urinary levels of Grx1, even if increased in the first hours after renal IRI, were not significantly altered. These findings provide initial supporting evidence for the use of a redox protein such as Grx1 as a novel biomarker for assessing renal damage under experimental conditions. Further studies are necessary to validate these results. Support or Funding Information This work was funded by the Center of Integrative Mammalian Research of Ross University School of Veterinary Medicine.References 1 Godoy JR , Oesteritz S , Hanschmann EM , Ockenga W , Ackermann W , Lillig CH. Segment-specific overexpression of redoxins after renal ischemia and reperfusion: protective roles of glutaredoxin 2, peroxiredoxin 3, and peroxiredoxin 6 . Free Radic Biol Med. 2011 Jul 15 ; 51 ( 2 ): 552 – 612 Levin A , Nair D , Qureshi AR , Bárány P , Heimburger O , Anderstam B , Stenvinkel P , Bruchfeld A , Ungerstedt JS. Serum Glutaredoxin Activity as a Marker of Oxidative Stress in Chronic Kidney Disease: A Pilot Study . Nephron. 2018 ; 140 ( 4 ): 249 – 256