Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||Selenium inhibits renal oxidation and inflammation but not acute kidney injury in an animal model of rhabdomyolysis|
|Citation:||Antioxidants & Redox Signaling, 2013; 18(7):756-769|
|Publisher:||Mary Ann Liebert, Inc. Publishers|
|Anu Shanu, Ludwig Groebler, Hyun Bo Kim, Sarah Wood, Claire M. Weekley, Jade B. Aitken, Hugh H. Harris, and Paul K. Witting|
|Abstract:||Acute kidney injury (AKI) is a manifestation of rhabdomyolysis (RM). Extracellular myoglobin accumulating in the kidney after RM promotes oxidative damage, which is implicated in AKI. AIM: To test whether selenium (Se) supplementation diminishes AKI and improves renal function. RESULTS: Dietary selenite increased Se in the renal cortex, as demonstrated by X-ray fluorescence microscopy. Experimental RM-stimulated AKI as judged by increased urinary protein/creatinine, clusterin, and kidney injury molecule-1 (KIM-1), decreased creatinine clearance (CCr), increased plasma urea, and damage to renal tubules. Concentrations of cholesterylester (hydro)peroxides and F₂-isoprostanes increased in plasma and renal tissues after RM, while aortic and renal cyclic guanidine monophosphate (cGMP; marker of nitric oxide (NO) bioavailability) decreased. Renal superoxide dismutase-1, phospho-P65, TNFα gene, MCP-1 protein, and the 3-chloro-tyrosine/tyrosine ratio (Cl-Tyr/Tyr; marker of neutrophil activation) all increased after RM. Dietary Se significantly decreased renal lipid oxidation, phospho-P65, TNFα gene expression, MCP-1 and Cl-Tyr/Tyr, improved NO bioavailability in aorta but not in the renal microvasculature, and inhibited proteinuria. However, CCr, plasma urea and creatinine, urinary clusterin, and histopathological assessment of AKI remained unchanged. Except for the Se++ group, renal angiotensin-receptor-1/2 gene/protein expression increased after RM with parallel increases in MEK1/2 inhibitor-sensitive MAPkinase (ERK) activity. INNOVATION: We employed synchrotron radiation to identify Se distribution in kidneys, in addition to assessing reno-protection after RM. CONCLUSION: Se treatment has some potential as a therapeutic for AKI as it inhibits oxidative damage and inflammation and decreases proteinuria, albeit histopathological changes to the kidney and some plasma and urinary markers of AKI remain unaffected after RM.|
|Keywords:||Kidney; Animals; Rats; Rats, Sprague-Dawley; Rhabdomyolysis; Disease Models, Animal; Inflammation; Selenium; Tissue Distribution; Dietary Supplements; Male; Acute Kidney Injury|
|Rights:||© Mary Ann Liebert, Inc.|
|Appears in Collections:||IPAS publications|
Environment Institute publications
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.