Selenium Inhibits Renal Oxidation and Inflammation But Not Acute Kidney Injury in an Animal Model of Rhabdomyolysis

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 F 2 -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, TNFa 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, TNFa 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. Antioxid Redox Signal. 18, 756-769.

Specific Macrophage Subtypes Influence the Progression of Rhabdomyolysis-Induced Kidney Injury

“…First, myoglobin exerts a direct toxic effect on the proximal tubule, prompting proximal epithelial cells to secrete macrophagerecruiting chemokines such as Ccl2 and Ccl7, as previously shown in the distal tubule 33 and substantiated by data obtained in vitro.…”

A New Chiral Pyrrolyl α-Nitronyl Nitroxide Radical Attenuates β-Amyloid Deposition and Rescues Memory Deficits in a Mouse Model of Alzheimer Disease

“…F2-isoprostanes (non-enzymatic oxidation of arachidonic acid) are considered as markers of oxidative stress [24]. F2-isoprostanes were determined with an immunoassay kit (Cayman, Ann Arbor, MI) according to the manufacturer's instructions [25].…”

Dietary Selenium Status Regulates the Transcriptions of Selenoproteome and Activities of Selenoenzymes in Chicken Kidney at Low or Super-nutritional Levels

“…Gpx activity is essential for avoiding peroxide-generated oxidative damage and is provided by different families of enzymes, namely selenoglutathione peroxidases (Gpx; EC 1.11.1.9; glutathione: hydrogen-peroxide oxidoreductase) [25]. The thioredoxin (Trx) system catalyzes the reduction of protein disulfides such as in ribonucleotide reductase, an enzyme essential for DNA synthesis [26]; thioredoxin peroxidases (peroxiredoxins), critical enzymes in the defense against oxidative stress [27]; and protein disulfide isomerase (PDI). Most selenoproteins in the kidney are intracellular enzymes with their activities relying upon a single selenocysteine residue in their main structures [28].…”