title: Evaluations of lipid peroxidation and inflammation in short-term glycerol-induced acute kidney injury in rats.
abstract: Rhabdomyolysis is characterised by acute kidney injury (AKI) resulting from skeletal muscle injury. Lipid peroxidation-mediated oxidant injury and pro-inflammatory cytokine-mediated inflammatory response play critical roles in the pathogenesis of rhabdomyolysis-induced AKI. The present study aimed to investigate the short-term effects of both lipid peroxidation and inflammatory responses on rhabdomyolysis-induced AKI in a rat model of glycerol-induced rhabdomyolysis. Rhabdomyolysis was induced by the intramuscular injection of 50% glycerol in saline (10 mL/kg) into the hind limbs of rats. Rats were killed 1 or 3 hours after glycerol injection. Time-dependent increases in serum biochemical parameters, including blood urea nitrogen, creatinine, lactate dehydrogenase and creatine phosphokinase levels, were observed 1 hour after glycerol injection. In kidneys, glycerol injection resulted in histopathological changes such as renal tubular injury and renal tubular myoglobin deposition. Levels of Nε-(hexanoyl)lysine-modified, 4-hydroxy-2-nonenal-modified, and nitrotyrosine-modified proteins in rat kidneys were unaltered at 1 hour after glycerol injection, but increased significantly at 3 hours. Increases in renal nitric oxide production and the expression levels of inducible nitric oxide synthase, interleukin-6 and tumour necrosis factor-α in the renal parenchyma were observed at 1 hour after glycerol injection and plateaued at 3 hours. Our findings suggest that the pro-inflammatory cytokine-mediated inflammatory response may cause rhabdomyolysis-induced AKI very shortly after glycerol injection, and lipid peroxidation-mediated oxidant injury may promote the development of these pathophysiological processes.
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan. akina.legm@gmail.com.|Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. akina.legm@gmail.com.
authors.forename: Akina
authors.initials: A
authors.lastname: Nara
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yajima
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Nagasawa
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hoshioka
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hirotaro
authors.initials: H
authors.lastname: Iwase
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005990:Glycerol / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D005990:Glycerol
keywords: acute kidney injury; glycerol; inflammation; lipid peroxidation; rhabdomyolysis