title: Protective effects of edaravone, a free radical scavenger, on lipopolysaccharide-induced acute kidney injury in a rat model of sepsis.
abstract: OBJECTIVE
  Acute kidney injury (AKI) is a frequent complication of sepsis. The present work examined the therapeutic potential of edaravone (EDA), a free radical scavenger, for inhibiting sepsis-induced renal injury.
  
  
  METHODS
  Saline and lipopolysaccharide (LPS) were injected intraperitoneally at a dose of 10 mg/kg of body weight. EDA, 3-methyl-1-phenyl-pyrazolin-5-one, was administrated intravenously at a dose of 3 mg/kg of body weight to male Wistar rats. Wistar rats were divided into four groups: treatment with LPS alone, treatment with LPS followed by EDA administration, treatment with saline followed by EDA administration, and untreated controls.
  
  
  RESULTS
  Administration of LPS caused a significant increase in BUN and serum creatinine levels with concurrent pathological alterations in kidney tissues. EDA treatment relieved all these changes. Moreover, EDA reduced LPS-induced elevation of serum TNF-α and IL-6 in rats. Furthermore, EDA could prevent mitochondrial membrane potential loss induced by LPS and reverse the changes in mitochondrial antioxidant (such as T-AOC, SOD, CAT, and GSH) and mitochondrial MDA levels. TUNEL staining of the kidney sections and immunoblot analysis on renal cortical lysates showed that EDA treatment resulted in reduced number of apoptotic cells, which occurred concomitantly with decreased levels of cytochrome c and cleaved caspase 3. Following LPS treatment of rat renal tubular cells, mitochondrial fragmentation was observed prior to apoptosis, which was inhibited by EDA.
  
  
  CONCLUSIONS
  EDA prevents LPS-induced AKI not only by reducing the production of inflammatory cytokines, but also by attenuating oxidative damage in renal mitochondria, mitochondrial fragmentation, and apoptosis of renal cells.
authors: Department of Pediatry, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.
authors: Lin
authors: L
authors: Liu
authors: Division of Pediatric Nephrology Pediatric Medical Center, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
authors: Yijin
authors: Y
authors: Song
authors: Department of Pediatry, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.
authors: Ming
authors: M
authors: Zhao
authors: Division of Pediatric Nephrology Pediatric Medical Center, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China. yizhuwen1969@163.com.
authors: Zhuwen
authors: Z
authors: Yi
authors: Department of Pediatrics, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510280, P.R. China. zqy_88@163.com.
authors: Qiyi
authors: Q
authors: Zeng
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007684:Kidney Tubules / Q000166:cytology; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D063154:Mitochondrial Dynamics / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016166:Free Radical Scavengers; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000077553:Edaravone; D000983:Antipyrine
keywords: Acute kidney injury; Edaravone; LPS; Mitochondrial fragmentation; Sepsis