title: N-acetylcysteine attenuates glycerol-induced acute kidney injury by regulating MAPKs and Bcl-2 family proteins.
abstract: BACKGROUND
  Rhabdomyolysis-induced acute kidney injury (AKI) accounts for about 10 to 40% of all cases of AKI. It is known that N-acetylcysteine (NAC) is effective in various experimental renal injury models; however, little information is available about the rat model of glycerol-induced rhabdomyolysis. In this study, we hypothesize that NAC plays a renoprotective role via the anti-apoptotic pathway.
  
  
  METHODS
  Male Sprague-Dawley rats were divided into four groups: (i) saline control group, (ii) NAC-treated group (N-acetylcysteine) (150 mg/kg), (iii) glycerol-treated group (50%, 8 ml/kg, IM) and (iv) NAC plus glycerol-treated group. Rats were sacrificed at 24 h after glycerol injection, and the blood and renal tissues were harvested.
  
  
  RESULTS
  Glycerol administration caused severe renal dysfunction, which included marked renal oxidative stress, significantly increased blood urea nitrogen (BUN) and serum creatinine levels. Histopathological findings, such as cast formation and tubular necrosis, confirmed renal impairment. We noted a marked activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p-38, in the glycerol-treated group. We also observed high expression of Bax and Bad but only weak expression of Bcl-2 and Bcl-xL in the glycerol-treated group. However, NAC pretreatment significantly improved renal function and decreased the activation of ERK, JNK, Bax and Bad, whereas it increased Bcl-2 and Bcl-xL.
  
  
  CONCLUSIONS
  These results demonstrate that NAC protects against renal dysfunction, morphological damage and biochemical changes via the anti-apoptotic pathway in the glycerol-induced rhabdomyolysis model in rats.
authors.affiliation: Clinical Research Institute, Gyeongsang National University Hospital, Jinju, Gyeongnam, Republic of Korea.
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Lee
authors.forename: Myeong Hee
authors.initials: MH
authors.lastname: Jung
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Yeo
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jung Ill
authors.initials: JI
authors.lastname: Yang
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
authors.forename: Se-Ho
authors.initials: SH
authors.lastname: Chang
authors.forename: Dong Jun
authors.initials: DJ
authors.lastname: Park
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005978:Glutathione / Q000032:analysis; D005990:Glycerol / Q000633:toxicity*; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000032:analysis; D051020:bcl-X Protein / Q000032:analysis
chemical_list: C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D005978:Glutathione; D005990:Glycerol; D000111:Acetylcysteine