title: Application of normobaric hyperoxia therapy for amelioration of haemorrhagic shock-induced acute renal failure.
abstract: BACKGROUND
  Hypoxia resultant from haemorrhagic shock is the primary cause of kidney damage. Application of normobaric hyperoxia therapy (NHT) is an acceptable treatment for acute haemorrhagic shock. We investigated the effect of NHT on amelioration of haemorrhagic shock-induced rat renal failure.
  
  
  METHODS
  Twenty-four Sprague-Dawley rats were subjected to gradual blood withdrawal/reperfusion, followed by 12-h, 24-h or 48-h NHT. Verification/monitoring of intrarenal hypoxia was performed using Hypoxyprobe-TM-1. Subsequently, cystatin C, urea and creatinine were assessed in serum by a Hitachi autoanalyser, and NO, 3-nitro-tyrosine, STAT-8-isoprostane and NF-kB in renal medullae and cortices by specific ELISAs.
  
  
  RESULTS
  In rats subjected to haemorrhagic shock, 12- to 48-h NHT significantly reduced intrarenal Hypoxyprobe-TM-1 stained areas and attenuated augmentation of urea, creatinine and cystatin C. Haemorrhagic shock resulted in a 10-fold drop of intrarenal NO availability. 12-h and 24-h, but not 48-h, NHT significantly increased cortical/medullar NO synthesis, the latter, however, not approaching the pre-shock values. Significant shock-induced accumulation of STAT-8-isoprostane and 3-nitro-tyrosine was further exacerbated by NHT. Haemorrhagic shock activated NF-kB in ischaemic tissues, which was not attenuated by NHT.
  
  
  CONCLUSIONS
  (1) 12- to 48-h NHT decreased intrarenal hypoxia signs and ameliorated deterioration of renal functions in a rat model of haemorrhagic shock-induced renal failure. (2) 12- to 24 h NHT improved bioavailability of NO in cortices/medullae of kidneys recuperating from haemorrhagic shock. (3) If any anti-inflammatory activities were stimulated by NHT, they would not be mediated via the NF-kB pathway. (4) Despite NHT-associated elevation of reactive oxygen species (ROS), early oxygen supply proved mandatory for effective recuperation of ischaemic kidney from detrimental consequences of haemorrhagic shock.
authors.affiliation: Division of Nephrology, Assaf Harofeh Medical Center, Zerifin 70300, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel. efratishai@013.net
authors.forename: Shai
authors.initials: S
authors.lastname: Efrati
authors.forename: Sylvia
authors.initials: S
authors.lastname: Berman
authors.forename: Gadi
authors.initials: G
authors.lastname: Ben Aharon
authors.forename: Yariv
authors.initials: Y
authors.lastname: Siman-Tov
authors.forename: Zhan
authors.initials: Z
authors.lastname: Averbukh
authors.forename: Joshua
authors.initials: J
authors.lastname: Weissgarten
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003404:Creatinine / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D018496:Hyperoxia; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000503:physiopathology; D051996:Transcription Factor RelA; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014508:Urea / Q000097:blood
chemical_list: C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D014508:Urea; D003404:Creatinine; D015232:Dinoprostone