title: The anti-inflammatory agent N-acetyl cysteine exacerbates endotoxin-induced hypoxemia and hypotension and induces polycythemia in the ovine fetus.
abstract: BACKGROUND
  Lipopolysaccharide (LPS) delivered acutely to the ovine fetus induces cerebral white matter injury and brain inflammation. N-acetyl cysteine (NAC) is potentially neuroprotective as it blocks the production of inflammatory cytokines and increases glutathione levels; however, it is unknown whether NAC affects the physiological status of the fetus already exposed to an inflammatory environment.
  
  
  OBJECTIVE
  Our objective was to determine whether NAC influences the physiological effects of LPS exposure in the ovine fetus.
  
  
  METHODS
  Catheterized fetal sheep underwent one of four treatments (saline, n = 6; LPS, n = 6; LPS + NAC, n = 6; NAC, n = 3) on 5 consecutive days from 95 days of gestation (term approximately 147 days). Fetal arterial pressure and heart rate were recorded and blood samples collected.
  
  
  RESULTS
  LPS administration resulted in fetal hypoxemia and hypotension; simultaneous treatment with NAC exacerbated these effects and induced polycythemia. NAC treatment alone had no effect on the fetus.
  
  
  CONCLUSIONS
  In the presence of LPS, NAC compromises fetal physiological status, suggesting that it may not be a suitable antenatal treatment for a fetus with evidence of inflammation.
authors.affiliation: School of Biomedical Sciences, Monash University, Clayton, Vic., Australia. m.probyn@uq.edu.au
authors.forename: Megan E
authors.initials: ME
authors.lastname: Probyn
authors.forename: Megan L
authors.initials: ML
authors.lastname: Cock
authors.forename: Jhodie R
authors.initials: JR
authors.lastname: Duncan
authors.forename: Mary
authors.initials: M
authors.lastname: Tolcos
authors.forename: Nadia
authors.initials: N
authors.lastname: Hale
authors.forename: Amy
authors.initials: A
authors.lastname: Shields
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Rees
authors.forename: Richard
authors.initials: R
authors.lastname: Harding
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005865:Gestational Age; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D010092:Oximetry; D010100:Oxygen / Q000378:metabolism; D011086:Polycythemia / Q000139:chemically induced* / Q000378:metabolism; D012756:Sheep
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D002245:Carbon Dioxide; D010100:Oxygen; D000111:Acetylcysteine