The anti-inflammatory agent N-acetyl cysteine exacerbates endotoxin-induced hypoxemia and hypotension and induces polycythemia in the ovine fetus.
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.
Probyn
Megan E
ME
School of Biomedical Sciences, Monash University, Clayton, Vic., Australia. m.probyn@uq.edu.au
Cock
Megan L
ML
Duncan
Jhodie R
JR
Tolcos
Mary
M
Hale
Nadia
N
Shields
Amy
A
Rees
Sandra M
SM
Harding
Richard
R
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D002245:Carbon Dioxide; D010100:Oxygen; D000111:Acetylcysteine