Renal injury is one of the severe and common complications that occurs early in neonates with
asphyxia, and
reactive oxygen species have been implicated to play an important role on its pathogenesis. Improved renal recovery has been shown previously with
N-acetyl-l-cysteine (NAC) in various
acute kidney injuries. Using a subacute swine model of neonatal
hypoxia-reoxygenation (H/R), we examined whether NAC can sustain its beneficial effect on renal recovery for 48 h. Newborn piglets were randomly assigned into a
sham-operated group (without H/R, n = 6) and two H/R experimental groups (n = 8 each) with 2 h normocapnic alveolar
hypoxia and 1 h 100%
oxygen of reoxygenation followed by 21%
oxygen for 47 h. Five minutes after reoxygenation, piglets received either
normal saline (H/R control) or NAC (150-mg/kg bolus and 20 mg/kg per hour i.v. for 24 h) in a blinded, randomized fashion. All piglets were acidotic and in
cardiogenic shock after
hypoxia. Treating the piglets with NAC significantly increased both renal blood flow and
oxygen delivery throughout the reoxygenation period.
N-acetyl-l-cysteine treatment also improved the renal function with the attenuation of elevated urinary N-acetyl-β-d-
glucosaminidase activity and plasma
creatinine concentration observed in H/R controls (both P < 0.05). The tissue levels of
lipid hydroperoxides and
caspase 3 in the kidney of NAC-treated animals were significantly lower than those of H/R controls. Conclusively, postresuscitation administration of NAC elicits a prolonged beneficial effect in improving renal functional recovery and reducing oxidative stress in newborn piglets with H/R insults for 48 h.