Abstract
Fetal hypoxia–ischemia can lead to a common pathway of perinatal brain injury marked by inflammation and cellular apoptosis. N-acetyl cystein (NAC) is a known anti oxidant and anti inflammatory agent. We sought to determine the neuro-protective effect of maternal NAC on offspring exposed to hypoxia Newborn Sprague-Dawley rats n=30 (from 6 litter)were randomly allocated to 3 study groups(n=10 each). Group 1 were subjected to hypoxia protocol (HYP; 5% O2 for 10 min) thrice daily beginning on day 1 of life for 5 days. Group 2were subject to hypoxia protocol and received NAC (300mg/kg IP) following each hypoxia episode (HYP-NAC), group3 control (CTL) received no intervention. Group 4 included pups of dams treated once daily with NAC (300mg/kg IV) for the last 3 days of pregnancy and pups subject to hypoxia protocol (n=10). Pups were sacrificed on day five of life. Brains harvested for NFkB p65 (NFkB), nNOS, caspase3, TNF-α, IL-6 protein levels and apoptosis (western blot, tunnel staining) and blood for IL-6 levels (ELISA) HYP offspring had significantly increased brain levels of NFkB, nNOS, TNFα and IL-6 compared to CTL,(2.56±0.1 vs 0.56±0.1 u; 2.3±0.09 vs 0.65±0.05u; 2.5±0.16 vs 1.13±0.18 u; 2.55±0.1 vs 0.9±0.3u; respectively, P< 0.05).NAC treatment to dams (NAC-HYP) dramatically decreased newbornbrain NFkB, nNOS, TNFα and IL-6 levels compared to HYP offspring (0.65±0.17u; 0.76±0.05 u; 0.7±0.16 u; 0.56±0.05 u,respectively P< 0.05) to levels similar to control. Caspase3 protein levelsand tunnel staining were similar in CTL and HYP offspring, while NAC-HYP offspring had significantly less caspase 3 and tunnel staining. There was no difference in offspring serum IL6 protein levels among CTL, HYP and NAC-HYP while HYP-NAC group had higher levels. Prophylactic NAC to dams during pregnancy provided long term neuroprotectionto offspring exposed to hypoxia long after NAC was administered. NAC to dams decreased offspring apoptosis to less than control.These findings suggest that NAC may be used for neuroprotection in cases of suspected fetal hypoxia during labor
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