Objective To evaluate the effect of N-acetylcysteine(NAC) on lipopolysaccharide(LPS)-sensitized neonatal rats with
hypoxic-ischemic brain damage(HIBD) and possible mechanism except the antioxidant.Methods With the total number of 98 Wistar pups at postnatal day 8 of either sex was used in this study.There were 86 pups which were divided into three groups to evaluate the brain injury:vehicle group(n=29),low dose(25 mg/kg)(n=31) and high
dose NAC(200 mg/kg)(n=26) treatment group.The pups were injected with LPS(0.1 mg/kg)intraperitoneally 3 days before hypoxic-ischemic(HI) insult.Multiple dose of NAC(25 mg/kg or 200 mg/kg) or
vehicle was injected intraperitoneally before and after HI.Brain injury was evaluated 7 days after HI.For the Caspase-3 activity and immunoblotting analysis,the samples were collected at 24 h after
HI treated either with vehicle or high dose NAC(n=6 per group).Results The brain injury volume was significantly reduced by high dose NAC(200 mg/kg) treatment compared with that of vehicle(77% reduction,P<0.001).The tissue loss was reduced 67%(P<0.001) in high dose NAC treated group compared with that of vehicle.However,there was no significant reduction of brain injury in the low dose NAC treatment group compared with vehicle group.(Caspa)-se-3 like activity measurement showed that the activity decreased 53% after high dose NAC treatment(P<0.001) compared with that of vehicle treatment.The immunoblots showed that the active form of Caspase-3,17 kDa band,was abolished by the high dose NAC treatment.Conclusions NAC treatment attenuate LPS-sensitized neonatal HI brain injury is dose dependent.The neuroprotective effect involves Caspase-3 inhibition.
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