Maternal N-acetyl-cysteine (NAC) protects the rat fetal brain from inflammatory cytokine responses to lipopolysaccharide (LPS)

Abstract

Objective: Inflammatory cytokines, play a central role in the genesis of preterm parturition and fetal brain injury. Lipopolysaccharide (LPS) may activate cytokine pathways via induction of oxidative stress pathways. We hypothesized that enhanced maternal antioxidant activity may blunt fetal brain inflammatory responses to maternal LPS injection in pregnant rats. Methods: Pregnant Sprague-Dawley rats at 18 and 20 days gestation received intraperitoneal (ip) LPS injection and pre- and post-treatment with the antioxidant N-acetyl-cysteine (NAC) or saline. Six hours after the LPS injection, rats were sacrificed, interleukin (IL)-6 and IL-10 mRNA expression in the fetal brains was determined by real time polymerase chain reaction. Results: Maternal ip LPS induced significant increase in fetal brain IL-6 mRNA expression at E18 (3.1 ± 0.6 vs 1.0 ± 0.10 AU) and E20 (29.01 + 13.06 vs 0.95 + 0.05 AU; p < 0.05) compared to Control, only at E20 maternal LPS induced increase in fetal brain IL-10 compared to control. NAC administered prior to and after LPS significantly reduced fetal brain IL-6 at E18 and E20 and IL-10 at E20. Conclusion: Maternal NAC can protect the fetal brain from inflammatory cytokine responses to maternal LPS injection. These results suggest that NAC may potentially protect fetus from inflammation-associated brain injury and potential long term sequelae.

Keywords::

• Inflammation
• fetal brain
• injury
• NAC

Declaration of Interest: This research was supported by The Morasha Program of the Israel Science Foundation (grant No. 1814 /07).