N-acetyl-cysteine suppresses amniotic fluid and placenta inflammatory cytokine responses to lipopolysaccharide in rats

• Published in: American journal of obstetrics and gynecology 2006, Vol.194 (1), p.268-273
• Main Authors: Beloosesky, Ron, Gayle, Dave A., Amidi, Fataneh, Nunez, Sonia E., Babu, Jooby, Desai, Mina, Ross, Michael G.
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; Amniotic Fluid - metabolism; Animals; Antioxidants - pharmacology; Biological and medical sciences; Cytokines - antagonists & inhibitors; Female; Fetus; Gynecology. Andrology. Obstetrics; Inflammation; Inflammation Mediators - antagonists & inhibitors; Interleukin-10 - blood; Interleukin-6 - blood; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lipopolysaccharides - pharmacology; Maternal infection; Medical sciences; N-acetyl-cysteine; Placenta - metabolism; Pregnancy; Rat; Rats; Rats, Sprague-Dawley; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - metabolism
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2005.06.082

Maternal infections may induce placental, amniotic and, potentially, fetal inflammatory responses. As cytokine responses may be mediated by oxidative stress, we determined whether the antioxidant N-acetyl-cysteine (NAC), can attenuate maternally induced amniotic and placental cytokine responses to maternal infection (modeled by lipopolysaccharide [LPS]). Gestation day 18 pregnant rats were (1) treated with LPS (100 μg/kg, body weight; intraperitoneally) alone; (2) pretreated with NAC (300 mg/kg body weight; intraperitoneally) 30 minutes before LPS; (3) posttreated with NAC 120 minutes after LPS; or (4) treated with NAC 30 minutes before and 120 minutes after LPS. Six hours after LPS administration, maternal serum and amniotic fluid interleukin-6 (IL-6) and IL-10 levels, and placental IL-6 messenger RNA levels were determined. LPS increased maternal serum IL-6 (50 ± 25 to 3444 ± 584 pg/mL) and IL-10 (40 ± 20 to 958 ± 339 pg/mL) and amniotic fluid IL-6 (59 ± 25 to 891 ± 128 pg/mL). Pretreatment and/or posttreatment with NAC attenuated IL-6 in the maternal serum and amniotic fluid and IL-10 in the amniotic fluid. LPS also induced placental IL-6 messenger RNA that was inhibited by treatment with NAC before and after LPS. NAC inhibition of inflammatory responses may protect the fetus from potential long-term sequelae.