A dual effect of N-acetylcysteine on lipopolysaccharide-induced fetal damage in mice / 中国药理学通报

ABSTRACT

Aim To investigate the effect of N-acetylcysteine (NAC) pretreatment/posttreatment on lipopolysaccharide (LPS)-induced intra-uterine fetal death (IUFD) and intra-uterine growth retardation (IUGR) in mice.Methods In the first experiment,all pregnant mice except controls received an intraperitoneal (75 ?g?kg-1) injection of LPS on gd 15~17.In LPS+NAC groups,the pregnant mice were treated with NAC before and/or after LPS. The saline-and NAC-treated pregnant mice served as controls. The dams were sacrificed on gd 18. In the second experiment,all pregnant mice except controls received an intraperitoneal (75 ?g?kg-1) injection of LPS on gd 15. In LPS+NAC groups,the pregnant mice were treated with NAC before and/or after LPS. The saline-and NAC-treated pregnant mice served as controls. The dams were sacrificed at 1.5 h or 6 h after LPS.Results pretreatment with NAC significantly alleviated LPS-induced fetal mortality and reversed LPS-induced growth development retardation.Correspondingly,pretreatment with NAC significantly attenuated LPS-induced elevation in TNF-? concentration in maternal serum and amniotic fluid and lipid peroxidation in maternal and fetal livers. By contrast to pretreatment,posttreatment with NAC had no effect on LPS-induced TNF-? production and lipid peroxidation,and did not protect against LPS-induced IUFD and IUGR and in fact aggravated LPS-induced preterm labor.Conclusion Pretreatment with NAC attenuates LPS-induced IUFD and IUGR,whereas posttreatment with NAC aggravates LPS-induced preterm labor.