title: Ascorbic acid protects against lipopolysaccharide-induced intra-uterine fetal death and intra-uterine growth retardation in mice.
abstract: Lipopolysaccharide (LPS) has been associated with adverse developmental outcomes including embryonic resorption, intra-uterine fetal death (IUFD), intra-uterine growth retardation (IUGR) and preterm labor. Reactive oxygen species (ROS) mediate LPS-induced developmental toxicity. Ascorbic acid is an antioxidant. In the present study, we investigated the effect of ascorbic acid on LPS-induced IUFD and IUGR in mice. All ICR pregnant mice except controls received an intraperitoneal (75 microg/kg, i.p.) injection of LPS daily on gd 15-17. The experiment was carried out in three different modes. In mode A, the pregnant mice were pretreated with a single dose (500 mg/kg, i.p.) of ascorbic acid before LPS. In mode B, the pregnant mice were administered with a single dose (500 mg/kg, i.p.) of ascorbic acid at 3h after LPS. In mode C, the pregnant mice were administered with 500 mg/kg (i.p.) of ascorbic acid at 30 min before LPS, followed by additional dose (500 mg/kg, i.p.) of ascorbic acid at 3h after LPS. The number of live fetuses, dead fetuses and resorption sites was counted on gd 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Results showed that maternally administered LPS significantly increased fetal mortality, decreased fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone. LPS-induced IUFD and IUGR were associated with lipid peroxidation and GSH depletion in maternal liver, placenta and fetal liver. Pre-treatment with ascorbic acid significantly attenuated LPS-induced lipid peroxidation, decreased fetal mortality, and reversed LPS-induced fetal growth and skeletal development retardation. By contrast to pre-treatment, post-treatment with ascorbic acid had less effect on LPS-induced IUFD, although post-treatment significantly attenuated LPS-induced lipid peroxidation and reversed LPS-induced fetal growth and skeletal development retardation. Furthermore, post-treatment with ascorbic acid reduced the protective effects of pre-treatment on LPS-induced IUFD. All these results suggest that pre-treatment with ascorbic acid protected against LPS-induced fetal death and reversed LPS-induced growth and skeletal development retardation via counteracting LPS-induced oxidative stress, whereas post-treatment had less effect on LPS-induced IUFD.
authors.affiliation: Department of Toxicology, Anhui Medical University, Meishan Road, Anhui Province, Hefei 230032, PR China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology / Q000503:physiopathology; D018568:Crown-Rump Length; D005260:Female; D005313:Fetal Death / Q000139:chemically induced / Q000517:prevention & control*; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000517:prevention & control*; D020567:Fetal Weight / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016017:Odds Ratio; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D001205:Ascorbic Acid