title: Synergistic effects of pyrrolizidine alkaloids and lipopolysaccharide on preterm delivery and intrauterine fetal death in mice.
abstract: Preterm birth is the leading cause of death for newborn infants, and lipopolysaccharide (LPS) is commonly used to induce preterm delivery in experimental animals. Pyrrolizidine alkaloids (PAs) are widespread and occur in foods, herbs, and other plants. This study was to investigate the synergistic effects of LPS and two representative PAs, retrorsine (RTS) and monocrotaline (MCT), on preterm delivery and fetal death. Pregnant Kunming mice were divided into seven groups: control, RTS, MCT, LPS, RTS+LPS and two MCT+LPS groups. Animals in PAs and PAs+LPS groups were dosed intragastrically with RTS (10mg/kg) or MCT (20 mg/kg or 60 mg/kg) from gestational day (GD) 9 to GD16; mice given LPS were injected intraperitoneally with 150 μg/kg on GD15.5. Latencies to delivery, numbers of pups live and dead at birth were recorded, and livers of live neonates were collected. The incidence of LPS-induced preterm birth was enhanced in dams pretreated with MCT, and combination of PAs and LPS increased fetal mortality from PAs. The enhancement of LPS-induced preterm delivery and fetal demise in animals exposed chronically to PAs and other substances found in foods and beverages consumed widely by humans merits further focused investigation.
authors.affiliation: Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan 430071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Ma
authors.forename: Hao
authors.initials: H
authors.lastname: Kou
authors.forename: Rongze
authors.initials: R
authors.lastname: Sun
authors.forename: Hanxiao
authors.initials: H
authors.lastname: Yang
authors.forename: Charles Vincent
authors.initials: CV
authors.lastname: Smith
authors.forename: Jiang
authors.initials: J
authors.lastname: Zheng
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005313:Fetal Death / Q000139:chemically induced*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D011247:Pregnancy; D047928:Premature Birth / Q000139:chemically induced*; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D011763:Pyrrolizidine Alkaloids; D017392:Thiobarbituric Acid Reactive Substances
keywords: Fetal death; GD; IUGR; LPS; Lipopolysaccharide; MCT; Oxidative injury; PAs; Preterm delivery; Pyrrolizidine alkaloids; ROS; RTS; TBARS; gestational day; intrauterine growth retardation; lipopolysaccharide; monocrotaline; pyrrolizidine alkaloids; reactive oxygen species; retrorsine; thiobarbituric acid reactive substances