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Toxicol Lett. 2013 Aug 29;221(3):212-8. doi: 10.1016/j.toxlet.2013.06.238. Epub 2013 Jul 4.

Synergistic effects of pyrrolizidine alkaloids and lipopolysaccharide on preterm delivery and intrauterine fetal death in mice.

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  • 1Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan 430071, China.


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.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.


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

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