Synergistic effects of pyrrolizidine alkaloids and lipopolysaccharide on preterm delivery and intrauterine fetal death in mice |
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Authors: | Yu Guo Zhenguo Ma Hao Kou Rongze Sun Hanxiao Yang Charles Vincent Smith Jiang Zheng Hui Wang |
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Affiliation: | 1. Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan 430071, China;2. Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071, China;3. Center for Developmental Therapeutics, Seattle Children''s Research Institute, Division of Gastroenterology, Department of Pediatrics, University of Washington, Seattle, WA 98101, USA;4. Shenyang Pharmaceutical University, Shenyang 110016, China |
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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 (10 mg/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. |
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Keywords: | LPS, lipopolysaccharide PAs, pyrrolizidine alkaloids RTS, retrorsine MCT, monocrotaline GD, gestational day IUGR, intrauterine growth retardation ROS, reactive oxygen species TBARS, thiobarbituric acid reactive substances |
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