title: Emodin prevents ethanol-induced developmental anomalies in cultured mouse fetus through multiple activities.
abstract: BACKGROUND
  Maternal alcohol ingestion on pregnant period causes fetal alcohol syndrome including psychological and behavioral problems, and developmental abnormality. In this study, we investigated the effect of emodin, an active anthraquinone component found in the roots and bark of the genus Rhamnus (Buckthorn), on ethanol-induced teratogenesis during embryonic organogenesis.
  
  
  METHODS
  We cultured mouse embryos on embryonic day 8.5 for 2 days with ethanol (5 μl/3 ml) and/or emodin (1×10(-5) and 1×10(-4) μg/ml) using a whole embryo culture system and then investigated the developmental evaluation, superoxide dismutase (SOD) activity, and expression patterns of cytoplasmic SOD (SOD1), mitochondrial SOD (SOD2), cytosolic glutathione peroxidase (cGPx), tumor necrosis factor-α (TNF-α), caspase 3, and hypoxia inducible factor 1α (HIF-1α).
  
  
  RESULTS
  Morphological parameters, including growth in yolk sac and fetal head, body length, and development of the central nervous system, circulation system, sensory organs, skeletal system, and limbs in embryos exposed to ethanol were significantly decreased compared to those of the normal control group, but co-treatment with emodin (1 × 10(-5) and 1 × 10(-4) μg/ml) significantly improved these parameters. Furthermore, the reduced levels of SOD activity, and SOD1, SOD2, cGPx, and HIF-1α and the increased gene levels of TNF-α and caspase-3 due to ethanol exposure were significantly restored by cotreatment with emodin. Birth Defects Res (Part B) 98:268-275, 2013. © 2013 Wiley Periodicals, Inc.
  
  
  CONCLUSIONS
  This study revealed that cotreatment with emodin significantly prevented teratogenesis induced by ethanol, not only by modulating hypoxia and antioxidant enzymes, but also by attenuating the enhanced levels of TNF-α and caspase 3 in cultured embryos. Therefore, emodin may be an effective preventive agent for ethanol-induced teratogenesis.
authors.affiliation: College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Yon
authors.forename: Chunmei
authors.initials: C
authors.lastname: Lin
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Hong-Seok
authors.initials: HS
authors.lastname: Baek
authors.forename: Beom Jun
authors.initials: BJ
authors.lastname: Lee
authors.forename: Young Won
authors.initials: YW
authors.lastname: Yun
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Nam
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D046149:Embryo Culture Techniques; D047108:Embryonic Development / Q000187:drug effects*; D004642:Emodin / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000002:abnormalities* / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013723:Teratogens / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015017:Yolk Sac / Q000187:drug effects / Q000196:embryology
chemical_list: D000975:Antioxidants; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators; D012333:RNA, Messenger; D013723:Teratogens; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3; D004642:Emodin