title: Gestational exposure to BDE-99 produces toxicity through upregulation of CYP isoforms and ROS production in the fetal rat liver.
abstract: On gestation day (GD) 6 to GD 19, pregnant Sprague Dawley rats were orally exposed to 0, 0.5, 1, and 2 mg/kg/day to one of the most prevalent polybrominated diphenyl ethers congeners found in humans, 2,2',4,4',5-pentaBDE (BDE-99). All dams were euthanized on GD 20, and live fetuses were evaluated for sex, body weight, and external, internal, and skeletal malformations and developmental variations. The liver from one fetus of each litter was excised for the evaluation of oxidative stress markers and the messenger RNA expression of multiple cytochrome P450 (CYP) isoforms. Exposure to BDE-99 during the gestational period produced delayed ossification, slight hypertrophy of the heart, and enlargement of the liver in fetuses. A transplacental effect of BDE-99, evidenced by the activation of nuclear hormones receptors that induce the upregulation of CYP1A1, CYP1A2, CYP2B1, and CYP3A2 isoforms, was also found in fetal liver. These isoforms are correlated with the activity level of the enzyme catalase and the levels of thiobarbituric acid reactive substances. However, teratogenic effects from BDE-99 exposure were not observed. Clear signs of embryo/fetal toxicity, due to a possible hormonal disruption, were evidenced by a large increase in the CYP system and the production of reactive oxygen species in fetal liver.
authors.affiliation: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, 43201 Reus, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Blanco
authors.forename: Miquel
authors.initials: M
authors.lastname: Mulero
authors.forename: José L
authors.initials: JL
authors.lastname: Domingo
authors.forename: Domènec J
authors.initials: DJ
authors.lastname: Sánchez
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000473:pathology; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D047109:Fetal Development; D005333:Fetus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D007527:Isoenzymes; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D008297:Male; D018811:Maternal Exposure; D018384:Oxidative Stress / Q000187:drug effects; D010544:Peroxidases / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C477694:2,2',4,4',5-brominated diphenyl ether; D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D003577:Cytochrome P-450 Enzyme System; D010544:Peroxidases