Gestational exposure to BDE-99 produces toxicity through upregulation of CYP isoforms and ROS production in the fetal rat liver

Toxicological Sciences : an Official Journal of the Society of Toxicology
Jordi BlancoDomènec J Sánchez

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 increas...Continue Reading

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Citations

Dec 11, 2013·International Journal of Molecular Sciences·Jamie E Moscovitz, Lauren M Aleksunes
Jul 11, 2013·World Journal of Gastroenterology : WJG·Giovanni TarantinoCarmine Finelli
Nov 13, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jordi BlancoDomènec J Sanchez
Sep 26, 2015·Reproductive Toxicology·Anna KilanowiczKrystyna Sitarek
Jan 11, 2013·Basic & Clinical Pharmacology & Toxicology·Lílian Cristina PereiraDaniel Junqueira Dorta
Nov 26, 2013·Toxicology Letters·Lucio G CostaClaudia Pellacani
Jun 11, 2016·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Emily W Y TungMichael G Wade

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