title: Assessment of neurotoxic effects and brain region distribution in rat offspring prenatally co-exposed to low doses of BDE-99 and methylmercury.
abstract: Exposure to polybrominated diphenyl ether (PDBE) and methylmercury (MeHg) can occur simultaneously as both contaminants are found in the same food sources, especially fish, seafood, marine mammals and milk. The aim of this study was to assess the effects of exposure to low levels of MeHg (2.0 μg mL(-1) in drinking water) and BDE-99 (0.2 mg kg(-1) d(-1)) from gestational day 6 to postnatal day (PND) 21, alone and in combination, on neurobehavioral development and redox responses in offspring. The present study demonstrated an interaction due to co-exposure with low doses of MeHg and BDE-99 enhanced developmental neurotoxic effects. These effects were manifested as the delayed appearance of negative geotaxis reflexes, impaired motor coordination, and induction of oxidative stress in the cerebellum. In particular, the cerebellum may be a sensitive target for combined MeHg and BDE-99 toxicity. The neurotoxicity of low dose MeHg was exacerbated by the presence of low dose of BDE-99. It is concluded that prenatal co-exposure to MeHg and BDE-99 causes oxidative stress in the cerebellum of offspring by altering the activity of different antioxidant enzymes and producing free radicals. Hg retention was not affected by co-exposure to BDE-99. However, MeHg co-exposure seemed to increase BDE-99 concentrations in selected brain regions in pups compared to pups exposed to BDE-99 only. These results showed that the adverse effects following prenatal co-exposure to MeHg and BDE-99 were associated with tissue concentrations very close to the current human body burden of this persistent bioaccumulative compound.
authors.affiliation: School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; School of Environmental and Safety Engineering, Changzhou University, Changzhou, Jiangsu 213164, China.
authors.forename: Wenchang
authors.initials: W
authors.lastname: Zhao
authors.affiliation: School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: jpcheng@sjtu.edu.cn.
authors.forename: Jinping
authors.initials: J
authors.lastname: Cheng
authors.affiliation: School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Gu
authors.affiliation: School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Basic Medical Science, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Fujimura
authors.affiliation: School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D012727:Sex Characteristics
chemical_list: C477694:2,2',4,4',5-brominated diphenyl ether; D055768:Halogenated Diphenyl Ethers; D008767:Methylmercury Compounds; D009498:Neurotoxins
keywords: Methylmercury; Neurobehavioral development; Polybrominated diphenyl ether; Prenatal co-exposure; Redox response