title: Subacute oral toxicity of BDE-15, CDE-15, and HODE-15 in ICR male mice: assessing effects on hepatic oxidative stress and metals status and ascertaining the protective role of vitamin E.
abstract: The present study examined the effects of oral exposure of 4,4'-dibromodiphenyl ether (BDE-15), 4,4'-dichlorodiphenyl ether (CDE-15), and 4,4'-dihydroxydiphenyl ether (HODE-15) on hepatic oxidative stress (OS) and metal status in Institute of Cancer Research (ICR) male mice. Furthermore, the role of vitamin E in ameliorating potential OS caused by BDE-15, CDE-15, and HODE-15 was investigated. Three groups of mice were exposed to 1.20 mg/kg(body weight)/day of each of the three toxicants for 28 days. Results showed that none of the three toxicants altered growth rates of mice, but significantly increased (P<0.05) relative liver weights and decreased relative kidney weights. Pathological changes including cell swelling, inflammation and vacuolization, and hepatocellular hypertrophy in livers were observed. Significant decreases (P<0.05 and P<0.01) in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity, and glutathione (GSH) levels, together with increases in malondialdehyde (MDA) content were recorded in all toxicant-treated groups. Hepatic copper levels increased in all toxicant-treated groups. Hepatic zinc levels decreased in the liver of BDE-15-treated mice, whereas they increased in the livers of CDE-15-treated and HODE-15-treated mice. In conclusion, daily exposure to the three toxicants perturbed metal homeostasis and increased OS in mouse liver. Experimental data indicated the hepatic oxidative toxicity of the three toxicants followed the order BDE-15<HODE-15<CDE-15. Moreover, the study proved that daily supplementation of 50 mg/kg vitamin E is effective to ameliorate the hepatic OS status and metal disturbance in mice.
authors.affiliation: State Key Laboratory of Pollution Control and Resources Reuse, School of Environment, Nanjing University, Jiangsu, Nanjing, 210023, China.
authors.forename: Xuesheng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pollution Control and Resources Reuse, School of Environment, Nanjing University, Jiangsu, Nanjing, 210023, China.
authors.forename: Mingbao
authors.initials: M
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Pollution Control and Resources Reuse, School of Environment, Nanjing University, Jiangsu, Nanjing, 210023, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pollution Control and Resources Reuse, School of Environment, Nanjing University, Jiangsu, Nanjing, 210023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Pollution Control and Resources Reuse, School of Environment, Nanjing University, Jiangsu, Nanjing, 210023, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Qu
authors.affiliation: School of Environmental and Safety Engineering, Changzhou University, Jiangsu, Changzhou, 213164, China.
authors.forename: Dinglong
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pollution Control and Resources Reuse, School of Environment, Nanjing University, Jiangsu, Nanjing, 210023, China. wangzun315cn@163.com.
authors.forename: Zunyao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008670:Metals / Q000378:metabolism / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D055768:Halogenated Diphenyl Ethers; D008670:Metals; D014810:Vitamin E; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione