title: Tris-(2,3-dibromopropyl) isocyanurate induces depression-like behaviors and neurotoxicity by oxidative damage and cell apoptosis in vitro and in vivo.
abstract: Tris-(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), an emerging brominated flame retardant, possesses the characteristics of candidate persistent organic pollutants and has displayed toxicity to fish and rodents. TDBP-TAZTO can pass through the blood-brain barrier and accumulate in the brain. TDBP-TAZTO might also induce neuronal cell toxicity. However, the neurotoxicity and mechanisms of TDBP-TAZTO have not yet been studied. We hypothesize that TDBP-TAZTO could induce neurotoxicity in mouse hippocampal neurons and SH-SY5Y cells. The mice were exposed to TDBP-TAZTO of 5 and 50 mg/kg by gavage, daily for 30 days. TDBP-TAZTO resulted in depression-like behaviors, which may be related with TDBP-TAZTO-induced upregulation of oxidative stress markers and overexpression of pro-apoptotic proteins in hippocampus. Furthermore, TDBP-TAZTO treatment for 48 hr (12.5, 25 and 50 µM) damaged SH-SY5Y cells, and led to cell apoptosis and oxidative stress in concentration-dependent manner. Our findings suggested that cell apoptosis and oxidative stress are important mechanisms in neurotoxicity induced by TDBP-TAZTO.
authors.affiliation: School of Public Health and Management, Binzhou Medical University, China.
authors.forename: Zhaoju
authors.initials: Z
authors.lastname: Dong
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Hu
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhu
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Mi
authors.forename: Wanglin
authors.initials: W
authors.lastname: Jiang
authors.forename: Xihou
authors.initials: X
authors.lastname: Hu
authors.forename: Liang
authors.initials: L
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001522:Behavior, Animal / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D003863:Depression / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005411:Flame Retardants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D014227:Triazines / Q000378:metabolism / Q000633:toxicity*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005411:Flame Retardants; D014227:Triazines; C541743:tris(2,3-dibromopropyl)isocyanurate