Nakajima Akira, Saigusa Daisuke, Tetsu Naomi, Yamakuni Tohru, Tomioka Yoshihisa, Hishinuma Takanori
Laboratory of Pharmacotherapy, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Toxicol Lett. 2009 Aug 25;189(1):78-83. doi: 10.1016/j.toxlet.2009.05.003. Epub 2009 May 20.
Tetrabromobisphenol A (TBBPA) is widely used as a flame retardant and is suspected to be stable in the environment with possible widespread human exposures. In the present study, we investigated the behavioral effects of TBBPA and measured the levels of TBBPA in the brain after oral administration in mice. Acute treatment with TBBPA (5mg/kg body weight) 3h before the open-field test induced an increase in the horizontal movement activities. In contextual fear conditioning paradigm, mice treated with TBBPA (0.1mg/kg or 5mg/kg body weight) showed more freezing behavior than vehicle-treated mice. In addition, TBBPA (0.1mg/kg body weight) significantly increased the spontaneous alternation behavior in the Y-maze test. The levels of TBBPA in the brain following TBBPA treatment were determined by using LC/ESI-MS/MS system. In the brain regions examined, high amounts of TBBPA were detected in the striatum after treatment with 0.1mg/kg or 5mg/kg body weight TBBPA, whereas non-specific accumulation of TBBPA in the brain was found after treatment with 250 mg/kg body weight TBBPA. These results suggest that TBBPA accumulates in brain regions including the striatum and induces the behavioral alterations. Together, the possibility of widespread human exposure to TBBPA warrants further studies to characterize its neurotoxicity.
四溴双酚A(TBBPA)被广泛用作阻燃剂,并且被怀疑在环境中具有稳定性,可能会导致人类广泛接触。在本研究中,我们调查了TBBPA的行为效应,并测量了小鼠口服给药后大脑中TBBPA的水平。在旷场试验前3小时用TBBPA(5毫克/千克体重)进行急性处理,导致水平运动活动增加。在情境恐惧条件反射范式中,用TBBPA(0.1毫克/千克或5毫克/千克体重)处理的小鼠比用赋形剂处理的小鼠表现出更多的僵住行为。此外,TBBPA(0.1毫克/千克体重)在Y迷宫试验中显著增加了自发交替行为。通过使用液相色谱/电喷雾串联质谱系统测定TBBPA处理后大脑中TBBPA的水平。在用0.1毫克/千克或5毫克/千克体重的TBBPA处理后,在所检查的脑区中,纹状体中检测到大量的TBBPA,而在用250毫克/千克体重的TBBPA处理后,发现TBBPA在大脑中出现非特异性积累。这些结果表明,TBBPA在包括纹状体在内的脑区中积累并诱导行为改变。总之,人类广泛接触TBBPA的可能性值得进一步研究以表征其神经毒性。