邻苯二甲酸丁基苄酯致神经细胞氧化损伤Neurotoxicity and the Oxidative Damage Induced by Butyl Benzyl Phthalate
闵安娜;刘锋明;晏彪;陈明清;杨旭;
摘要(Abstract):
为探究邻苯二甲酸丁基苄酯(butyl benzyl phthalate,BBP)对小鼠神经的毒性作用,进行了小鼠体外毒理学研究。首先用不同浓度的邻苯二甲酸丁基苄酯染毒神经模型细胞—N2a神经瘤细胞,通过噻唑蓝比色法(MTT),Hoechst 33258染色实验评价邻苯二甲酸丁基苄酯的细胞毒效应;通过对染毒细胞氧自由基(ROS)、丙二醛(MDA)、还原型谷胱甘肽(GSH)含量的检测来探究BBP对小鼠神经瘤细胞的氧化损伤效应。随着BBP浓度的不断增高,细胞的MTT值逐渐变小,当BBP的浓度达到10 g·L-1时,MTT实验结果与对照组出现显著性差异;Hoechst 33258染色结果显示:高浓度的BBP导致细胞核呈现出不规则状态,出现了凋亡小体;随着BBP染毒浓度的升高N2a细胞中的ROS水平和MDA含量逐渐上升,分别在0.16 g·L-1和10 g·L-1开始与对照组相比出现了显著性的差异(p<0.05);而GSH系数呈现下降趋势,在0.32 g·L-1时开始出现显著性差异(p<0.05)。实验结果表明高浓度的邻苯二甲酸丁基苄酯可以导致神经瘤细胞的凋亡,并产生氧化损伤效应。
关键词(KeyWords): 邻苯二甲酸丁基苄酯;细胞凋亡;细胞毒性;氧化损伤;神经毒性
基金项目(Foundation): 国家科技支撑计划项目(2012BAJ02B003);; 国家自然科学基金重点项目(51136002)
作者(Author): 闵安娜;刘锋明;晏彪;陈明清;杨旭;
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DOI:
参考文献(References):
- [1]Wezel A P,Vlaardingen V,Posthumus R,et al.Environmental risk limits for two phthalates,with special emphasis on endocrine disruptive properties[J].Ecotoxicology and Environmental Safety,2000,46(3):305-321
- [2]张锡辉.高等环境化学与微生物学原理及应用口咽[M].北京:化学工业出版社,2001:147-149
- [3]Cantreeds W.Comparision between the organic fraction of suspended matter at a background and an urban station[J].Science of the Total Environment,1997,8(1):79-88
- [4]莫测辉,蔡全英,吴启堂,等.我国城市污泥中邻苯二甲酸酯的研究[J].中国环境科学,2001,21(4):362-366
- [5]MikμLa P,SvobodováZ,SmutnáM.Phthalates:Toxicology and food safety-a review[J].Czech Journal of Food,2005,23(6):217-223
- [6]刘慧杰,舒为群.邻苯二甲酸酯类化合物的毒理学效应及对人类健康的危害[J].第三军医大学学报,2004,26(19):1778-1781
- [7]Swan S H.Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans[J].Environmental Research,2008,108(2):177-184
- [8]Lyche J L,Gutleb A C,Bergman A,et al.Reproductive and developmental toxicity of phthalates[J].Journal of Toxicology and Environmental Health,Part B:Critical Reviews,2009,12(4):225-249
- [9]Minoru K.Toxicity of butylbenzyl phthalate(BBP)and other phthalate esters to nervous tissue in cμLture[J].Toxicology Letters,1980,6(6):373-378
- [10]杨波,李文兰.邻苯二甲酸丁基苄酯对雄性大鼠生殖系统影响[J].哈尔滨商业大学学报(自然科学版),2006,(5):11-13
- [11]Tanida T,Warita K,Ishihara K,et al.Fetal and neonatal exposure to three typical environmental chemicals with different mechanisms of action:Mixed exposure to phenol,phthalate,and dioxin cancels the effects of sole exposure on mouse midbrain dopaminergic nuclei[J].Toxicology Letters,2009,189(1):40-47
- [12]聂金雷,时庆德,张勇,等.利用荧光探针直接测定线粒体活性氧的形成[J].中国应用生理学杂志,2002,18(2):196-198
- [13]Tandon V,Gupta R K.Effect of Vitex negundo on oxidative stress[J].Indian Journal of Pharmacology,2005,37(1):38-40
- [14]张志良.植物生理学实验指导(第二版)[M].北京:北京高等教育出版社,1990
- [15]马萍,杜娟,罗清,等.纳米Fe3O4对小鼠肺细胞的氧化损伤[J].生态毒理学报,2012,7(1):44-48
- [16]Ma P,Du J,Luo Q,et al.Fe3O4nanoparticles to the oxidative damage of rats'pneumonocyte[J].Asian Journal of Ecotoxicology,2012,7(1):44-48(in Chinese)
- [17]Seo K W,Kim K B,Kim Y J,et al.Comparison of oxidative stress and changes of xenobiotic metabolizing enzymes induced by phthalates in rats[J].Food and Chemical Toxicology,2004,42(1):107-114
- [18]McIntyre B S,Barlow N J,Wallace D G,et al.Effects of in utero exposure to linuron on androgen-dependent reproductive development in the male Crl:CD(SD)BR rat[J].Toxicology and Applied Pharmacology,2000,167(2):87-99
- [19]Schanbacher B D,Ewing L L.Simultaneous determination of testosterone,α-androstan-17β-ol-3-one,5α-androstane-3alpha,17β-diol and 5α-androstane-3β,17β-diol in plasma of adult male rabbits by radioimmunoassay[J].Endocrinology,1975,97(4):787-792
- [20]Parks LG,Ostby J S,Lambright C R,et al.The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat[J].Toxicological Sciences,2000,58(2):339-349
- [21]McIntyre B S,Barlow N J,Sar M,et al.Effects of in utero linuron exposure on rat Wolffian an duct development[J].Reproductive Toxicology,2002,16(2):131-139
- [22]Gray L E,Ostby J,Furr J,et al.Perinatal exposure to the phthalates DEHP,BBP,and DINP,but not DEP,DMP,or DOTP,alters sexual differentiation of the male rat[J].Toxicological Sciences,2000,58(2):350-365
- [23]Wormuth M,Scheringer M,Vollenweider M,et al.What are the sources of exposure to eight frequently used phthalic acid esters in Europeans[J].Risk Analysis,2008,6(2):803-824
- [24]王婧,蔡凤云,曾强,等.邻苯二甲酸丁基苄酯致大鼠肺细胞氧化损伤作用的体外研究[J].医学研究杂志,16-18
- [25]李文兰,季宇彬,姜安玺,等.环境激素邻苯二甲酸丁基苄酯在动物脏器中的代谢[J].哈尔滨工业大学学报,2005(12):1674-1677