Study On The Mice Neurotoxicity Of Butyl Benzyl Phthalate In Vivo And In Vitro

It was found that BBP (Butyl benzyl phthalate) had some toxicity on reproduction, developmention, oxidative damage and endocrine. Nevertheless, it is still lack of studies about neurovirulence on animals and human, what is more, the mechanism of action is still need move forward a single step exploration.In the study, cell viability, nerve cytotoxicity test, apoptosis function in vitro combined with the whole animal behavior assays, chitinase activity and microscopic fluorescent technology in vivo to evaluate BBP’s neurotoxicity. This study made a parallel comparison among BBP, DBP and their common metabolite MBP to explore toxic effect of them. Preliminary discussion of BBP’s influence on memory and learning of mice and the potential mechanism of BBP through brain tissue section analysis and the change of neurotransmitter.The study in vitro to evaluate BBP’s cytotoxicity by MTT assay and Hoechst33258staining and to evaluate BBP’s oxidative damage to N2a cells by ROS, MDA and GSH content detection. Use a series concentration of BBP, DBP and MBP at0.04g/L,2g/L and10g/L to contaminate N2a cells, parallel comparison them by detect ROS, MDA and GSH content.In vivo, use a series concentration gradient BBP of0(the control group)、50、250、1250mg/kg in vivo test by gavage administration last for two weeks. Through a train of classical behavioral experiment such as Morris water maze, tail suspension, forced swimming test and so on. Statistic analysis of swimming track and the time spend in different quadrant, reflect the influence of memory and learning of mice by BBP. Measure oxidative damage levels of brain, liver and kidney respectively. To detect the potential molecular mechanism of BBP’s toxicity,5-hydroxytryptamine and p-CREB of left brain were measured.The results show that BBP have some damages on cells and tissues. On the basis of hippocampus tissue sections displayed that hippocampus cells became more and more incomplete as the increase of BBP exposure concentration. Cells emerged apoptosis in the hippocampus at the highest BBP exposure group (1,250mg/kg) and hippocampal CAland DG region come up with the spatial learning and memory impairment, about1/3dorsal hippocampus cells that control the mice spatial learning and memory was damnified. BBP exposure cause the decrease of neurotransmitters, which then in turn down regulated the levels of CREB phosphorylation by the cAMP/protein kinase A (PKA) mediated signaling. Thus attenuate the effects of CREB downstream and the impaired behavioral performance were appeared.