Yousefpour M, Bahrami F, Shahsavan Behboodi B, Khoshbaten A, Asgari A
Research Center for Chemical Injuries, Baqiyatallah University of Medical Science, Tehran, Iran.
Toxicology. 2006 Jan 16;217(2-3):221-7. doi: 10.1016/j.tox.2005.09.018. Epub 2005 Nov 10.
Organophosphates (OPs) neurotoxicity is attributed both to their well-known cholinergic and recently attended non-cholinergic effects. Since parathion has been observed to be responsible for more cases of poisoning than any other OP insecticides, it is vitally important to investigate other mechanisms, besides cholinesterase inhibition, which can potentially contribute to the neurotoxicity of parathion (or its metabolite, paraoxon). In present study, hippocampal cells obtained from Wistar rat neonates were cultured in neurobasal medium supplemented with B27 serum where different doses of paraoxon were also introduced. The neuronal growth in the control group and those exposed to paraoxon was compared. Phase contrast microscopy, cell staining (Neutral Red) and computer assessment morphometric study (Motic) were used to study cell morphology, viability and type of cell death. Statistical analysis was carried out using one-way ANOVA. There was no clear morphologic differences between neurons in the control group and those exposed to 10 microM paraoxon; however, deformity of the soma was clear in pellets containing higher concentration of paraoxon. Ultrastructure of cells was markedly altered at 50 microM dose of paraoxon as evidenced by gradual discontinuation of cytoplasm, appearing of numerous vacuoles and intracytoplasmic myelin figure. The processes (neurites) did not grow in media containing 100 microM paraoxon or more. Viability decreased with increasing paraoxon especially above 100 microM. In conclusion, the present data reveal that paraoxon, in 30 microM or higher concentrations, induces a decrease in cell growth, followed by cell swelling and neuronal death (possibly necrosis).
有机磷酸酯(OPs)的神经毒性既归因于其众所周知的胆碱能效应,也归因于最近受到关注的非胆碱能效应。由于观察到对硫磷导致的中毒病例比任何其他OP类杀虫剂都多,因此研究除抑制胆碱酯酶之外的其他可能导致对硫磷(或其代谢产物对氧磷)神经毒性的机制至关重要。在本研究中,从Wistar大鼠新生幼崽获取的海马细胞在添加了B27血清的神经基础培养基中培养,同时也加入了不同剂量的对氧磷。比较了对照组和暴露于对氧磷的细胞组的神经元生长情况。使用相差显微镜、细胞染色(中性红)和计算机辅助形态计量学研究(Motic)来研究细胞形态、活力和细胞死亡类型。采用单因素方差分析进行统计分析。对照组神经元与暴露于10微摩尔对氧磷的神经元之间没有明显的形态学差异;然而,在含有较高浓度对氧磷的细胞团中,细胞体出现了明显的畸形。在50微摩尔对氧磷剂量下,细胞超微结构明显改变,表现为细胞质逐渐中断、出现大量空泡和胞浆内髓鞘样结构。在含有100微摩尔及以上对氧磷的培养基中,神经突不生长。随着对氧磷浓度增加,细胞活力下降,尤其是在100微摩尔以上。总之,目前的数据表明,30微摩尔及以上浓度的对氧磷会导致细胞生长减少,随后细胞肿胀和神经元死亡(可能为坏死)。