Esmat Ahmed, El-Demerdash Ebtehal, El-Mesallamy Hala, Abdel-Naim Ashraf B
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Toxicol Lett. 2007 Jul 10;171(3):111-8. doi: 10.1016/j.toxlet.2007.05.001. Epub 2007 May 18.
Brain is a target organ for acrylonitrile (ACN) toxicity. The objective of the current work was to investigate ACN cytotoxicity in rat primary glial cells, using N-acetyl-l-cysteine (NAC) as a potential protective agent. Cells were exposed in vitro to different concentrations of ACN for different time intervals. Cell membrane integrity was assessed by trypan blue exclusion and lactate dehydrogenase (LDH) leakage. Approximately 50% membrane damage was observed in the incubations containing 1.0mM ACN for 3h. Therefore, these experimental conditions were used in subsequent studies. ACN enhanced lipid peroxidation, as indicated by malondialdehyde (MDA) accumulation, and depleted reduced glutathione (GSH) level with no change in total glutathione. Also, ACN was activated to cyanide (CN(-)) with dramatic decrease in ATP level. Cell treatment with NAC prior to exposure to ACN afforded some protection; as indicated by reducing MDA level and elevating level of both reduced and total glutathione. Further, pretreatment with NAC inhibited CN(-) formation and caused an increase in ATP level. Our results indicate that ACN is toxic to rat primary glial cells as evidenced by induction of oxidative stress and generation of CN(-) with subsequent energy depletion. NAC can play an important role against ACN-induced oxidative damage.
大脑是丙烯腈（ACN）毒性作用的靶器官。本研究的目的是使用N-乙酰-L-半胱氨酸（NAC）作为潜在的保护剂，研究ACN对大鼠原代神经胶质细胞的细胞毒性。将细胞在体外暴露于不同浓度的ACN中不同时间。通过台盼蓝排斥法和乳酸脱氢酶（LDH）泄漏评估细胞膜完整性。在含有1.0mM ACN孵育3小时的实验中观察到约50%的膜损伤。因此，这些实验条件用于后续研究。ACN增强脂质过氧化作用，表现为丙二醛（MDA）积累，并使还原型谷胱甘肽（GSH）水平降低，而总谷胱甘肽水平无变化。此外，ACN被激活生成氰化物（CN(-)），同时ATP水平显著下降。在暴露于ACN之前用NAC处理细胞可提供一定保护；表现为MDA水平降低以及还原型和总谷胱甘肽水平升高。此外，NAC预处理抑制了CN(-)的形成并使ATP水平升高。我们的结果表明，ACN对大鼠原代神经胶质细胞有毒性，表现为诱导氧化应激、生成CN(-)并随后导致能量消耗。NAC可在对抗ACN诱导的氧化损伤中发挥重要作用。
