Podratz Jewel L, Windebank Anthony J
Program in Molecular Neuroscience, Mayo Graduate School, Rochester, MN, USA.
Neurotoxicology. 2005 Jun;26(3):343-50. doi: 10.1016/j.neuro.2005.01.003.
Using dorsal root ganglion neurons (DRG), in vitro, we studied the effects of nerve growth factor (NGF) on a toxin extracted from ethylene oxide (EO) sterilized hemodialyzers. Tissue culture medium passed through dialyzers produced beading of DRG axons that was inhibited by increasing the concentration of NGF from 3.5 to 10 ng/ml. The antioxidant enzymes, catalase and glutathione peroxidase (GPx), prevented neurite beading while superoxide dismutase (SOD) alone did not. 3-amino-1,2,4-triazole (Az), an inhibitor of catalase blocked the protective effects of catalase and NGF. 1,3 bis[chloromethyl]-1-nitrosourea (BCNU) inhibits glutathione reductase, and reduces intracellular glutathione levels; it blocked the protective effects of NGF. Dialyzer treated medium was found to have increased peroxide content. In parallel experiments, NGF protected DRG neurons from hydrogen peroxide (H(2)O(2)) toxicity that was inhibited by Az and BCNU. NGF was also shown to upregulate glutathione in DRG neurons. We propose that EO gas used in the sterilization of hemodialyzers is responsible for the neurotoxicity and is most likely due to oxidative damage in DRG neurons. NGF protects DRG from this toxin by upregulating antioxidants such as catalase, GPx and GSH.
我们在体外使用背根神经节神经元（DRG），研究了神经生长因子（NGF）对从环氧乙烷（EO）灭菌血液透析器中提取的一种毒素的影响。通过透析器的组织培养基导致DRG轴突发芽，而将NGF浓度从3.5 ng/ml提高到10 ng/ml可抑制这种现象。抗氧化酶过氧化氢酶和谷胱甘肽过氧化物酶（GPx）可防止神经突形成串珠，而单独的超氧化物歧化酶（SOD）则不能。过氧化氢酶抑制剂3-氨基-1,2,4-三唑（Az）可阻断过氧化氢酶和NGF的保护作用。1,3-双[氯甲基]-1-亚硝基脲（BCNU）抑制谷胱甘肽还原酶并降低细胞内谷胱甘肽水平；它阻断了NGF的保护作用。发现经透析器处理的培养基中过氧化物含量增加。在平行实验中，NGF保护DRG神经元免受过氧化氢（H₂O₂）毒性的影响，而Az和BCNU可抑制这种保护作用。还发现NGF可上调DRG神经元中的谷胱甘肽。我们认为，用于血液透析器灭菌的EO气体是神经毒性的原因，很可能是由于DRG神经元中的氧化损伤。NGF通过上调过氧化氢酶、GPx和谷胱甘肽等抗氧化剂来保护DRG免受这种毒素的侵害。
