Milatovic D, Zivin M, Hustedt E, Dettbarn W D
Department of Pharmacology and Neurology, Vanderbilt University, School of Medicine, Nashville, TN 37212, USA.
Neurosci Lett. 2000 Jan 7;278(1-2):25-8. doi: 10.1016/s0304-3940(99)00904-0.
Indirect evidence suggests that reactive oxygen species (ROS) may mediate muscle fiber necrosis following muscle hyperactivity induced by the anticholinesterase diisopropylphosphorofluoridate (DFP). Pronounced muscle fasciculations and muscle fiber necrosis were seen when acetylcholinesterase (AChE) activity was reduced to less than 30% of control. The spin trapping agent phenyl-N-tert-butylnitrone (PBN) was used in vivo to directly assess the formation of ROS during DFP (1.75 mg/kg, s.c.) induced muscle hyperactivity. Pretreatment with PBN (300 mg/kg, i.p.), the concentration necessary for in vivo spin trapping, prevented muscle hyperactivity as well as necrosis and attenuated the DFP induced AChE inhibition otherwise seen in DFP only treated rats. PBN had no effect when given after fasciculations were established. Muscle extracts from PBN and DFP treated rats subjected to electron spin resonance (ESR) spectroscopy tested negative for ROS. While the role of PBN as an antioxidant is well established, its prophylactic effect against excitotoxity induced by an AChE inhibitor are due to its protection of AChE, an unexpected non-antioxidant action.
间接证据表明，活性氧（ROS）可能在抗胆碱酯酶二异丙基氟磷酸酯（DFP）诱导的肌肉活动亢进后介导肌纤维坏死。当乙酰胆碱酯酶（AChE）活性降低至对照的30%以下时，可见明显的肌肉束颤和肌纤维坏死。自旋捕获剂苯基-N-叔丁基硝酮（PBN）在体内用于直接评估DFP（1.75 mg/kg，皮下注射）诱导的肌肉活动亢进期间ROS的形成。用PBN（300 mg/kg，腹腔注射）进行预处理（体内自旋捕获所需的浓度）可预防肌肉活动亢进以及坏死，并减弱DFP诱导的AChE抑制作用，而在仅用DFP处理的大鼠中会出现这种抑制作用。在束颤形成后给予PBN则没有效果。对接受电子自旋共振（ESR）光谱检测的PBN和DFP处理大鼠的肌肉提取物进行检测，结果显示ROS呈阴性。虽然PBN作为抗氧化剂的作用已得到充分证实，但其对AChE抑制剂诱导的兴奋性毒性的预防作用归因于其对AChE的保护，这是一种意想不到的非抗氧化作用。
