Author/Editor		Milatović, D; Živin, M; Hustedt, E; Dettbarn, WD
Title		Spin trapping agent phenyl-N-tert-butylnitrone prevents diisopropylphosphorofluoridate-induced excitotoxicity in skeletal muscle of the rat
Type		članek
Source		Neurosci Lett
Vol. and No.		Letnik 278, št. 1-2
Publication year		2000
Volume		str. 25-8
Language		eng
Abstract		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.
Descriptors		ACETYLCHOLINESTERASE MUSCLE CONTRACTION NITROGEN OXIDES ISOFLUROPHATE FASCICULATION MUSCLE, SKELETAL SPIN LABELS REACTIVE OXYGEN SPECIES NECROSIS MUSCARINIC ANTAGONISTS FREE RADICAL SCAVENGERS EXCITATORY AMINO ACID AGONISTS CHOLINESTERASE INHIBITORS RATS, SPRAGUE-DAWLEY ATROPINE