Alterations in brain glutathione homeostasis induced by the nerve gas soman.
Public awareness of the dangers of chemical and biological warfare has been heightened in recent times. In particular, chemical nerve agents such as soman and its analogs have been developed and used in war as well as recent incidents, such as in Iraq and Japan. Soman, a rapid acting acetylcholinesterase inhibitor, produces a status epilepticus that leads to extensive neuropathology in vulnerable brain regions (eg, piriform cortex and hippocampus). This study was undertaken to determine whether oxidative mechanisms are involved in brain pathology during soman toxicity. Intracellular thiols such as glutathione (GSH) and protein sulfhydryls (PrSH) are among the most critical antioxidants used to combat oxidative stress. Here we report that during the seizure phase (1 h post soman exposure), PrSH levels in piriform cortex and hippocampus were decreased without changes in glutathione (GSH) levels. However, by 24 h post soman exposure (pathology phase), GSH levels were decreased by nearly 50% in the piriform cortex with a corresponding decrease in PrSH groups. The shift to a more oxidized thiol status indicates that oxygen free radicals likely participate in the neuropathology associated with soman-induced seizures.
Klaidman
Lori K
LK
University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 508, Los Angeles, CA 90089-9121, USA.
Adams
James D
JD
Cross
Robert
R
Pazdernik
Thomas L
TL
Samson
Fred
F
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002619:Chemical Warfare Agents / Q000494:pharmacology*; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000494:pharmacology*; D013226:Status Epilepticus / Q000139:chemically induced; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013997:Time Factors
D002619:Chemical Warfare Agents; D009419:Nerve Tissue Proteins; D013438:Sulfhydryl Compounds; D012999:Soman; D005978:Glutathione