Abstract
In this short review article, we list fresh questions regarding how metal ions are operating (or differently operating) in CNS compartments in the presence of concentrations of toxic organophosphonates (Nerve agents) [O = PR1R2R3]. Clearly, AChE active site serine residue phosphonylation is of primary and acute concern, but there may be a trigger for later onset (long ranging effects) events that may be acute and symptomatic but noncritical. Based on a biological inorganic chemistry approach, we have tried to position important questions herein starting from what is known in the primary literature, namely about zinc, iron, calcium, and magnesium ions.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
McDonough JH, Shih TM (1997) Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology. Neurosci Biobehav Rev 21:559–579, and references therein
Giacobini E (2004) Cholinesterase inhibitors: new roles and therapeutic alternatives. Pharmacol Res 50:433–440
Kuhl DE, Koeppe RA, Minoshima S, Snyder SE, Ficaro EP, Foster NL, Frey KA, Kilbourn MR (1999) In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease. Neurology 52:691–699
Weinstock M (1999) Selectivity of cholinesterase inhibition. CNS Drugs 12:307–323
“Organophosphate” and “brain” and “metals” (25 hits); “organophosphate” and “neuron” (169); “organophosphonate” and “neuron” (0). 1 reference was found containing all of the concepts “metal”, “brain” and “organophosphonate”. SciFinder Scholar. Accessed Dec 2011
Kim K, Tsay OG, Atwood DA, Churchill DG (2011) Destruction and detection of chemical warfare agents. Chem Rev 111:5345–5403
Augustinsson KB, Heimburger G (1955) Enzymatic hydrolysis of organophosphorus compounds. VI. Effect of metallic ions on the phosphorylphosphatases of human serum and swine kidney. Acta Chem Scand 9:383
Matsuda Y, Nagao M, Takatori T, Niijima H, Nakajima M, Iwase H, Kobayashi M, Iwadate K (1998) Detection of the sarin hydrolysis product in formalin-fixed brain tissues of victims of the Tokyo subway terrorist attack. Toxicol Appl Pharmacol 150:310–20
Bajgar J (2004) A organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem 38:151–216
Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321
Hirvonen MR, Paljärvi L, Naukkarinen A, Komulainen H, Savolainen KM (1990) Potentiation of malaoxon-induced convulsions by lithium: early neuronal injury, phosphoinositide signaling, and calcium. Toxicol Appl Pharmacol 104:276–289
Filbert M, Levine E, Ballough G (2005) Neuroprotection for nerve agent-induced brain damage by blocking delayed calcium overload: a review. J Med Chem Biol Radiol Def 3:1–21
Ballough GPH, Newmark J, Levine ES, Filbert MG (2008) Neuroprotection as a treatment for nerve agent survivors. In: Tuorinsky SD (ed) Medical aspects of chemical warfare, 1st edn. TMM publications, Washington, DC
Deshpande LS, Carter DS, Blair RE, DeLorenzo RJ (2010) Development of a prolonged calcium plateau in hippocampal neurons in rats surviving status epilepticus induced by the organophosphate diisopropylfluorophosphate. Toxicol Sci 116:623–631
Hamilton MG, Posavad C (1991) Alteration of calcium influx in rat cortical synaptosomes by soman. Neuroreport 2:273–276
Hu CY, Hsu CH, Robinson CP (1991) Effects of soman on calcium uptake in microsomes and mitochondria from rabbit aorta. J Appl Toxicol 11:293–296
Bandyopadhyay I, Kim MJ, Lee YS, Churchill DG (2006) Favorable pendant-amino metal chelation in VX nerve agent model systems. J Phys Chem A 110:3655–3661
Pazdernik TL, Emerson MR, Cross R, Nelson SR, Samson FE (2001) Soman-induced seizures: limbic activity, oxidative stress and neuroprotective proteins. J Appl Toxicol 21:s87–s94
Frederickson CJ (1989) Neurobiology of zinc and zinc-containing neurons. Int Rev Neurobiol 31:145–238
Acknowledgment
The Molecular Logic Gate Laboratory headed by D.G.C. was supported financially for this work by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2009–0070330 and 2010–0013660). We thank Officer Yoon Jeong Jang of the Chemical Defense Research Institute (Naegok-dong San 12-555, Seocho-gu, Seoul, Republic of Korea) for helpful discussions related to this research.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Wien
About this chapter
Cite this chapter
Tsay, O.G., Kim, K., Churchill, D.G. (2012). Metal ion roles and responses in the CNS under toxic organophosphonate exposure: traces of understanding and various open questions. In: Linert, W., Kozlowski, H. (eds) Metal Ions in Neurological Systems. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1001-0_14
Download citation
DOI: https://doi.org/10.1007/978-3-7091-1001-0_14
Published:
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-1000-3
Online ISBN: 978-3-7091-1001-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)