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Investigation of mice blood neuropathy target esterase as biochemical marker of exposure to neuropathic organophosphorus compoundsстатья
- Авторы: Rudakova E.V., Sigolaeva L.V., Makhaeva G.F.
- Сборник: Toxicological Problems
- Глава в коллективной монографии
- Год издания: 2014
- Место издания: Military Publishing House Sofia, Bulgaria
- Первая страница: 39
- Последняя страница: 50
- Аннотация: A hen is a standard animal model for studying organophosphate-induced delayed neurotoxicity (OPIDN). Recently we developed a mouse biochemical model for organophosphorus compounds (OPC) neuropathic potential assessment based on brain neuropathy target esterase (NTE) and acetylcholinesterase (AChE) assay. The aim of the present study was to investigate the possibility of using the whole blood mice NTE as a biochemical marker for exposure to neuropathic OPCs and the possibility of OPIDN risk assessment in exposed species by comparison of blood NTE and AChE inhibition. Given that NTE and AChE inhibition in brain is a biomarker of OPIDN and acute cholinergic toxicity, respectively, we compared the NTE and AChE inhibition in whole blood and in brain of mice 1 h after a single i.p administration of increasing doses of two neuropathic OPCs possessing different acute toxicity: the toxic (C3H7O)2P(O)OCH=CCl2 (PrDChVP) and the low toxic (C4H9O)2P(O)OCH(CF3)2 (diBu-PFP). For measuring blood NTE activity a highly sensitive tyrosinase LBL biosensor was used. We showed that both OPCs inhibited AChE and NTE in mice blood and brain in dose-dependent manner. The corresponding values of ED50 were calculated. A strong correlation was found between inhibition of brain and blood NTE: r = 0.994 for PrDChVP and 0.997 for diBu-PFP, as well as between brain and blood AChE inhibition: r = 0.999 for PrDChVP and 0.969 for diBu-PFP. For both OPCs the ratio ED50(AChE)/ED50( NTE) in blood was shown to corresponds to that in brain, i.e., the ratio between NTE and AChE inhibition, measured in blood, may be used to characterize the probability of OPIDN development versus acute cholinergic toxicity. The results allow us to consider mice blood NTE as a biochemical marker of exposure to neuropathic OPCs.Inhibition of NTE in blood can be used in conjunction with inhibition of blood AChE to assess the likelihood that an exposure to OPC would produce cholinergic and/or delayed neuropathic effects.
- Добавил в систему: Сиголаева Лариса Викторовна