دورية أكاديمية
Potentiation of antiseizure and neuroprotective efficacy of standard nerve agent treatment by addition of tariquidar.
| العنوان: | Potentiation of antiseizure and neuroprotective efficacy of standard nerve agent treatment by addition of tariquidar. |
|---|---|
| المؤلفون: | Meerhoff GF; Centre for Neuroscience, Swammerdam Institute of Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands., Vester SM; CBRN Protection, TNO Defense, Safety and Security, Rijswijk, PO Box 2280 AA, The Netherlands., Hesseling P; Centre for Neuroscience, Swammerdam Institute of Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands., Klaassen SD; CBRN Protection, TNO Defense, Safety and Security, Rijswijk, PO Box 2280 AA, The Netherlands., Cornelissen AS; CBRN Protection, TNO Defense, Safety and Security, Rijswijk, PO Box 2280 AA, The Netherlands., Lucassen PJ; Centre for Neuroscience, Swammerdam Institute of Life Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands., Joosen MJA; CBRN Protection, TNO Defense, Safety and Security, Rijswijk, PO Box 2280 AA, The Netherlands. Electronic address: Marloes.joosen@tno.nl. |
| المصدر: | Neurotoxicology [Neurotoxicology] 2018 Sep; Vol. 68, pp. 167-176. Date of Electronic Publication: 2018 Aug 18. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 7905589 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9711 (Electronic) Linking ISSN: 0161813X NLM ISO Abbreviation: Neurotoxicology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2001- : Amsterdam : Elsevier Science Original Publication: Park Forest South, Ill., Pathotox Publishers. |
| مواضيع طبية MeSH: | Anticonvulsants/*administration & dosage , Brain/*drug effects , Neuroprotective Agents/*administration & dosage , Quinolines/*administration & dosage , Seizures/*prevention & control, Animals ; Astrocytes/drug effects ; Atropine/administration & dosage ; Brain/physiopathology ; Cholinesterase Reactivators/administration & dosage ; Cholinesterases/metabolism ; Diazepam/administration & dosage ; Male ; Microglia/drug effects ; Neurons/drug effects ; Oximes/administration & dosage ; Pyridinium Compounds/administration & dosage ; Rats, Wistar ; Seizures/chemically induced ; Soman/toxicity |
| مستخلص: | Organophosphate (OP) induced seizures are commonly treated with anticholinergics, oximes and anticonvulsants. Inhibition of P-glycoprotein (PgP) has been shown to enhance the efficacy of nerve agent treatment in soman exposed rats. In the present study, the promising effects of the PgP inhibitor tariquidar were investigated in more detail in rats s.c. exposed to 150 μg/kg soman. Treatment with HI-6 and atropine sulfate (125 and 3 mg/kg i.m respectively) was administered 1 min after exposure. Diazepam (0.5 mg/kg i.m.) and/or tariquidar (7.5 mg/kg i.v.) were included either at 1 min or 40 min following onset of seizures. Animals that received tariquidar, in addition to HI-6 and atropine, at 1 min, displayed a rapid normalization of EEG activity and cessation of seizure-associated behaviour. This improvement by addition of tariquidar was even more substantial in animals that also received diazepam, either immediately or delayed. Animals exhibiting lower intensity seizures displayed less severe neuropathology (neuronal loss, microglia activation and astrogliosis), primarily in the piriform cortex, and to a lesser extent amygdala and entorhinal cortex. The present findings suggest that the interaction of tariquidar with atropine may be the decisive factor for enhanced treatment efficacy, given that atropine was previously found to be a PgP substrate. A more thorough understanding of the interactions of nerve agent antidotes, in particular the actions of central anticholinergics with benzodiazepines, could contribute to a future optimization of treatment combinations, particularly those aimed at later stage medical interventions. (Copyright © 2018 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Atropine; Diazepam; Oxime; Seizures; Soman; Tariquidar; p-Glycoprotein |
| المشرفين على المادة: | 0 (Anticonvulsants) 0 (Cholinesterase Reactivators) 0 (Neuroprotective Agents) 0 (Oximes) 0 (Pyridinium Compounds) 0 (Quinolines) 7C0697DR9I (Atropine) 96-64-0 (Soman) EC 3.1.1.8 (Cholinesterases) HUV88P6SJS (asoxime chloride) J58862DTVD (tariquidar) Q3JTX2Q7TU (Diazepam) |
| تواريخ الأحداث: | Date Created: 20180822 Date Completed: 20190321 Latest Revision: 20190321 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.neuro.2018.08.005 |
| PMID: | 30130561 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-9711 |
|---|---|
| DOI: | 10.1016/j.neuro.2018.08.005 |