The combined effect of anticholinesterase compound DDVP and its antidote cholinesterase reactivator carboxim on implementation of cholinergic anti-inflammatory pathway

Abstract

Anticholinesterase compounds (оrganophosphate compounds– OPC, anticholinesterase drugs) are widely used in agriculture, various industries and households, in medicine. OPC can cause environmental pollution, as well as acute and chronic intoxications.1‒7 Cholinergic stimulation, as we established in 19872 and in subsequent studies, significantly reduces the mortality of white mice from sepsis caused by intraperitoneal or intrapulmonary administration, respectively of E. coli and P. vulgaris.3‒5,8 Thus, the cholinergic anti-inflammatory mechanism has been discovered in 1987,2 named «cholinergic antiinflammatory pathway» in 20029 after the research its implementation at the organismal, cellular and subcellular levels.3,4,9,10 It should be noted that in 1995 it was proved the possibility of cholinomimetics for emergency activation of antimicrobial resistance of the organism in sepsis.3,4 In the future, the study of the cholinergic anti-inflammatory pathway caused by the action of acetylcholine on α7n-acetylcholine receptors (α7nAChRs) cells of the monocyte-macrophage system (MMC), followed by inhibition of the production by the cells of proinflammatory cytokines (TNF-α, IL-1 β, IL-6) and reduced mortality from sepsis were devoted hundreds of articles various authors.5,9‒18 Reduced production of TNF-α, IL-1β, IL-6 (anti-inflammatory effect occurrence) for cholinergic anti-inflammatory pathway is provided kinase JAK2, transcription factor STAT3, NF-κB transcription factor).10,16‒18 The aim of the study was to evaluate the effect of acute intoxication of anticholinesterase compound in combination with its antidote cholinesterase reactivator carboxim on the mortality of mice from sepsis caused by experimental peritonitis (E. coli), and the concentration of pro-inflammatory cytokines TNFα, IL-1β and IL-6 in blood.