Cholinesterases are enzymes able to hydrolyze the neurotransmitter acetylcholine and thus to terminate transmission. Once the enzymes are inhibited, excitotoxicity can appear in the adjacent cells. It is well known that oxidative stress is involved in the toxicity of cholinesterase inhibitors. Commonly, stress follows inhibition of cholinesterases and disappears shortly afterwards. In the present experiment, it was decided to test the impact of an inhibitor, neostigmine, on oxidative stress in BALB/c mice after a longer interval. The animals were sacrificed three days after onset of the experiment and spleens and livers were collected. Reduced glutathione (GSH), glutathione reductase (GR), glutathione S-transferase (GST), thiobarbituric acid reactive substances (TBARS), ferric reducing antioxidant power (FRAP), caspase-3 and activity of acetylcholinesterase (AChE) were assayed. The tested markers were not altered with exceptions of FRAP. The FRAP values indicate accumulation of low molecular weight antioxidants in the examined organs. The role of low molecular weight antioxidants in the toxicity of AChE inhibitors is discussed.

• Keywords
• excitotoxicita,
• MeSH
• Acetylcholinesterase MeSH
• Antioxidants MeSH
• Butyrylcholinesterase MeSH
• Cholinesterase Inhibitors * toxicity   MeSH
• Enzyme Assays MeSH
• Glutathione MeSH
• Homeostasis * drug effects   MeSH
• Liver enzymology   drug effects   MeSH
• Mice, Inbred BALB C MeSH
• Neostigmine toxicity   MeSH
• Oxidative Stress * drug effects   MeSH
• Spleen enzymology   drug effects   MeSH
• Research MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

The present experiment was aimed at assessing the application of neostigmine, an acetylcholinesterase (AChE) pseudo-irreversible inhibitor with poor penetration through the hematoencephalitic barrier, and the neurotransmitter acetylcholine (ACh). The experiment was done to evaluate their ability to modulate an infectious disease: tularemia. Mice infected with Franciselle tularensis and exposed to either ACh or neostigmine had a higher mortality and spleen bacterial burden when compared to infected mice exposed to saline solution only. The activated cholinergic anti-inflammatory pathway suppressed pathways necessary for tularemia resolution. Administration of AChE inhibitors to the individuals suffering from tularemia is contra-indicatory. Drugs based on AChE inhibition should be restricted when tularemia or disease with a similar pathogenesis is suspected.

• MeSH
• Acetylcholine * immunology   toxicity   MeSH
• Cytokines drug effects   MeSH
• Francisella tularensis pathogenicity   MeSH
• Immunomodulation MeSH
• Mice, Inbred BALB C MeSH
• Neostigmine * immunology   toxicity   MeSH
• Parasympathetic Nervous System drug effects   MeSH
• Tularemia * immunology   complications   mortality   MeSH
• Research MeSH
• Inflammation immunology   microbiology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH