Anticholinesterase Toxicity and Oxidative Stress
Anticholinesterase compounds, organophosphates (OPs) and carbamates (CMs) are commonly used for a variety of purposes in agriculture and in human and veterinary medicine. They exert their toxicity in mammalian system primarily by virtue of acetylcholinesterase (AChE) inhibition at the synapses and n...
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| Format: | Article |
| Language: | English |
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Wiley
2006-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/tsw.2006.38 |
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| author | Dejan Milatovic Ramesh C. Gupta Michael Aschner |
| author_facet | Dejan Milatovic Ramesh C. Gupta Michael Aschner |
| author_sort | Dejan Milatovic |
| collection | DOAJ |
| description | Anticholinesterase compounds, organophosphates (OPs) and carbamates (CMs) are commonly used for a variety of purposes in agriculture and in human and veterinary medicine. They exert their toxicity in mammalian system primarily by virtue of acetylcholinesterase (AChE) inhibition at the synapses and neuromuscular junctions, leading into the signs of hypercholinergic preponderance. However, the mechanism(s) involved in brain/muscle damage appear to be linked with alteration in antioxidant and the scavenging system leading to free radical-mediated injury. OPs and CMs cause excessive formation of F2-isoprostanes and F4-neuroprostanes, in vivo biomarkers of lipid peroxidation and generation of reactive oxygen species (ROS), and of citrulline, a marker of NO/NOS and reactive nitrogen species (RNS) generation. In addition, during the course of these excitatory processes and inhibition of AChE, a high rate of ATP consumption, coupled with the inhibition of oxidative phosphorylation, compromise the cell's ability to maintain its energy levels and excessive amounts of ROS and RNS may be generated. Pretreatment with N-methyl D-aspartate (NMDA) receptor antagonist memantine, in combination with atropine sulfate, provides significant protection against inhibition of AChE, increases of ROS/RNS, and depletion of high-energy phosphates induced by DFP/carbofuran. Similar antioxidative effects are observed with a spin trapping agent, phenyl-N-tert-butylnitrone (PBN) or chain breaking antioxidant vitamin E. This review describes the mechanisms involved in anticholinesterase-induced oxidative/nitrosative injury in target organs of OPs/CMs, and protection by various agents. |
| format | Article |
| id | doaj-art-30236045bab24773a190b692c8df48f8 |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2006-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-30236045bab24773a190b692c8df48f82025-02-03T01:26:16ZengWileyThe Scientific World Journal1537-744X2006-01-01629531010.1100/tsw.2006.38Anticholinesterase Toxicity and Oxidative StressDejan Milatovic0Ramesh C. Gupta1Michael Aschner2Department of Pediatrics, Medical School, Vanderbilt University, Nashville, TN, USAToxicology Department, Breathitt Veterinary Center, Murray State University, Hopkinsville, KY, USADepartment of Pediatrics, Medical School, Vanderbilt University, Nashville, TN, USAAnticholinesterase compounds, organophosphates (OPs) and carbamates (CMs) are commonly used for a variety of purposes in agriculture and in human and veterinary medicine. They exert their toxicity in mammalian system primarily by virtue of acetylcholinesterase (AChE) inhibition at the synapses and neuromuscular junctions, leading into the signs of hypercholinergic preponderance. However, the mechanism(s) involved in brain/muscle damage appear to be linked with alteration in antioxidant and the scavenging system leading to free radical-mediated injury. OPs and CMs cause excessive formation of F2-isoprostanes and F4-neuroprostanes, in vivo biomarkers of lipid peroxidation and generation of reactive oxygen species (ROS), and of citrulline, a marker of NO/NOS and reactive nitrogen species (RNS) generation. In addition, during the course of these excitatory processes and inhibition of AChE, a high rate of ATP consumption, coupled with the inhibition of oxidative phosphorylation, compromise the cell's ability to maintain its energy levels and excessive amounts of ROS and RNS may be generated. Pretreatment with N-methyl D-aspartate (NMDA) receptor antagonist memantine, in combination with atropine sulfate, provides significant protection against inhibition of AChE, increases of ROS/RNS, and depletion of high-energy phosphates induced by DFP/carbofuran. Similar antioxidative effects are observed with a spin trapping agent, phenyl-N-tert-butylnitrone (PBN) or chain breaking antioxidant vitamin E. This review describes the mechanisms involved in anticholinesterase-induced oxidative/nitrosative injury in target organs of OPs/CMs, and protection by various agents.http://dx.doi.org/10.1100/tsw.2006.38 |
| spellingShingle | Dejan Milatovic Ramesh C. Gupta Michael Aschner Anticholinesterase Toxicity and Oxidative Stress The Scientific World Journal |
| title | Anticholinesterase Toxicity and Oxidative Stress |
| title_full | Anticholinesterase Toxicity and Oxidative Stress |
| title_fullStr | Anticholinesterase Toxicity and Oxidative Stress |
| title_full_unstemmed | Anticholinesterase Toxicity and Oxidative Stress |
| title_short | Anticholinesterase Toxicity and Oxidative Stress |
| title_sort | anticholinesterase toxicity and oxidative stress |
| url | http://dx.doi.org/10.1100/tsw.2006.38 |
| work_keys_str_mv | AT dejanmilatovic anticholinesterasetoxicityandoxidativestress AT rameshcgupta anticholinesterasetoxicityandoxidativestress AT michaelaschner anticholinesterasetoxicityandoxidativestress |