Differential proteome analysis of rat plasma after diisopropyl fluorophosphate (DFP) intoxication, a surrogate of nerve agent sarin.
Diisopropyl fluorophosphate (DFP), a surrogate of nerve agent sarin, is an organophosphorus (OP) compound which inhibits neuronal enzyme acetylcholinesterase (AChE). Exposure of this compound leads to a wide range of toxic symptoms and survivors may exhibit long term neurotoxicity related to cognitive and memory defects. Due to ease of availability and similar mechanism of action to other highly toxic nerve agent, DFP is widely used as model compound to trace changes associated with nerve agent exposures. Proximal fluids are widely used for the elucidation of biomarkers for exposure to toxic substances and to study the mechanism of toxicity. Using a rat model of OP intoxication, the present study was carried out to elucidate proteomic changes in plasma associated with DFP intoxication. Rats were exposed to a single dose (0.5 LD50) of DFP and their plasma proteome was studied, one day post exposure by two dimensional gel electrophoresis - mass spectrometry (2DE-MS). Some of the milestone changes were validated by Western blot analysis. A total 15 proteins showed significant fold changes in expression with respect to control after 1 day of DFP intoxication. Most of the proteins showing changes in expression at initial stages were related to immunogenic function, acute phase response, blood coagulation, and stress response. Experiments reported here demonstrate that 0.5 LD50 DFP intoxication leads to AChE inhibition, modulation of immunogenic function, and generation of stress at an early stage. Although, some proteins and their putative functional ramifications indicated similarity with those observed in our previous plasma proteome study, neurodegenerative changes were not observed in plasma of 0.5 LD50 DFP treated animals.
['Chaubey|Kalyani|K|', 'Alam|Syed Imteyaz|SI|', 'Waghmare|Chandra Kant|CK|', 'Singh|Lokendra|L|', 'Srivastava|Nalini|N|', 'Bhattacharya|Bijoy K|BK|']
D000818:Animals D001798:Blood Proteins D002800:Cholinesterase Inhibitors D002802:Cholinesterases D006706:Homeostasis D007279:Injections, Subcutaneous D007501:Iron D007531:Isoflurophate D008297:Male D000067397:Nerve Agents D020258:Neurotoxicity Syndromes D018384:Oxidative Stress D017208:Rats, Wistar D015203:Reproducibility of Results D012524:Sarin
DFP Nerve agents Plasma proteome Haptoglobin Organophosphates