title: Combined in silico and in vivo studies shed insights into the acute acetylcholinesterase response in rat and human brain.
abstract: Combined in vivo and in silico studies were undertaken to gain insights into the change in mammalian brain acetylcholinesterase (AChE) activity under acute toxicity conditions in response to two representatives of organophosphates (OPs)--dichlorvos (DCV) and dimethoate (DM). In vivo experiments elucidated that DCV, at multiple sublethal doses for acute time periods, markedly reduced (10-25%) AChE activity, whereas with DM intoxication, a decrease in enzyme activity appeared to be lower, that is, (2-15%), in contrast to respective normal control (100%). Furthermore, a significant inhibition (P < 0.01) in the brain esterase activity was recorded for positive control animals treated with an alkylating agent-cyclophosphamide, with spontaneous reactivation at later time periods. In vivo results were further substantiated with in silico molecular docking analysis using "Autodock 4.2." The lowest binding energy obtained through the computational study strongly augment that DCV binds to brain AChE with greater affinity compared with DM with reference to ∆G and Ki values. Thus, the animal biochemical assay and computational assessment suggest that DM is better to be used over DCV. The precautionary antidote for exposed humans can be developed prior to dealing with OPs. The study will aid in efficacious and safe clinical use of the above-mentioned compounds.
authors.affiliation: Division of Genetics, Department of Zoology, Gene-Tox Laboratory, Aligarh Muslim University, Aligarh, U.P., India.
authors.forename: Nazia
authors.initials: N
authors.lastname: Nazam
authors.affiliation: Department of Biosciences, Integral University, Lucknow, U.P., India.
authors.forename: Sibhghatulla
authors.initials: S
authors.lastname: Shaikh
authors.affiliation: Division of Genetics, Department of Zoology, Gene-Tox Laboratory, Aligarh Muslim University, Aligarh, U.P., India.
authors.forename: Mohammad Iqbal
authors.initials: MI
authors.lastname: Lone
authors.affiliation: Division of Genetics, Department of Zoology, Gene-Tox Laboratory, Aligarh Muslim University, Aligarh, U.P., India.
authors.forename: Monika
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Division of Genetics, Department of Zoology, Gene-Tox Laboratory, Aligarh Muslim University, Aligarh, U.P., India.
authors.forename: Waseem
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D003198:Computer Simulation; D004006:Dichlorvos / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004117:Dimethoate / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008297:Male; D062105:Molecular Docking Simulation; D051381:Rats
chemical_list: D004006:Dichlorvos; D000110:Acetylcholinesterase; D004117:Dimethoate
keywords: Autodock 4.2; acetylcholinesterase; cyclophosphamide; dichlorvos; dimethoate