Neurotoxicity and pattern of acetylcholinesterase inhibition in the brain regions of rat by bromophos and ethylbromophos.
Bromophos (Bp) and ethylbromophos (EBp) are two structurally homologous organophosphorus (OP) insecticides which show wide differences in their toxicity as well as neurotoxic symptoms in the laboratory rat. EBp is 24-fold more toxic (LD50 = 91 +/- 14 mg/kg body wt) than Bp (LD50 = 2218 +/- 195 mg/kg body wt) and only EBp produced characteristic tremors and lacrimation. In vivo cholinesterase inhibition was in the order plasma > erythrocytes > brain. Experiments with equitoxic and equimolar doses showed that EBp is a more potent anticholinesterase compound than Bp. Since IC50 values for the brain AChE were similar for both OPs, the target enzyme sensitivity was not a major factor in their differential toxicity. In vitro reactivation of serum ChE was significantly higher in the case of EBp than that of Bp. AChE in the brain regions showed differential inhibition in vivo. The brain stem AChE inhibition was least by Bp, whereas it was highest in the case of EBp. Both the OPs produced high AChE inhibition in the hippocampus. Differential inhibition of AChE in the brain regions and its consequent effects may be important factors in the differential neurotoxicity of OPs.
Santhoshkumar
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P
Infestation Control and Protectants Department, Central Food Technological Research Institute, Mysore, India.
Karanth
S
S
Shivanandappa
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T
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D007928:Lethal Dose 50; D010755:Organophosphates / Q000633:toxicity; D063086:Organothiophosphates / Q000633:toxicity*; D051381:Rats
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D010755:Organophosphates; D063086:Organothiophosphates; C041062:ethyl bromophos; C100092:bromophos