Inhibition of human fetal brain acetylcholinesterase: Marker effect of neurotoxicity

Abstract

Human fetal brains were obtained after medical termination of pregnancy at 8-10 wk from informed patients. A definite regionalization of AChE was found in the brain of the fetus, with cerebellum recording the highest and cerebral hemisphere the lowest activity. Optimum conditions for the cerebellar AChE activity were determined with respect to molarity of the buffer, pH, temperature, and concentrations of substrate (acetylthiocholine iodide), activators (NaCl, MgCl2), and thiol indicator (dithiobisnitrobenzoic acid). In vitro inhibition of cerebellar AChE with two commercial pesticides, Metacid-50 (O,O-dimethyl p-nitrophenyl phosphorothioate) and carbaryl (N-methyl naphthyl-1-carbamate), were compared with pure anticholinesterase agents, diisopropylfluorophosphate (DFP) and physostigmine (eserine). In general, organophosphates are more neurotoxic than carbamate compounds, as evidenced by higher degree of AChE inhibition by DFP and Metacid-50 as compared to eserine and carbaryl. Assays were also done with psychotropic drugs by employing the procedure of in vitro AChE inhibition kinetics, and it was found that psychotropic drugs are less potent than organophosphate and carbamate compounds. Results indicate that pure and commercial organophosphates and carbamates and psychotropic drugs are all able to significantly alter the AChE activity. Thus exposure of the mother to these environmental toxicants may adversely affect the fetal neural functions.