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.

Effect of long term Treatment of Chlorpromazine and Diazepam on the activity of acetyl cholinesterase in the chicks’ blood

“…While chronic diazepam treatment at 30 mg/kg/day caused only a slight but non significant increase in both plasma and RBC enzyme activity which was about 9% and 13% respectively of the control group . Estimation of acetyl cholinesterase activity is of importance in studies concerning enzyme synthesis mechanisms (10)(11)(12). In the present study, we found that long-term administration of chlorpromazine increased blood Ache activity.…”

Sources of exposure to and public health implications of organophosphate pesticides

“…All four children also suffered from mental and growth retardation. Maternal exposure to organophosphates is likely to affect the acetylcholinesterase present in fetal brains as well as the fetal neural function (68). Organophosphate exposure in fetuses, neonates, and infants is an area of developmental toxicology that requires further research.…”

Withdrawal effect of Chlorpromazine and Diazepam on chick blood (Plasma, Red Blood Cell) Acetyl cholinesterase activity

“…Acetyl cholinesterase (AChE) is a membrane bound enzyme found in different tissues and play a important role for regulation of most physiological event, involving the turnover of acetylcholine (1)(2)(3). The activity of blood and/or 'true' AChE have been found to be affected by a number of antipsychotic drugs (1,(4)(5)(6)(7)(8)(9).Chronic treatment of rat and/or chicks with chlorpromazine and diazepam resulted increase in AChE activity (4,5). Similar finding were obtained from enzyme assay of chick and rabbit brain and cerebrospinal fluid (10).The effect by chlorpromazine in true AChE activity appear to be reversible (1), depending on the duration of drug administration (11).…”