In vitro inhibition of human red blood cell acetylcholinesterase (AChE) by temephos-oxidized products

Abstract

Temephos (Tem) is an organophosphorus pesticide widely used to kill and prevent the growth of the main vectors for the transmission of dengue, zika, and chikungunya viruses. In chlorinated water, Tem is oxidized to its dioxon-sulfoxide (Tem-dox-SO), dioxon-sulfone (Tem-dox-SO2), and sulfoxide (Tem-SO) derivatives; however, these compounds are not commercially available to be used as standards and in toxicological studies. In the present study, we synthesized and characterized the Tem-oxidation products and the compound 4,4′-sulfinyldiphenol. These compounds were obtained by a simple reaction between Tem or 4,4′-thiodiphenol with sodium hypochlorite or potassium periodate, and were characterized by IR, NMR, and UPLC-HRESIMS. The in vitro evaluation of inhibitory potency of Tem-oxidized products on human red blood cell acetylcholinesterase (RBC AChE) showed that Tem-dox-SO2 was the most potent inhibitor of human RBC AChE, and its effect was more pronounced than that observed for ethyl-paraoxon, a potent typical inhibitor of AChE. An HPLC-DAD method for the analysis of metabolic products of Tem was developed, which may be useful for monitoring in biological and environmental samples. The ability of Tem-oxidized metabolites to inhibit human RBC AChE suggests that the addition of Tem to chlorinated drinking water could result in an increase in the risk of RBC AChE inhibition after exposure.

Assessment of the genotoxic potential of temephos

“…The addition of temephos to drinking water has been reported to increase the risk of acetylcholinesterase inhibition in human red blood cells. High toxic potential of temephos was also reported (Verdin-Betancourt et al, 2019). The genotoxic and cytotoxic potential of temephos in human peripheral lymphocyte and hepatoma cells (HepG2) were evaluated using the CBMN and comet assays (Benitez-Trinidad et al, 2015).…”

“…So far, several studies have been conducted to assess temephos genotoxicity and cytotoxicity, using different cytogenetic assays. Some of these studies have reported that temephos might be genotoxic (Benitez-Trinidad et al, 2015;Verdin-Betancourt et al, 2019). The novelty of the current study is mainly related to its SCE data.…”

Human Biotransformation Pathway of Temephos Using an In Silico Approach

“…The WHO recommended temephos as a nonsystemic organophosphorus larvicide due to its low toxicity in mammals. Some studies indicate that temephos biotransformation is needed to produce toxic effects . Therefore, it is crucial to understand its biotransformation pathway in humans to identify metabolites formed and determine a possible toxicological hazard.…”

“…Temephos metabolites included in this study (Figure ) are a recompilation from rat metabolism, oxidized products formed in chlorinated water and in the environment, and possible metabolic products. ,,− Molecules were depicted in Avogadro, and their SMILES (simplified molecular input line entry system) codes were obtained using OpenBabel software. , SMILES is a chemical notation that allows the representation of chemical structures to be used in computational analysis. All predictions were determined with the same SMILES code (Table ).…”

“…However, another report suggested that temephos did not inhibit AChE enzymatic activity in humans that were exposed to 256 mg/person/day for five days or 64 mg/person/day for four weeks . Recently, we reported that temephos-oxidized derivatives are potent inhibitors of human AChE, and their potency is dependent on their grade of oxidation . Furthermore, some studies indicate that temephos is genotoxic and mutagenic and produces behavior alterations. − These results indicate that temephos metabolism is needed to produce its toxic effects, although its biotransformation has yet to be characterized.…”