4.5 Article

B-esterase determination and organophosphate insecticide inhibitory effects in JEG-3 trophoblasts

期刊

TOXICOLOGY IN VITRO
卷 32, 期 -, 页码 190-197

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2016.01.001

关键词

Organophosphate pesticides; Chlorpyrifos; Azinphos-methyl; Acetylcholinesterase; Carboxylesterase

资金

  1. Consejo Nacional de Investigaciones Cientificas y Tecnologicas [PIP 2009 0065]
  2. Agencia Nacional de Investigaciones Cientificas y Tecnicas (PICT) [1718]
  3. Universidad Nacional del Comahue [04-N021]
  4. Universidad Nacional del Comahue
  5. CONICET

向作者/读者索取更多资源

The placenta and trophoblasts express several B-esterases. This family includes acethylcholinesterase (AChE), carboxylesterase (CES) and butyrylcholinesterase (BChE), which are important targets of organophosphate insecticide (OP) toxicity. To better understand OP effects on trophoblasts, B-esterase basal activity and kinetic behavior were studied in JEG-3 choriocarcinoma cell cultures. Effects of the OP azinphos-methyl (Am) and chlorpyrifos (Cp) on cellular enzyme activity were also evaluated. JEG-3 cells showed measurable activity levels of AChE and CES, while BChE was undetected. Recorded Km for AChE and CES were 033 and 0.26 mM respectively. Native gel electrophoresis and RT-PCR analysis demonstrated CES1 and CES2 isoform expression. Cells exposed for 4 and 24 h to the OP Am or Cp, showed a differential CES and AChE inhibition profiles. Am inhibited CES and AChE at 4 h treatment while Cp showed the highest inhibition profile at 24 h. Interestingly, both insecticides differentially affected CES1 and CES2 activities. Results demonstrated that JEG-3 trophoblasts express AChE, CES1 and CES2. B-esterase enzymes were inhibited by in vitro OP exposure, indicating that JEG-3 cells metabolization capabilities include phase I enzymes, able to bioactivate OP. In addition, since CES enzymes are important for medicinal drug activation/deactivation, OP exposure may interfere with trophoblast CES metabolization, probably being relevant in a co-exposure scenario during pregnancy. (C) 2016 Published by Elsevier Ltd.

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