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 0.33 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.
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http://dx.doi.org/10.1016/j.tiv.2016.01.001 | DOI Listing |
Int J Pharm
January 2025
Drug Delivery and Disposition, KU Leuven, Gasthuisberg ON2, Herestraat 49 - box 921, 3000 Leuven, Belgium. Electronic address:
The widespread prevalence of colorectal cancer and its high mortality rate emphasize the urgent need for more effective therapies. When developing new drug products, a key aspect is ensuring that sufficiently high concentrations of the active drug are reached at the site of action. Drug transporters and drug-metabolizing enzymes can significantly influence the absorption and local accumulation of drugs in intestinal tissue.
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Department of Diagnostic & Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address:
Areca nut (AN) is a substance of abuse consumed by millions worldwide, in spite of established oral and systemic toxicities associated with its use. Previous research demonstrates methyl ester alkaloids in the AN, such as arecoline and guvacoline, exhibit mood-altering and toxicological effects. Nonetheless, their metabolism has not been fully elucidated in humans.
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Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan; Laboratory of Biochemistry and Molecular Biology, School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan; Laboratory of Functional Organoid for Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan; Global Center for Medical Engineering and Informatics, Osaka University, Osaka 565-0871, Japan; Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka 565-0871, Japan. Electronic address:
Caco-2 cells, a human colorectal adenocarcinoma cell line, are widely used to model small intestinal epithelial cells in the drug development process because they can predict drug absorption with high accuracy. However, Caco-2 cells have several issues. First, Caco-2 cells have little expression of cytochrome P450 3A4 (CYP3A4), which is a major drug-metabolizing enzyme in the human intestine.
View Article and Find Full Text PDFPlacenta
September 2024
Early Origins of Adult Health Research Group, Health and Biomedical Innovation, Clinical & Health Sciences, University of South Australia, Adelaide, SA, Australia. Electronic address:
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