Assessment of the Endocrine-Disrupting Effects of Trichloroethylene and Its Metabolites Using in Vitro and in Silico Approaches

Abstract

Trichloroethylene (TCE) is a ubiquitous environmental contaminant, which may have effects on both ecosystem and human health. TCE has been reported to cause several toxic effects, but little effort has been made to assess the ecological risks of TCE or its major metabolites: trichloroethanol (TCOH), trichloroacetic acid, and oxalic acid (OA). In this study, the endocrine-disrupting potential of TCE and its metabolites were investigated using in vitro and in silico approaches. We examined alterations in the steroidogenesis pathway using the NCI-H295R cell line and utilized receptor-mediated luciferase reporter cell lines to identify effects on estrogen and androgen receptors. Molecular docking was also used to explore chemical interactions with these receptors. All test chemicals except OA significantly increased 17β-estradiol production which can be attributed to an up-regulation of 17β-hydroxysteroid dehydrogenase. Moreover, TCOH exhibited significant antiestrogenic activity with a RIC (20% relative inhibitory concentration) of 3.7 × 10 M. Molecular docking simulation supported this finding with lower docking scores for TCOH, indicating that hydrogen bonds may stabilize the interaction between TCOH and the estrogen receptor binding pocket. These findings suggest that TCE contamination poses an endocrine-disrupting threat, which has implications for both ecological and human health.

In Vitro characterization of the endocrine disrupting effects of per- and poly-fluoroalkyl substances (PFASs) on the human androgen receptor

“…This provides further evidence that some emerging PFASs are not as safe as previously thought and may have even greater potential to cause serious endocrine disrupting hazards than their legacy predecessors. In addition, it is important to note that apart from the direct inhibition at the hormone receptor, endocrine disruptors can elicit adverse health effects through different mechanisms such as disrupted steroidogenesis ( Rosenmai et al, 2016 ; La Merrill et al, 2020 ; Tachachartvanich et al, 2018 ). Further studies on the potential adverse effect of the emerging PFASs on steroidogenesis are warranted for more comprehensive hazard characterization.…”

Cytosolic Delivery of Proteins Using Amphiphilic Polymers with 2-Pyridinecarboxaldehyde Groups for Site-Selective Attachment

“…The protocol was modified from a previously described procedure. , Cells were trypsinized and diluted to a density of 50 000 cells/mL. An aliquot of 200 μL of cell stock was placed in a well of a 96-well plate (Corning) to reach a density of 10 000 cells/well.…”

Recent advances and trends of trichloroethylene biodegradation: A critical review

“…TCE is a ubiquitous environmental contaminant, which has adverse effects on both ecosystem and human health ( Tachachartvanich et al, 2018 ; Xiao et al, 2020 ). As a Group 1 carcinogen, TCE may increase the cancer risk of the kidney, cervix, liver and biliary passages, as well as non-Hodgkin lymphoma and esophageal adenocarcinoma ( Johnson et al, 1998 ; Wartenberg et al, 2000 ; Hansen et al, 2013 ; Vlaanderen et al, 2013 ; Siggins et al, 2021 ).…”

“…As a Group 1 carcinogen, TCE may increase the cancer risk of the kidney, cervix, liver and biliary passages, as well as non-Hodgkin lymphoma and esophageal adenocarcinoma ( Johnson et al, 1998 ; Wartenberg et al, 2000 ; Hansen et al, 2013 ; Vlaanderen et al, 2013 ; Siggins et al, 2021 ). In addition, TCE has been reported to cause endocrine disrupting effects ( Tachachartvanich et al, 2018 ). Concerns about the toxicity of TCE have driven its control.…”