AhR Agonist Activity Confirmation of Polyhalogenated Carbazoles (PHCZs) Using an Integration of in Vitro, in Vivo, and in Silico Models

Abstract

Polyhalogenated carbazoles (PHCZs) are a kind of rising environmental pollutant that has been reported to pose high risk to human beings and the natural environment. PHCZs are of a similar molecular structure with of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and exhibited some dioxin-like toxicity. Dioxin-like compounds (DLCs) are banned by the Stockholm Convention due to their potential adverse impacts to the environment and public health. However, a few efforts have been made toward the regulation of PHCZs. Herein, we initiated multimodels to systematically determine and validate the dioxin-like effects of PHCZs on a large scale. Transgenic zebrafish line-Tg(cyp1a-12DRE:EGFP) and stably transfected HepG2 cell line with luciferase reporter plasmids were used to screen and evaluate the aryl hydrocarbon receptor (AhR) agonist effects of the target PHCZs, which were then verified by application of molecular docking and expression levels of AhR downstream genes. Results of the two bioassays showed that most of the tested PHCZs could pose dioxin-like AhR agonist effects, change the expression levels of AhR downstream genes, and interact with AhR in accordance with TCDD. In summary, data presented here can help to guide the safe use and regulation of PHCZs.

Stage Dependent Enantioselective Metabolism of Bifenthrin in Embryos of Zebrafish (Danio rerio) and Japanese Medaka (Oryzias latipes)

“…Zebrafish (Danio rerio) husbandry and management were performed according to our previous study. 42 Adult wild-type zebrafish (strain 5D) were maintained under a 14:10-h light:dark cycle within a 242-tank recirculating system (Aquaneering Inc., U.S.A.) containing conditioned reverse osmosis water. Adult zebrafish were kept directly onsystem using in-tank breeding traps suspended within 3-L tanks and fed with ad libitum twice a day with GEMMA Micro 300 diet (Skretting, U.S.A.).…”

“…Zebrafish ( Danio rerio ) husbandry and management were performed according to our previous study . Adult wild-type zebrafish (strain 5D) were maintained under a 14:10-h light:dark cycle within a 242-tank recirculating system (Aquaneering Inc., U.S.A.) containing conditioned reverse osmosis water.…”

Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles

“…MeP and MeP-NPs were added in triplets in the concentration range 0.125-100 µM (according to the MeP concentration) and incubated for 2 h. To determine cytotoxicity, cells were treated with AA alone or in combination with MeP in a molar ratio of 1:20 to MeP and then incubated for 72 h [83]. Cell survival was determined using the standard MTT assay [110]. Cell viability was determined as the percent of untreated control.…”

Analysis of the Different Metabolic Phenotypes of Metalaxyl Enantiomers in Adolescent Rat by Using 1H NMR Based Urinary Metabolomics

“…Even, the changes in gut microbiota could be reflected in urine. 23 In this study, we want to use the NMR-based urinary metabolomics to find the changes of metabolic phenotypes in adolescent rats, which were exposed in the low concentration of R-metalaxyl and Smetalaxyl. These results could provide more explanation of the metabolic and toxic effects of different metalaxyl enantiomers in the growing stage of rats.…”

“…Compared with the serum, urine is a noninvasive sampling, and the analysis has been detailed earlier. , Nowadays, urine is often used for metabolic profiling and relevant biomarker screening. , The metabolic phenotype of urine could reveal the metabolic changes of vital movement. Even, the changes in gut microbiota could be reflected in urine . In this study, we want to use the NMR-based urinary metabolomics to find the changes of metabolic phenotypes in adolescent rats, which were exposed in the low concentration of R -metalaxyl and S -metalaxyl.…”