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Journal of Hazardous Materials

Journal of Hazardous Materials

IF: 12.2
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AHR-mediated oxidative stress contributes to the cardiac developmental toxicity of trichloroethylene in zebrafish embryos

Published:5 March 2020 DOI: 10.1016/j.jhazmat.2019.121521 PMID: 31699484
Hongmei Jin , Cheng Ji , Fei Ren , Stanley Aniagu , Jian Tong , Yan Jiang , Tao Chen

Abstract

Trichloroethylene (TCE), a widely used chlorinated solvent, is a common environmental pollutant. Current evidence shows that TCE could induce heart defects during embryonic development, but the underlining mechanism(s) remain unclear. Since activation of the aryl hydrocarbon receptor (AHR) could induce oxidative stress, we hypothesized that AHR-mediated oxidative stress may play a role in the cardiac developmental toxicity of TCE. In this study, we found that the reactive oxygen species (ROS) scavenger, N-Acetyl-L-cysteine (NAC), and AHR inhibitors, CH223191 (CH) and StemRegenin 1, significantly counteracted the TCE-induced heart malformations in zebrafish embryos. Moreover, both CH and NAC suppressed TCE-induced ROS and 8-OHdG (8-hydroxy-2′ -deoxyguanosine). TCE did not affect ahr2 and cyp1a expression, but increased cyp1b1 expression, which was restored by CH supplementation. CH also attenuated the TCE-induced mRNA expression changes of Nrf2 signalling genes (nrf2b, gstp2, sod2, ho1, nqo1) and cardiac differentiation genes (gata4, hand2, c-fos, sox9b). In addition, the TCE enhanced SOD activity was attenuated by CH. Morpholino knockdown confirmed that AHR mediated the TCE-induced ROS and 8-OHdG generation in the heart of zebrafish embryos. In conclusion, our results suggest that AHR mediates TCE-induced oxidative stress, leading to DNA damage and heart malformations in zebrafish embryos.

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Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
SteMRegenin 1 1227633-49-9 C24H23N5OS 142 suppliers $20.00-$2395.30
SteMRegenin 1 1227633-49-9 C24H23N5OS 142 suppliers $20.00-$2395.30
SteMRegenin 1 1227633-49-9 C24H23N5OS 142 suppliers $20.00-$2395.30
SteMRegenin 1 1227633-49-9 C24H23N5OS 142 suppliers $20.00-$2395.30

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