Aryl-, halogenated- and alkyl- organophosphate esters induced oxidative stress, endoplasmic reticulum stress and NLRP3 inflammasome activation in HepG2 cells

Organophosphate esters (OPEs) are a group of extensively used man-made chemicals with diverse substituents that are ubiquitously detected in human-related samples including serum, breastmilk, food and house dust. The understanding of their toxicological effects and potential mechanisms on hepatocyte...

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Veröffentlicht in:Environmental pollution (1987) 2023-01, Vol.316, p.120559, Article 120559
Hauptverfasser: Zhou, Yuanyuan, Liao, Hanyu, Yin, Shanshan, Wang, Pengqiao, Ye, Xiaoqing, Zhang, Jianyun
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Sprache:eng
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Zusammenfassung:Organophosphate esters (OPEs) are a group of extensively used man-made chemicals with diverse substituents that are ubiquitously detected in human-related samples including serum, breastmilk, food and house dust. The understanding of their toxicological effects and potential mechanisms on hepatocytes is still limited. In this study, nine most frequently detected OPEs were selected and divided into three subgroups (aryl-, halogenated- and alkyl-OPEs) based on their substituents. The cytotoxicity, apoptosis, oxidative stress, endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation induced by OPEs were evaluated in human hepatocellular carcinomas HepG2 cells. All OPEs induced apoptosis likely through a caspase-dependent apoptotic pathway. The activities of anti-oxidative enzyme SOD and CAT exhibited sensitive responses after OPEs treatment for 6 h. The OPEs induced ROS overproduction, DNA damage, endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation varied among aryl-, halogenated- and alkyl-OPEs. Halogenated- and alkyl- OPEs induced overproduction of ROS and DNA damage, and elevated ER stress and NLRP3 inflammasome activation are observed aryl-OPEs induced cytotoxicity. [Display omitted] •Cytotoxicity of 3 aryl-, 2 halogenated- and 4 alkyl-OPEs was observed in HepG2 Cells.•The cytotoxic effects of OPEs were correlated with their LogKow values.•Halogenated- and alkyl- OPEs induced overproduction of ROS, but not aryl-OPEs.•Aryl-OPEs elevated ER stress and induced NLRP3 inflammasome activation.
ISSN:0269-7491
1873-6424
DOI:10.1016/j.envpol.2022.120559