In vitro evaluation of the hepatic lipid accumulation of bisphenol analogs: A high-content screening assay

Liu, Qian; Shao, Wentao; Weng, Zhenkun; Zhang, Xin; Ding, Guofu; Xu, Cheng; Xu, Jin; Jiang, Zhaoyan; Gu, Aihua

doi:10.1016/j.tiv.2020.104959

Cited by 24 publications

(22 citation statements)

References 66 publications

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“…Liu et al observed a significant increase in the TAG level in human hepatoma HepG2 cells after in vitro exposure to bisphenol AP or tetramethylbisphenol A. 54 When exposing to 1 mg/kg BDE-47 (one of polybrominated diphenyl ethers) or low-dose (50 and 500 μg/kg) bisphenol A, accumulation of TAG in the mouse liver was significantly determined. 55,56 In the current study, the increase in the TAG level observed at 24 h and 7 d suggested the accumulation of lipotoxic fatty acids, and the actual effect on the hepatic lipid metabolism induced by the administration of environmentally relevant concentrations of both TBBPA and TBBPA-BDBPE.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…studies aiming at bisphenol analogues and other BFRs have reported that changes in the expression of genes involved in lipogenesis, lipid trafficking, lipid β-oxidation, and nuclear receptors mechanistically resulted in the alteration of lipid metabolism (including TAG accumulation) in the liver. [54][55][56]58 In our study, by exposure to environmentally relevant dose of TBBPA or TBBPA-BDBPE, we determined the upregulated expression of Lpin1, encoding a necessary protein in the synthesis of TAG. 45 Alterations in Macrophage Populations in the Liver.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Toxicity of Tetrabromobisphenol A and Its Derivative in the Mouse Liver Following Oral Exposure at Environmentally Relevant Levels

Yao

Wang

Shi

et al. 2021

Environ. Sci. Technol.

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As typical brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA) and its derivative TBBPA-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) are ubiquitous in various environmental compartments. However, the potential health risk posed by these compounds, especially at environmentally relevant levels, remains unclear. In this study, using adult male mice, we investigated the toxicity of orally administered TBBPA and TBBPA-BDBPE at an environmentally relevant dose (57 nmol/kg body weight). After a single exposure and daily exposure, we assessed lipid metabolism homeostasis, the transcriptome, and immune cell components in the liver. We found that the single exposure to TBBPA or TBBPA-BDBPE alone increased the number of hepatic macrophages, induced alterations in the levels of lipids, including triacylglycerol and free fatty acids, and caused transcriptome perturbation. The results from the daily administration groups showed that TBBPA and TBBPA-BDBPE both significantly increased the triacylglycerol content; however, the elevation of hepatic macrophages was observed only in the TBBPA-BDBPE treatment group. This study confirmed that environmentally relevant levels of TBBPA and TBBPA-BDBPE are toxic to the liver. Our findings revealed that dysfunction of the liver is a health concern, following exposure to BFRs, even at very low concentrations. The chronic effects induced by TBBPA and its derivatives should be further investigated.

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Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

Toxicity of Tetrabromobisphenol A and Its Derivative in the Mouse Liver Following Oral Exposure at Environmentally Relevant Levels

Yao

Wang

Shi

et al. 2021

Environ. Sci. Technol.

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“…Another replacement compound, BPS, upregulated the hepatic expression of CYP7B1, which is involved in the alternative pathway of bile acid synthesis in chickens (Crump et al 2016). In previous studies, BPAF upregulated the expression of SCD and other lipid metabolism genes in HepG2 and 3T3-L1cells (Liu et al 2020;Skledar et al 2019). POLB is involved in base excision repair by incorporating the correct base at the site of single stranded breaks (Martin et al 2010).…”

Section: Resultsmentioning

confidence: 92%

“…The rank order of the chemicals evaluated in the present study based on LC50 in LMH spheroids was BPAF ~ DD-70 > TGSH ~ B PA ~ BPSIP ~ BPF. BPAF and BPF were one of the most and least cytotoxic, respectively, among several BPA replacement compounds screened in various cell lines (Liu et al 2020;Russo et al 2018;Goldinger et al 2015). No other cell viability data exist for TSGH or DD-70.…”

Section: Resultsmentioning

confidence: 99%

Toxicity screening of bisphenol A replacement compounds: cytotoxicity and mRNA expression in LMH 3D spheroids

Sharin

Crump

O’Brien

2022

Environ Sci Pollut Res

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Previously, we showed that the chicken LMH cell line cultured as 3D spheroids may be a suitable animal free alternative to primary chicken embryonic hepatocytes (CEH) for avian in vitro chemical screening. In this study, cytotoxicity and mRNA expression were determined in LMH 3D spheroids following exposure to bisphenol A (BPA), five BPA replacement compounds (BPF, TGSH, DD-70, BPAF, BPSIP), and 17β estradiol (E2). Results were compared to an earlier study that evaluated the same endpoints for these chemicals in CEH. BPA and the replacement compounds had LC50 values ranging from 16.6 to 81.8 μM; DD-70 and BPAF were the most cytotoxic replacements (LC50 = 17.23 ± 4.51 and 16.6 ± 4.78 μM). TGSH and DD-70 modulated the greatest number of genes, although fewer than observed in CEH. Based on the expression of apovitellenin and vitellogenin, BPAF was the most estrogenic compound followed by BPF, BPSIP, and BPA. More estrogen-responsive genes were modulated in LMH spheroids compared to CEH. Concentration-dependent gene expression revealed that DD-70 and BPAF altered genes related to lipid and bile acid regulation. Overall, cytotoxicity and clustering of replacements based on gene expression profiles were similar between LMH spheroids and CEH. In addition to generating novel gene expression data for five BPA replacement compounds in an in vitro avian model, this research demonstrates that LMH spheroids may represent a useful animal free alternative for avian toxicity testing.

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“…BPA could also have direct effects on hepatocytes. Indeed, several in vitro studies showed that BPA induced lipid accretion in the human hepatic cell lines HepG2, HepaRG and HHL-5 [119][120][121][122][123][124][125][126]. This effect was observed for BPA concentrations in the nanomolar range in four independent studies [119,120,123,125], with a non-monotonic profile observed in three of them [119,123,125].…”

Section: Bisphenol Amentioning

confidence: 94%

Xenobiotic-Induced Aggravation of Metabolic-Associated Fatty Liver Disease

Massart¹,

Begriche²,

Corlu³

et al. 2022

IJMS

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Metabolic-associated fatty liver disease (MAFLD), which is often linked to obesity, encompasses a large spectrum of hepatic lesions, including simple fatty liver, steatohepatitis, cirrhosis and hepatocellular carcinoma. Besides nutritional and genetic factors, different xenobiotics such as pharmaceuticals and environmental toxicants are suspected to aggravate MAFLD in obese individuals. More specifically, pre-existing fatty liver or steatohepatitis may worsen, or fatty liver may progress faster to steatohepatitis in treated patients, or exposed individuals. The mechanisms whereby xenobiotics can aggravate MAFLD are still poorly understood and are currently under deep investigations. Nevertheless, previous studies pointed to the role of different metabolic pathways and cellular events such as activation of de novo lipogenesis and mitochondrial dysfunction, mostly associated with reactive oxygen species overproduction. This review presents the available data gathered with some prototypic compounds with a focus on corticosteroids and rosiglitazone for pharmaceuticals as well as bisphenol A and perfluorooctanoic acid for endocrine disruptors. Although not typically considered as a xenobiotic, ethanol is also discussed because its abuse has dire consequences on obese liver.

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In vitro evaluation of the hepatic lipid accumulation of bisphenol analogs: A high-content screening assay

Cited by 24 publications

References 66 publications

Toxicity of Tetrabromobisphenol A and Its Derivative in the Mouse Liver Following Oral Exposure at Environmentally Relevant Levels

Toxicity of Tetrabromobisphenol A and Its Derivative in the Mouse Liver Following Oral Exposure at Environmentally Relevant Levels

Toxicity screening of bisphenol A replacement compounds: cytotoxicity and mRNA expression in LMH 3D spheroids

Xenobiotic-Induced Aggravation of Metabolic-Associated Fatty Liver Disease

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