Characterization of triclosan-induced hepatotoxicity and triclocarban-triggered enterotoxicity in mice by multiple omics screening

Song, Yuanlin; Zhang, Cui; Lei, Hehua; Qin, Mengyu; Chen, Gui; Wu, Fang; Chen, Chuan; Cao, Zheng; Zhang, Ce; Wu, Mengjing; Chen, Xiaoyu; Zhang, Limin

doi:10.1016/j.scitotenv.2022.156570

Cited by 16 publications

(10 citation statements)

References 47 publications

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“…12 omics studies revealed that acute TCC exposure mainly induced significant intestine injury resulting in profound disruption of intestinal morphology and inflammation without significant liver injury, which suggested that the intestine could be the targeting toxic organ of TCC exposure. 13 We also found that TCC exposure dramatically aggravated DSS-induced mouse colitis via activation of inflammatory NF-κB signaling and disrupting the microbial community. 14 The detailed mechanism of TCC-triggered enterotoxicity warrants further investigation.…”

Section: Introductionmentioning

confidence: 62%

“…It was also reported that TCC exposure promoted adipogenesis of preadipocytes and hepatocytes and interrupted the maturation of mouse oocytes in vitro. More recently, our multiple omics studies revealed that acute TCC exposure mainly induced significant intestine injury resulting in profound disruption of intestinal morphology and inflammation without significant liver injury, which suggested that the intestine could be the targeting toxic organ of TCC exposure . We also found that TCC exposure dramatically aggravated DSS-induced mouse colitis via activation of inflammatory NF-κB signaling and disrupting the microbial community .…”

Section: Introductionmentioning

confidence: 71%

“…Based on allometric scaling calculations, TCC doses of 40 and 200 mg/kg body weight for mice used in this study are equivalent to 3.2 and 16.0 mg/kg human being that is ADI of TCC in adults, respectively . Our recent multiomics screening study revealed that targeting toxic organ of TCC exposure is the intestine, meaning that TCC mainly exhibits enterotoxicity . However, the mechanism underlying the enterotoxicity of TCC is still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…19 Our recent multiomics screening study revealed that targeting toxic organ of TCC exposure is the intestine, meaning that TCC mainly exhibits enterotoxicity. 13 However, the mechanism underlying the enterotoxicity of TCC is still unclear. In this study, doses of 40 and 200 mg/kg were regarded as chronic and acute exposure, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Long-Term Triclocarban Exposure Induced Enterotoxicity by Triggering Intestinal AhR-Mediated Inflammation and Disrupting Microbial Community in Mice

Song,

Lei,

Cao

et al. 2024

Chem. Res. Toxicol.

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Exposure to triclocarban (TCC), a commonly used antibacterial agent, has been shown to induce significant intestine injuries and colonic inflammation in mice. However, the detailed mechanisms by which TCC exposure triggered enterotoxicity remain largely unclear. Herein, intestinal toxicity effects of longterm and chronic TCC exposure were investigated using a combination of histopathological assessments, metagenomics, targeted metabolomics, and biological assays. Mechanically, TCC exposure caused induction of intestinal aryl hydrocarbon receptor (AhR) and its transcriptional target cytochrome P4501A1 (Cyp1a1) leading to dysfunction of the gut barrier and disruption of the gut microbial community. A large number of lipopolysaccharides (LPS) are released from the gut lumen into blood circulation owing to the markedly increased permeability and gut leakage. Consequently, toll-like receptor-4 (TLR4) and NF-κB signaling pathways were activated by high levels of LPS. Simultaneously, classic macrophage phenotypes were switched by TCC, shown with marked upregulation of macrophage M1 and downregulation of macrophage M2 that was accompanied by striking upregulation of proinflammatory factors such as Il-1β, Il-6, Il-17, and Tnf-α in the intestinal lamina propria. These findings provide new evidence for the TCC-induced enterotoxicity.

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Section: Introductionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Long-Term Triclocarban Exposure Induced Enterotoxicity by Triggering Intestinal AhR-Mediated Inflammation and Disrupting Microbial Community in Mice

Song,

Lei,

Cao

et al. 2024

Chem. Res. Toxicol.

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“…Transcriptomics analysis was performed on PHH and HepaRG cell culture samples collected after exposure to 2,7-naphthalediol (NPT), butylated hydroxytoluene (BHT) and triclosan (TCS) (Table S1) . Necrosis and steatosis have been observed in the liver of experimental animals following exposure to BHT (Scientific Committee on Consumer Safety, 2021a) and TCS (Song et al, 2022), respectively. In a review of animal toxicity data, NPT was found to alter three parameters associated with, and thus possibly indicative of, cholestasis, namely increased serum levels of gamma-glutamyl transferase and bilirubin, together with cellular necrosis (Gustafson et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

Systematic comparison of temporal transcriptional responses to hepatotoxicants in primary human hepatocytes and HepaRG cells using concentration-response modelling of gene co-expression networks

Kunnen

Arnesdotter

Willenbockel

et al. 2023

Preprint

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Next generation risk assessment of chemicals revolves around the use of mechanistic information without animal experimentation. In this regard, toxicogenomics has proven to be a useful tool to elucidate the underlying mechanisms of adverse effects of xenobiotics. In the present study, two widely used human in vitro hepatocyte culture systems, namely primary human hepatocytes (PHH) and human hepatoma HepaRG cells, were exposed to liver toxicants known to induce liver steatosis, cholestasis or necrosis. Benchmark concentration-response modelling was applied to transcriptomics gene co-expression networks (modules) in order to derive benchmark concentrations (BMCs) and to gain mechanistic insight into the hepatotoxic effects. BMCs derived by concentration-response modelling of gene co-expression modules recapitulated concentration-response modelling of individual genes. Although PHH and HepaRG cells showed overlap in deregulated genes and modules by the liver toxicants, PHH demonstrated a higher responsiveness, based on the lower BMCs of co-regulated gene modules. Such BMCs can be used as point of departure for assessing module-associated cellular (stress) pathways/processes. This approach could serve next generation risk assessment practice to identify early responsive modules at low BMCs. In turn, this can assist in delineating potential hazards of new test chemicals using in vitro systems when BMCs are paired with chemical exposure assessment and used in a subsequent risk assessment.

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Conceptualizing the Role of the Microbiome as a Mediator and Modifier in Environmental Health Studies: A Scoping Review of Studies of Triclosan and the Microbiome

Laue,

Gilmour,

Tirado

et al. 2024

Curr Envir Health Rpt

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Characterization of triclosan-induced hepatotoxicity and triclocarban-triggered enterotoxicity in mice by multiple omics screening

Cited by 16 publications

References 47 publications

Long-Term Triclocarban Exposure Induced Enterotoxicity by Triggering Intestinal AhR-Mediated Inflammation and Disrupting Microbial Community in Mice

Long-Term Triclocarban Exposure Induced Enterotoxicity by Triggering Intestinal AhR-Mediated Inflammation and Disrupting Microbial Community in Mice

Systematic comparison of temporal transcriptional responses to hepatotoxicants in primary human hepatocytes and HepaRG cells using concentration-response modelling of gene co-expression networks

Conceptualizing the Role of the Microbiome as a Mediator and Modifier in Environmental Health Studies: A Scoping Review of Studies of Triclosan and the Microbiome

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