@article {235,
	title = {Multi-omics reveals 2-bromo-4,6-dinitroaniline (BDNA)-induced hepatotoxicity and the role of the gut-liver axis in rats.},
	journal = {J Hazard Mater},
	volume = {457},
	year = {2023},
	month = {2023 Jun 03},
	pages = {131760},
	abstract = {<p>2-Bromo-4, 6-dinitroaniline (BDNA) is a widespread azo-dye-related hazardous pollutant. However, its reported adverse effects are limited to mutagenicity, genotoxicity, endocrine disruption, and reproductive toxicity. We systematically assessed the hepatotoxicity of BDNA exposure via pathological and biochemical examinations and explored the underlying mechanisms via integrative multi-omics analyses of the transcriptome, metabolome, and microbiome in rats. After 28 days of oral administration, compared with the control group, 100\&nbsp;mg/kg BDNA significantly triggered hepatotoxicity, upregulated toxicity indicators (e.g., HSI, ALT, and ARG1), and induced systemic inflammation (e.g., G-CSF, MIP-2, RANTES, and VEGF), dyslipidemia (e.g., TC and TG), and bile acid (BA) synthesis (e.g., CA, GCA, and GDCA). Transcriptomic and metabolomic analyses revealed broad perturbations in gene transcripts and metabolites involved in the representative pathways of liver inflammation (e.g., Hmox1, Spi1, L-methionine, valproic acid, and choline), steatosis (e.g., Nr0b2, Cyp1a1, Cyp1a2, Dusp1, Plin3, arachidonic acid, linoleic acid, and palmitic acid), and cholestasis (e.g., FXR/Nr1h4, Cdkn1a, Cyp7a1, and bilirubin). Microbiome analysis revealed reduced relative abundances of beneficial gut microbial taxa (e.g., Ruminococcaceae and Akkermansia muciniphila), which further contributed to the inflammatory response, lipid accumulation, and BA synthesis in the enterohepatic circulation. The observed effect concentrations here were comparable to the highly contaminated wastewaters, showcasing BDNA{\textquoteright}s hepatotoxic effects at environmentally relevant concentrations. These results shed light on the biomolecular mechanism and important role of the gut-liver axis underpinning BDNA-induced cholestatic liver disorders in vivo.</p>},
	issn = {1873-3336},
	doi = {10.1016/j.jhazmat.2023.131760},
	author = {Deng, Fuchang and Qin, Guangqiu and Chen, Yuanyuan and Zhang, Xu and Zhu, Mu and Hou, Min and Yao, Qiao and Gu, Wen and Wang, Chao and Yang, Hui and Jia, Xudong and Wu, Chongming and Peng, Hui and Du, Huamao and Tang, Song}
}
