title: Acute Exposure to Tris(1,3-dichloro-2-propyl) Phosphate (TDCIPP) Causes Hepatic Inflammation and Leads to Hepatotoxicity in Zebrafish.
abstract: Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been frequently detected in environmental media and has adverse health effect on wildlife and humans. It has been implicated to have hepatotoxicity, but its molecular mechanisms remain unclear. In the present study, adult male zebrafish were exposed to TDCIPP and global hepatic gene expression was examined by RNA-Seq and RT-qPCR in order to understand the molecular mechanisms of TDCIPP-induced hepatotoxicity. Our results indicated that TDCIPP exposure significantly up-regulated the expression of genes involved in endoplasmic reticulum stress and Toll-like receptor (TLR) pathway, implying an inflammatory response, which was supported by up-regulation of inflammation-related biomaker genes. Hepatic inflammation was further confirmed by histological observation of increase of infiltrated neutrophils and direct observation of liver recruitment of neutrophils labeled with Ds-Red fluorescent protein of Tg(lysC:DsRed) zebrafish upon TDCIPP exposure. To further characterize the hepatotoxicity of TDCIPP, the expression of hepatotoxicity biomarker genes, liver histopathology and morphology were examined. The exposure to TDCIPP significantly up-regulated the expression of several biomarker genes for hepatotoxicity (gck, gsr and nqo1) and caused hepatic vacuolization and apoptosis as well as increase of the liver size. Collectively, our results suggest that exposure to TDCIPP induces hepatic inflammation and leads to hepatotoxicity in zebrafish.
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.|Collaborative Innovation Center for Efficient and Health Production of Fisheries in Hunan Province.|Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada.|State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Guanyong
authors.initials: G
authors.lastname: Su
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.|Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada.|Department of Zoology and Centre for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, United States.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: Department of Chemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Letcher
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Ira
authors.initials: I
authors.lastname: Agrawal
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Yu
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Gong
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004625:Embryo, Nonmammalian; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005411:Flame Retardants / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D000081410:Germinal Center Kinases; D007249:Inflammation; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009943:Organophosphorus Compounds / Q000633:toxicity*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D005411:Flame Retardants; D000081410:Germinal Center Kinases; D008164:Luminescent Proteins; D009943:Organophosphorus Compounds; D051193:Toll-Like Receptors; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; C413663:fluorescent protein 583; C016805:tris(1,3-dichloro-2-propyl)phosphate; D016660:NAD(P)H Dehydrogenase (Quinone); D017346:Protein Serine-Threonine Kinases