title: A hepatic metabolomics-based diagnostic approach to assess lethal toxicity of dithiocarbamate fungicide polycarbamate in three marine fish species.
abstract: The present study was performed to evaluate the toxic effect of the dithiocarbamate fungicide polycarbamate (PC) on the hepatic metabolic profiles of three marine fish species, red sea bream (Pagrus major), spotted halibut (Verasper variegatus), and marbled flounder (Pleuronectes yokohamae). First, juvenile fish were exposed to graded concentrations of PC for 96h; the 96-h LC50values obtained were 22-29, 239-553, and 301-364µgL-1for red sea bream, spotted halibut, and marbled flounder, respectively, indicating that red sea bream possessed higher sensitivity to PC than the two benthic species. Second, the fish were exposed to lethal-equivalent concentration (H group) or sub-lethal (one-tenth of the H group concentrations; L group) for 24 and 96h and gas-chromatography based metabolomics approach was employed to explore the crucial biomarker metabolite associated with lethal toxicity. Of the 53 metabolites identified, only reduced glutathione (GSH) was consistently elevated in the H group for the three fish species at 96h. The calculated cut-off value of GSH (mM) based on receiver operating curve analysis between H group and the other treatment groups (control, solvent control, and L group) was obtained at 0.56mM, which allowed to distinguish between the groups with high confidence for the three fish species. These results are the first to demonstrate the potential of using GSH as a possible biomarker metabolite and its usefulness of threshold cut-off value for diagnosing life-threatening health conditions of fish.
authors.affiliation: National Research Institute of Fisheries and Environment of Inland Sea, Fisheries Research and Education Agency, 2-17-5 Maruishi, Hatsukaichi, Hiroshima 739-0452, Japan. Electronic address: hntks@affrc.go.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hano
authors.affiliation: National Research Institute of Fisheries and Environment of Inland Sea, Fisheries Research and Education Agency, 2-17-5 Maruishi, Hatsukaichi, Hiroshima 739-0452, Japan. Electronic address: nobuyuki@affrc.go.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ohkubo
authors.affiliation: National Research Institute of Fisheries and Environment of Inland Sea, Fisheries Research and Education Agency, 2-17-5 Maruishi, Hatsukaichi, Hiroshima 739-0452, Japan. Electronic address: kmochida@affrc.go.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Mochida
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D054750:Ecotoxicology; D005399:Fishes / Q000502:physiology*; D005659:Fungicides, Industrial / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D055432:Metabolomics; D012016:Reference Values; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D005659:Fungicides, Industrial; D014874:Water Pollutants, Chemical; D005978:Glutathione
keywords: Diagnostic biomarker; Hepatic metabolomics; Lethal toxicity; Polycarbamate; Reduced glutathione