title: Non invasive high resolution in vivo imaging of alpha-naphthylisothiocyanate (ANIT) induced hepatobiliary toxicity in STII medaka.
abstract: A novel transparent stock of medaka (Oryzias latipes; STII), homozygous recessive for all four pigments (iridophores, xanthophores, leucophores, melanophores), permits transcutaneous, high resolution (<1 microm) imaging of internal organs and tissues in living individuals. We applied this model to in vivo investigation of alpha -naphthylisothiocyanate (ANIT) induced hepatobiliary toxicity. Distinct phenotypic responses to ANIT involving all aspects of intrahepatic biliary passageways (IHBPs), particularly bile preductular epithelial cells (BPDECs), associated with transitional passageways between canaliculi and bile ductules, were observed. Alterations included: attenuation/dilation of bile canaliculi, bile preductular lesions, hydropic vacuolation of hepatocytes and BPDECs, mild BPDEC hypertrophy, and biliary epithelial cell (BEC) hyperplasia. Ex vivo histological, immunohistochemical, and ultrastructural studies were employed to aid in interpretation of, and verify, in vivo findings. 3D reconstructions from in vivo investigations provided quantitative morphometric and volumetric evaluation of ANIT exposed and untreated livers. The findings presented show for the first time in vivo evaluation of toxicity in the STII medaka hepatobiliary system, and, in conjunction with prior in vivo work characterizing normalcy, advance our comparative understanding of this lower vertebrate hepatobiliary system and its response to toxic insult.
authors.affiliation: Duke University, Nicholas School of the Environment and Earth Sciences, Durham, NC 27708, USA. ron.hardman@duke.edu
authors.forename: Ron
authors.initials: R
authors.lastname: Hardman
authors.forename: Seth
authors.initials: S
authors.lastname: Kullman
authors.forename: Bonny
authors.initials: B
authors.lastname: Yuen
authors.forename: David E
authors.initials: DE
authors.lastname: Hinton
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000633:toxicity*; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D017209:Apoptosis; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D001808:Blood Vessels / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005456:Fluorescent Dyes / Q000032:analysis; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional / Q000662:veterinary; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D018613:Microscopy, Confocal / Q000662:veterinary; D023421:Models, Animal; D009990:Oryzias / Q000235:genetics / Q000502:physiology*; D010641:Phenotype
chemical_list: D000906:Antibodies; D005456:Fluorescent Dyes; D015058:1-Naphthylisothiocyanate