PMID- 18187559
OWN - NLM
STAT- MEDLINE
DCOM- 20080410
LR  - 20161124
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 102
IP  - 2
DP  - 2008 Apr
TI  - Protective response of the Ah receptor to ANIT-induced biliary epithelial cell 
      toxicity in see-through medaka.
PG  - 262-77
LID - 10.1093/toxsci/kfm308 [doi]
AB  - The adaptive role of the aryl hydrocarbon receptor (Ah receptor or AHR) in 
      protecting against disease-related conditions remains unclear in nonmammalian 
      models, particularly teleosts. Therefore, this study focused on the potential 
      role of AHR in response to biliary epithelial cell toxicity and hepatobiliary 
      alteration in medaka. See-through medaka (STII strain) were exposed for 96 h 
      using the biliary toxicant alpha-naphthylisothiocyanate (ANIT) as a reagent, and 
      fish were evaluated daily using histological and ultrastructural analysis, and by 
      imaging directly through the body wall of living fish. Brightfield and 
      transmission electron microscopy showed that a single ANIT dose (40 mg/kg) 
      specifically induced swelling and apoptosis of bile preductular epithelial cells 
      (BPDECs) as early as 6 h after initial exposure. Following ANIT-induced BPDEC 
      toxicity, in vivo imaging of STII medaka showed significant gallbladder 
      discoloration from 48-72 h. Collectively, these pathologic data suggested that 
      ANIT exposure resulted in acute hepatobiliary changes, lasting < 96 h following 
      initial exposure. We then tested the potential role of AHR in response to 
      ANIT-induced hepatobiliary alteration. Overall, we demonstrated that (1) 
      transient AHR activation and cytochrome P450 1A (CYP1A) induction in livers 
      occurred during ANIT-induced hepatobiliary impairment, (2) pretreatment with an 
      AHR agonist partially protected against acute hepatobiliary alteration, and (3) 
      using a luciferase-based reporter assay, the bile pigment bilirubin weakly 
      activated mouse AHR and binding to medaka-specific CYP1A promoter, resulting in 
      AHR element-driven transcription. Given that bile acids and pigments are present 
      in mammalian and fish liver, these studies collectively suggest that bile-induced 
      AHR activation may be conserved between teleosts and rodents.
FAU - Volz, David C
AU  - Volz DC
AD  - Integrated Toxicology Program and Nicholas School of the Environment and Earth 
      Sciences, Duke University, Durham, North Carolina 27708.
FAU - Kullman, Seth W
AU  - Kullman SW
FAU - Howarth, Deanna L
AU  - Howarth DL
FAU - Hardman, Ron C
AU  - Hardman RC
FAU - Hinton, David E
AU  - Hinton DE
LA  - eng
GR  - 1R01 RR018583-03/RR/NCRR NIH HHS/United States
GR  - 5R21CA106084-02/CA/NCI NIH HHS/United States
GR  - T32 ES07031/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080110
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 551-06-4 (1-Naphthylisothiocyanate)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - 1-Naphthylisothiocyanate/*toxicity
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Bile Ducts, Intrahepatic/*drug effects/metabolism/pathology
MH  - Bilirubin/pharmacology
MH  - Cell Line, Tumor
MH  - Cholestasis, Intrahepatic/metabolism/*prevention & control
MH  - Cloning, Molecular
MH  - Cytochrome P-450 CYP1A1/biosynthesis/genetics
MH  - Disease Models, Animal
MH  - Drug Antagonism
MH  - Enzyme Induction
MH  - Epithelial Cells/drug effects/metabolism/ultrastructure
MH  - Gallbladder/drug effects/pathology
MH  - Gene Expression/drug effects
MH  - Injections, Intraperitoneal
MH  - Liver/drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Oryzias/*physiology
MH  - Pigmentation/genetics
MH  - Polychlorinated Dibenzodioxins/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Aryl Hydrocarbon/*agonists/drug effects/*metabolism
EDAT- 2008/01/12 09:00
MHDA- 2008/04/11 09:00
CRDT- 2008/01/12 09:00
PHST- 2008/01/12 09:00 [pubmed]
PHST- 2008/04/11 09:00 [medline]
PHST- 2008/01/12 09:00 [entrez]
AID - kfm308 [pii]
AID - 10.1093/toxsci/kfm308 [doi]
PST - ppublish
SO  - Toxicol Sci. 2008 Apr;102(2):262-77. doi: 10.1093/toxsci/kfm308. Epub 2008 Jan 
      10.