PMID- 27211013
OWN - NLM
STAT- MEDLINE
DCOM- 20170213
LR  - 20170213
IS  - 1532-0456 (Print)
IS  - 1532-0456 (Linking)
VI  - 188
DP  - 2016 Oct
TI  - Embryonic cardiotoxicity of weak aryl hydrocarbon receptor agonists and CYP1A 
      inhibitor fluoranthene in the Atlantic killifish (Fundulus heteroclitus).
PG  - 45-51
LID - S1532-0456(16)30062-X [pii]
LID - 10.1016/j.cbpc.2016.05.005 [doi]
AB  - High affinity aryl hydrocarbon receptor (AHR) ligands, such as certain 
      polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), cause 
      severe cardiac teratogenesis in fish embryos. Moderately strong AHR agonists, for 
      example benzo[a]pyrene and beta-naphthoflavone, are capable of causing similar 
      cardiotoxic effects, particularly when coupled with cytochrome P450 1A (CYP1A) 
      inhibitors (e.g., fluoranthene (FL). Additionally, some weaker AHR agonists 
      (carbaryl, 2-methylindole, 3-methylindole, and phenanthrene) are known to also 
      cause cardiotoxicity in zebrafish (Danio rerio) embryos when coupled with FL; 
      however, the cardiotoxic effects were not mediated specifically by AHR 
      stimulation. This study was performed to determine if binary exposure to weak AHR 
      agonists and FL were also capable of causing cardiotoxicity in Atlantic killifish 
      Fundulus heteroclitus embryos. Binary exposures were performed in both naive and 
      PAH-adapted killifish embryos to examine resistance to weak agonists and FL 
      binary exposures. Weak agonists used in this study included the following: 
      carbaryl, phenanthrene, 2-methylindole, 3-methylindole, indigo, and indirubin. 
      Carbaryl, indigo, and indirubin induced the highest CYP1 activity levels in naive 
      killifish embryos, but no significant CYP1 induction was observed in the 
      PAH-adapted killifish. Embryos were coexposed to subteratogenic levels of each 
      agonist and 500mug/L FL to assess if binary administration could cause 
      cardiotoxicity. Indigo and indirubin coupled with FL caused cardiac teratogenesis 
      in naive killifish, but coexposures did not produce cardiac chamber abnormalities 
      in the PAH-adapted population. Knockdown of AHR2 in naive killifish embryos did 
      not prevent cardiac teratogenesis. The data suggest a unique mechanism of 
      cardiotoxicity that is not driven by AHR2 activation.
CI  - Copyright (c) 2016. Published by Elsevier Inc.
FAU - Brown, D R
AU  - Brown DR
AD  - Nicholas School of the Environment, Duke University, Durham, NC 27514, USA. 
      Electronic address: daniel.r.browndu@gmail.com.
FAU - Clark, B W
AU  - Clark BW
AD  - Nicholas School of the Environment, Duke University, Durham, NC 27514, USA. 
      Electronic address: bwclark8@gmail.com.
FAU - Garner, L V T
AU  - Garner LV
AD  - Nicholas School of the Environment, Duke University, Durham, NC 27514, USA. 
      Electronic address: lvtgarner@gmail.com.
FAU - Di Giulio, R T
AU  - Di Giulio RT
AD  - Nicholas School of the Environment, Duke University, Durham, NC 27514, USA. 
      Electronic address: richd@duke.edu.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20160520
PL  - United States
TA  - Comp Biochem Physiol C Toxicol Pharmacol
JT  - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP
JID - 100959500
RN  - 0 (Cytochrome P-450 Enzyme Inhibitors)
RN  - 0 (Fish Proteins)
RN  - 0 (Fluorenes)
RN  - 0 (Ligands)
RN  - 0 (Polycyclic Aromatic Hydrocarbons)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Water Pollutants, Chemical)
RN  - 360UOL779Z (fluoranthene)
RN  - EC 1.14.14.1 (Cytochrome P450 Family 1)
SB  - IM
MH  - Animals
MH  - Cardiotoxicity
MH  - Cytochrome P-450 Enzyme Inhibitors/*toxicity
MH  - Cytochrome P450 Family 1/*antagonists & inhibitors/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Embryo, Nonmammalian/drug effects/enzymology
MH  - Fish Proteins/*agonists/*antagonists & inhibitors/metabolism
MH  - Fluorenes/*toxicity
MH  - Fundulidae/embryology/genetics/*metabolism
MH  - Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Heart/*drug effects
MH  - Ligands
MH  - Myocardium/*enzymology
MH  - Polycyclic Aromatic Hydrocarbons/*toxicity
MH  - Receptors, Aryl Hydrocarbon/*agonists/genetics/metabolism
MH  - Risk Assessment
MH  - Water Pollutants, Chemical/*toxicity
OTO - NOTNLM
OT  - Aryl hydrocarbon receptor agonists
OT  - Cardiotoxicity
OT  - Cytochrome P450
OT  - Development
OT  - Fundulus heteroclitus
OT  - Morpholino
EDAT- 2016/05/24 06:00
MHDA- 2017/02/14 06:00
CRDT- 2016/05/24 06:00
PHST- 2015/10/11 00:00 [received]
PHST- 2016/05/09 00:00 [revised]
PHST- 2016/05/15 00:00 [accepted]
PHST- 2016/05/24 06:00 [entrez]
PHST- 2016/05/24 06:00 [pubmed]
PHST- 2017/02/14 06:00 [medline]
AID - S1532-0456(16)30062-X [pii]
AID - 10.1016/j.cbpc.2016.05.005 [doi]
PST - ppublish
SO  - Comp Biochem Physiol C Toxicol Pharmacol. 2016 Oct;188:45-51. doi: 
      10.1016/j.cbpc.2016.05.005. Epub 2016 May 20.