PMID- 11171526
OWN - NLM
STAT- MEDLINE
DCOM- 20010412
LR  - 20181113
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 109
IP  - 1
DP  - 2001 Jan
TI  - Evaluation of fish models of soluble epoxide hydrolase inhibition.
PG  - 61-6
AB  - Substituted ureas and carbamates are mechanistic inhibitors of the soluble 
      epoxide hydrolase (sEH). We screened a set of chemicals containing these 
      functionalities in larval fathead minnow (Pimphales promelas) and embryo/larval 
      golden medaka (Oryzias latipes) models to evaluate the utility of these systems 
      for investigating sEH inhibition in vivo. Both fathead minnow and medaka sEHs 
      were functionally similar to the tested mammalian orthologs (murine and human) 
      with respect to substrate hydrolysis and inhibitor susceptibility. Low lethality 
      was observed in either larval or embryonic fish exposed to diuron 
      [N-(3,4-dichlorophenyl), N'-dimethyl urea], desmethyl diuron 
      [N-(3,4-dichlorophenyl), N'-methyl urea], or siduron [N-(1-methylcyclohexyl), 
      N'-phenyl urea]. Dose-dependent inhibition of sEH was a sublethal effect of 
      substituted urea exposure with the potency of siduron < desmethyl diuron = 
      diuron, differing from the observed in vitro sEH inhibition potency of siduron > 
      desmethyl diuron > diuron. Further, siduron exposure synergized the toxicity of 
      trans-stilbene oxide in fathead minnows. Medaka embryos exposed to diuron, 
      desmethyl diuron, or siduron displayed dose-dependent delays in hatch, and 
      elevated concentrations of diuron and desmethyl diuron produced developmental 
      toxicity. The dose-dependent toxicity and in vivo sEH inhibition correlated, 
      suggesting a potential, albeit undefined, relationship between these factors. 
      Additionally, the observed inversion of in vitro to in vivo potency suggests that 
      these fish models may provide tools for investigating the in vivo stability of in 
      vitro inhibitors while screening for untoward effects.
FAU - Newman, J W
AU  - Newman JW
AD  - Department of Entomology, University of California, Davis, California 95616, USA.
FAU - Denton, D L
AU  - Denton DL
FAU - Morisseau, C
AU  - Morisseau C
FAU - Koger, C S
AU  - Koger CS
FAU - Wheelock, C E
AU  - Wheelock CE
FAU - Hinton, D E
AU  - Hinton DE
FAU - Hammock, B D
AU  - Hammock BD
LA  - eng
GR  - 732ES07059/ES/NIEHS NIH HHS/United States
GR  - CA 45131/CA/NCI NIH HHS/United States
GR  - P42ES04699/ES/NIEHS NIH HHS/United States
GR  - R01ES02710/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Herbicides)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Water Pollutants, Chemical)
RN  - 513S964LJO (siduron)
RN  - 9I3SDS92WY (Diuron)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Animals
MH  - Biological Assay/methods
MH  - Cyprinidae/physiology
MH  - Diuron/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Environmental Monitoring/methods
MH  - Epoxide Hydrolases/*antagonists & inhibitors/metabolism
MH  - Herbicides/*toxicity
MH  - Larva/drug effects/enzymology
MH  - Oryzias/physiology
MH  - Phenylurea Compounds/*toxicity
MH  - Water Pollutants, Chemical/*toxicity
PMC - PMC1242052
EDAT- 2001/02/15 11:00
MHDA- 2001/04/17 10:01
PMCR- 2001/01/01
CRDT- 2001/02/15 11:00
PHST- 2001/02/15 11:00 [pubmed]
PHST- 2001/04/17 10:01 [medline]
PHST- 2001/02/15 11:00 [entrez]
PHST- 2001/01/01 00:00 [pmc-release]
AID - sc271_5_1835 [pii]
AID - 10.1289/ehp.0110961 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2001 Jan;109(1):61-6. doi: 10.1289/ehp.0110961.