PMID- 20694143
OWN - NLM
STAT- MEDLINE
DCOM- 20101104
LR  - 20240315
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 8
DP  - 2010 Aug 4
TI  - Inhibition of the soluble epoxide hydrolase promotes albuminuria in mice with 
      progressive renal disease.
PG  - e11979
LID - 10.1371/journal.pone.0011979 [doi]
LID - e11979
AB  - Epoxyeicotrienoic acids (EETs) are cytochrome P450-dependent anti-hypertensive 
      and anti-inflammatory derivatives of arachidonic acid, which are highly abundant 
      in the kidney and considered reno-protective. EETs are degraded by the enzyme 
      soluble epoxide hydrolase (sEH) and sEH inhibitors are considered treatment for 
      chronic renal failure (CRF). We determined whether sEH inhibition attenuates the 
      progression of CRF in the 5/6-nephrectomy model (5/6-Nx) in mice. 5/6-Nx mice 
      were treated with a placebo, an ACE-inhibitor (Ramipril, 40 mg/kg), the 
      sEH-inhibitor cAUCB or the CYP-inhibitor fenbendazole for 8 weeks. 5/6-Nx induced 
      hypertension, albuminuria, glomerulosclerosis and tubulo-interstitial damage and 
      these effects were attenuated by Ramipril. In contrast, cAUCB failed to lower the 
      blood pressure and albuminuria was more severe as compared to placebo. Plasma 
      EET-levels were doubled in 5/6 Nx-mice as compared to sham mice receiving 
      placebo. Renal sEH expression was attenuated in 5/6-Nx mice but cAUCB in these 
      animals still further increased the EET-level. cAUCB also increased 5-HETE and 
      15-HETE, which derive from peroxidation or lipoxygenases. Similar to cAUCB, 
      CYP450 inhibition increased HETEs and promoted albuminuria. Thus, sEH-inhibition 
      failed to elicit protective effects in the 5/6-Nx model and showed a tendency to 
      aggravate the disease. These effects might be consequence of a shift of 
      arachidonic acid metabolism into the lipoxygenase pathway.
FAU - Jung, Oliver
AU  - Jung O
AD  - Institut fur Kardiovaskulare Physiologie, Fachbereich Medizin der 
      Goethe-Universitat, Frankfurt am Main, Germany.
FAU - Jansen, Felix
AU  - Jansen F
FAU - Mieth, Anja
AU  - Mieth A
FAU - Barbosa-Sicard, Eduardo
AU  - Barbosa-Sicard E
FAU - Pliquett, Rainer U
AU  - Pliquett RU
FAU - Babelova, Andrea
AU  - Babelova A
FAU - Morisseau, Christophe
AU  - Morisseau C
FAU - Hwang, Sung H
AU  - Hwang SH
FAU - Tsai, Cindy
AU  - Tsai C
FAU - Hammock, Bruce D
AU  - Hammock BD
FAU - Schaefer, Liliana
AU  - Schaefer L
FAU - Geisslinger, Gerd
AU  - Geisslinger G
FAU - Amann, Kerstin
AU  - Amann K
FAU - Brandes, Ralf P
AU  - Brandes RP
LA  - eng
GR  - R01 HL059699/HL/NHLBI NIH HHS/United States
GR  - HL59699/HL/NHLBI NIH HHS/United States
GR  - R01 ER02710/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100804
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Epoxy Compounds)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.13.11.12 (Lipoxygenase)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Albuminuria/*chemically induced/complications/pathology
MH  - Animals
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - *Disease Progression
MH  - Enzyme Inhibitors/*pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors/*chemistry
MH  - Epoxy Compounds/blood
MH  - Kidney Failure, Chronic/blood/*complications/*pathology/surgery
MH  - Lipoxygenase/blood/metabolism
MH  - Mice
MH  - Nephrectomy
MH  - Proteinuria/complications/pathology
MH  - Solubility
PMC - PMC2915917
COIS- Competing Interests: BDH is a George and Judy Marcus Senior Fellow of the 
      American Asthma Foundation.
EDAT- 2010/08/10 06:00
MHDA- 2010/11/05 06:00
PMCR- 2010/08/04
CRDT- 2010/08/10 06:00
PHST- 2010/05/02 00:00 [received]
PHST- 2010/07/10 00:00 [accepted]
PHST- 2010/08/10 06:00 [entrez]
PHST- 2010/08/10 06:00 [pubmed]
PHST- 2010/11/05 06:00 [medline]
PHST- 2010/08/04 00:00 [pmc-release]
AID - 10-PONE-RA-18497R1 [pii]
AID - 10.1371/journal.pone.0011979 [doi]
PST - epublish
SO  - PLoS One. 2010 Aug 4;5(8):e11979. doi: 10.1371/journal.pone.0011979.