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Soluble Epoxide Hydrolase Activity Determines the Severity of Ischemia-Reperfusion Injury in Kidney

Cited 32 time in Web of Science Cited 43 time in Scopus
Authors

Lee, Jung Pyo; Yang, Seung Hee; Lee, Hee-Yoon; Kim, Bora; Cho, Joo-Youn; Paik, Jin Ho; Oh, Yun Jung; Kim, Dong Ki; Lim, Chun Soo; Kim, Yon Su

Issue Date
2012-05
Publisher
Public Library of Science
Citation
PLoS ONE, Vol.7 No.5, p. e37075
Abstract
Soluble epoxide hydrolase (sEH) in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs), which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI) in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA). The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME) and its metabolite dihydroxyoctadec-12-enoic acid (DHOME). Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury.
ISSN
1932-6203
URI
https://hdl.handle.net/10371/192090
DOI
https://doi.org/10.1371/journal.pone.0037075
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Paik, Jin Ho백진호
(기금)부교수
  • College of Medicine
  • Department of Medicine
Research Area Head and Neck Pathology, Hematopathology, Renal Pathology, 두경부병리학, 신장병리학, 혈액병리학

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