Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation

Hutchens, Michael P.; Nakano, Takuma; Dunlap, Jennifer; Traystman, Richard J.; Hurn, Patricia D.; Alkayed, Nabil J.

doi:10.1016/j.resuscitation.2007.06.031

Cited by 59 publications

(51 citation statements)

References 25 publications

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“…However, in cardiac arrest (CA) and the resuscitation mouse model, the survival rate of sEH knockout mice model was significantly lower than wild-type, and reduced sEH levels or function reduce survival from cardiac arrest. This result is contrary to the previous hypothesis that sEH gene deletion improves survival and protect against ischemia/reperfusion injury [36]. To find subcellular location and genetic polymorphisms of sEH, sEH cDNA was cloned into vectors and transfected into different cell lines.…”

Section: Introductioncontrasting

confidence: 65%

“…In the acute systemic inflammation model, the sEH-null mice show a survival advantage over normal control [35]. In sEH-null mice, plasma levels of epoxy fatty acids were increased, fatty acid diols levels were decreased, and renal formation of epoxyeicosatrienoic and dihydroxyeicosatrienoic acids was markedly lower for versus wild-type mice [36,37]. However, in cardiac arrest (CA) and the resuscitation mouse model, the survival rate of sEH knockout mice model was significantly lower than wild-type, and reduced sEH levels or function reduce survival from cardiac arrest.…”

Section: Introductionmentioning

confidence: 99%

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Soluble Epoxide Hydrolase: Potential Target for Inflammation and Inflammation-Driven Cancer

Lou¹,

Zhang²,

Wang³

et al. 2017

J Carcinog Mutagen

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Arachidonic acid can be catalyzed by three different kind of metabolizing enzyme: cyclooxygenase (COX), lipoxygenase (LOX) and/or cytochrome P450 (CYP), and they produce prostaglandins, monohydroxys, leukotrienes and epoxyeicosanoids respectively. Through the cytochrome P450 pathway, arachidonic acid can be converted to two kinds of eicosanoid acids: epoxyeicosanoids acid (EET) by cytochrome P450 and hydroxyeicosatetraenoic acids (HETEs) formed by CYP α-oxidases.

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Section: Introductioncontrasting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Soluble Epoxide Hydrolase: Potential Target for Inflammation and Inflammation-Driven Cancer

Lou¹,

Zhang²,

Wang³

et al. 2017

J Carcinog Mutagen

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“…Indeed, Gross et al (5) reported no differences in heart rate and blood pressure at 30 min of occlusion and 2 h of reperfusion in a rat model of regional myocardial I/R in between groups tested with a similar dose of 14,15-EET. In contrast to regional myocardial ischemia, where sEHKO mice are protected, in cardiac arrest-induced whole body ischemia, sEHKO mice were at a disadvantage, presumably due to excessive vasodilation and an inability to maintain blood pressure after cardiopulmonary resuscitation (6).…”

Section: Discussionmentioning

confidence: 96%

Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo

Motoki¹,

Merkel²,

Packwood³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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to dihydroxyeicosatrienoic acids. EETs are formed from arachidonic acid during myocardial ischemia and play a protective role against ischemic cell death. Deletion of sEH has been shown to be protective against myocardial ischemia in the isolated heart preparation. We tested the hypothesis that sEH inactivation by targeted gene deletion or pharmacological inhibition reduces infarct size (I) after regional myocardial ischemia-reperfusion injury in vivo. Male C57BL‫6گ‬J wildtype or sEH knockout mice were subjected to 40 min of left coronary artery (LCA) occlusion and 2 h of reperfusion. Wild-type mice were injected intraperitoneally with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester (AUDA-BE), a sEH inhibitor, 30 min before LCA occlusion or during ischemia 10 min before reperfusion. 14,15-EET, the main substrate for sEH, was administered intravenously 15 min before LCA occlusion or during ischemia 5 min before reperfusion. The EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE) was given intravenously 15 min before reperfusion. Area at risk (AAR) and I were assessed using fluorescent microspheres and triphenyltetrazolium chloride, and I was expressed as I/AAR. I was significantly reduced in animals treated with AUDA-BE or 14,15-EET, independent of the time of administration. The cardioprotective effect of AUDA-BE was abolished by the EET antagonist 14,15-EEZE. Immunohistochemistry revealed abundant sEH protein expression in left ventricular tissue. Strategies to increase 14,15-EET, including sEH inactivation, may represent a novel therapeutic approach for cardioprotection against myocardial ischemia-reperfusion injury.14,15-epoxyeicosatrienoic acids; 12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester THE P-450 EPOXYGENASE PATHWAY metabolizes arachidonic acid into four biologically active eicosanoids, referred to as epoxyeicosatrienoic acids (5,6-, 8,9-, 11,12-, and 14,15-EET) (10). EETs play an important role in regulating tissue perfusion in both cardiac and extracardiac organs. The actions of EETs are terminated by conversion to dihydroxyeicosatrienoic acids (DHETs) by epoxide hydrolases (11). Two major epoxide hydrolases are found in mammalian tissues, the microsomal (mEH) and soluble epoxide hydrolases (sEH) (2). However, sEH is the primary enzyme involved in the in vivo metabolism of EETs (19). In addition to their vascular effects, EETs exhibit a cardioprotective effect, which has been linked to activation of the reperfusion injury salvage kinase pathway (18) and mediated in part through activation of the phosphatidylinositol 3-kinase/Akt pathway and the mitochondrial ATP-sensitive K ϩ channels (5, 15). Augmenting endogenously released EETs by inhibiting the converting enzyme sEH represents an attractive strategy to increase ischemic tolerance. Our laboratory has recently used this strategy to show that pharmacological inhibition (20) and gene deletion (21) are protective against experimental stroke in vivo. Similarly, using the isolated heart preparation, Seubert et al. (16) demonstrat...

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“…CA/CPR is an established model of renal ischemia-reperfusion injury (7,17,18,20). Although the most extensive in vivo findings about renal ischemia have been derived from focal renal pedicle occlusion models, most human AKI occurs after whole body ischemia-reperfusion (25,46).…”

Section: Discussionmentioning

confidence: 99%

“…We performed normothermic CA/CPR as previously described (17,18,20). Briefly, after weighing, general anesthesia was induced with 4% isoflurane in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo

Hutchens

Fujiyoshi

Komers

et al. 2012

American Journal of Physiology-Renal Physiology

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119

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Hutchens MP, Fujiyoshi T, Komers R, Herson PS, Anderson S.Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo. Am J Physiol Renal Physiol 303: F377-F385, 2012. First published May 23, 2012 doi:10.1152/ajprenal.00354.2011.-Emerging evidence suggests that renal endothelial function may be altered in ischemia-reperfusion injury. Acute kidney injury is sexually dimorphic, and estrogen protects renal tubular function after experimental ischemic injury. This study tested the hypothesis that during ischemiareperfusion, estrogen alters glomerular endothelial function to prevent hyperpermeability. Glomerular endothelial cells were exposed to 8-h oxygen-glucose deprivation (OGD) followed by 4-and 8-h reoxygenation-glucose repletion. After 4-h reoxygenation-glucose repletion, transendothelial permeability to Ficoll-70 was reduced, and transendothelial resistance increased, by 17␤-estradiol vs. vehicle treatment during OGD (OGD-vehicle: 91.0 Ϯ 11.8%, OGD-estrogen: 102.6 Ϯ 10.8%, P Ͻ 0.05). This effect was reversed by coadministration of G protein-coupled receptor 30 (GPR30) antagonist G15 with 17␤-estradiol (OGD-estrogen-G15: 89.5 Ϯ 6.9, P Ͻ 0.05 compared with 17␤-estradiol). To provide preliminary confirmation of this result in vivo, Ficoll-70 was administered to mice 24 h after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Blood urea nitrogen (BUN) and serum creatinine (SCr) in these mice were elevated within 12 h following CA/CPR and reduced at 24 h by pretreatment with 17␤-estradiol (BUN/SCr 17␤-estradiol: 34 Ϯ 19/0.2 Ϯ 0.1 vehicle: 92 Ϯ 49/0.5 Ϯ 0.3, n ϭ 8 -12, P Ͻ 0.05). Glomerular sieving of Ficoll 70 was increased by CA/CPR within 2 h of injury and 17␤-estradiol treatment (; 17␤-estradiol: 0.74 Ϯ 0.26 vs. vehicle: 1.05 Ϯ 0.53, n ϭ 14 -15, P Ͻ 0.05). These results suggest that estrogen reduces postischemic glomerular endothelial hyperpermeability at least in part through GPR30 and that estrogen may regulate post CA/CPR glomerular permeability in a similar fashion in vivo.ischemia-reperfusion injury; renal ischemia; acute renal failure; acute kidney injury; oxygen-glucose deprivation; cardiac arrest; cardiopulmonary resuscitation; gender; sex; estrogen; estradiol ACUTE KIDNEY INJURY (AKI) occurs in 10 -30% of intensive care unit patients. There are few therapeutic options for this disease, which has extremely high mortality (up to 70%) and morbidity, with 10% of AKI patients progressing to dialysis-dependent end-stage renal disease (8,23,26,45,46). AKI is a sexually dimorphic disease, with both incidence and mortality being lower in women compared with men (15,30, 49). Experimental models recapitulate the sexually dimorphic nature of AKI and implicate sex steroids in the sex differences observed, demonstrating that androgens increase and estrogens decrease kidney damage in animal models. Several studies have characterized the effects of sex steroids on AKI in animal models and strongly suggested a protective effect of estrogen, but a detailed understanding ...

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Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation

Cited by 59 publications

References 25 publications

Soluble Epoxide Hydrolase: Potential Target for Inflammation and Inflammation-Driven Cancer

Soluble Epoxide Hydrolase: Potential Target for Inflammation and Inflammation-Driven Cancer

Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo

Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo

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