ArticlePloS one2016
Renal Ischemia/Reperfusion Injury in Soluble Epoxide Hydrolase-Deficient Mice.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Molecular mechanisms of acute inflammation: systemic responses and kidney-specific pathophysiology.Function (Oxford, England) · 2026Review
- Arachidonic acid metabolism as a therapeutic target in AKI-to-CKD transition.Frontiers in pharmacology · 2024Review
- Regulation of soluble epoxide hydrolase in renal-associated diseases: insights from potential mechanisms to clinical researches.Frontiers in endocrinology · 2024Review
- Knock-in mice expressing a humanized arachidonic acid 15-lipoxygenase (Alox15) carry a partly dysfunctional erythropoietic system.Cellular & molecular biology letters · 2023Article
- Humanization of the Reaction Specificity of Mouse Alox15b Inversely Modified the Susceptibility of Corresponding Knock-In Mice in Two Different Animal Inflammation Models.International journal of molecular sciences · 2023Article
- Epoxyeicosatrienoic acid administration or soluble epoxide hydrolase inhibition attenuates renal fibrogenesis in obstructive nephropathy.American journal of physiology. Renal physiology · 2023Article
- Orally active epoxyeicosatrienoic acid analogs in hypertension and renal injury.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Identifying the molecular mechanisms of sepsis-associated acute kidney injury and predicting potential drugs.Frontiers in genetics · 2022Article
- Arachidonic Acid Metabolism and Kidney Inflammation.International journal of molecular sciences · 2019Review
- Prophylactic inhibition of soluble epoxide hydrolase delays onset of nephritis and ameliorates kidney damage in NZB/W F1 mice.Scientific reports · 2019Article
- Chiral lipidomics of monoepoxy and monohydroxy metabolites derived from long-chain polyunsaturated fatty acids.Journal of lipid research · 2019Article
- Prospective for cytochrome P450 epoxygenase cardiovascular and renal therapeutics.Pharmacology & therapeutics · 2018Review
- Effect of Soluble Epoxide Hydrolase in Hyperoxic Acute Lung Injury in Mice.Inflammation · 2018Article
- Inhibition of Soluble Epoxide Hydrolase 2 Ameliorates Diabetic Keratopathy and Impaired Wound Healing in Mouse Corneas.Diabetes · 2018Article
- Blockade of soluble epoxide hydrolase attenuates post-ischemic neuronal hyperexcitation and confers resilience against stroke with TrkB activation.Scientific reports · 2018Article
- Inhibition of Soluble Epoxide Hydrolase for Renal Health.Frontiers in pharmacology · 2018Review
- Epoxide metabolites of arachidonate and docosahexaenoate function conversely in acute kidney injury involved in GSK3β signaling.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Beyond detoxification: a role for mouse mEH in the hepatic metabolism of endogenous lipids.Archives of toxicology · 2017Article
- Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology.Journal of the American Society of Nephrology : JASN · 2017Review
- Pharmacological Inhibition of PTEN Aggravates Acute Kidney Injury.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aim20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP)-dependent eicosanoids that play opposite roles in the regulation of vascular tone, inflammation, and apoptosis. 20-HETE aggravates, whereas EETs ameliorate ischemia/reperfusion (I/R)-induced organ damage. EETs are rapidly metabolized to dihydroxyeicosatrienoic acids (DHETs) by the soluble epoxide hydrolase (sEH). We hypothesized that sEH gene (EPHX2) deletion would increase endogenous EET levels and thereby protect against I/R-induced acute kidney injury (AKI).
methodsKidney damage was evaluated in male wildtype (WT) and sEH-knockout (KO)-mice that underwent 22-min renal ischemia followed by two days of reperfusion. CYP-eicosanoids were analyzed by liquid chromatography tandem mass spectrometry.
resultsContrary to our initial hypothesis, renal function declined more severely in sEH-KO mice as indicated by higher serum creatinine and urea levels. The sEH-KO-mice also featured stronger tubular lesion scores, tubular apoptosis, and inflammatory cell infiltration. Plasma and renal EET/DHET-ratios were higher in sEH-KO than WT mice, thus confirming the expected metabolic consequences of sEH deficiency. However, CYP-eicosanoid profiling also revealed that renal, but not plasma and hepatic, 20-HETE levels were significantly increased in sEH-KO compared to WT mice. In line with this finding, renal expression of Cyp4a12a, the murine 20-HETE-generating CYP-enzyme, was up-regulated both at the mRNA and protein level, and Cyp4a12a immunostaining was more intense in the renal arterioles of sEH-KO compared with WT mice.
conclusionThese results indicate that the potential beneficial effects of reducing EET degradation were obliterated by a thus far unknown mechanism leading to kidney-specific up-regulation of 20-HETE formation in sEH-KO-mice.
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