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Involvement of renal cytochromes P450 and arachidonic acid metabolites in diabetic nephropathy

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dc.contributor.author Eid S.
dc.contributor.author Abou-Kheir W.
dc.contributor.author Sabra R.
dc.contributor.author Daoud G.
dc.contributor.author Jaffa A.
dc.contributor.author Ziyadeh F.N.
dc.contributor.author Roman L.
dc.contributor.author Eid A.A.
dc.contributor.editor
dc.date Jul-2013
dc.date.accessioned 2017-10-05T16:02:44Z
dc.date.available 2017-10-05T16:02:44Z
dc.date.issued 2013
dc.identifier
dc.identifier.isbn
dc.identifier.issn
dc.identifier.uri http://hdl.handle.net/10938/19605
dc.description.abstract Diabetic nephropathy (DN) is one of the most serious complications of type I and type II diabetes. DN is characterized by hyperfiltration, hypertrophy, extracellular matrix accumulation, and proteinuria. This advances into renal fibrosis and loss of renal function. Reactive oxygen species (ROS) and TGF-β have been implicated in the pathogenesis of diabetic nephropathy. Early stages of diabetic nephropathy are also associated with alterations in renal sodium handling as well as hypertension; both are processes linked by involvement of the arachidonic acid (AA) metabolites, 20-hydroxyeicosatetraenoic acid (20-HETE, produced by cytochrome P450-4a, (CYP4A) and epoxyeicosatrienoic acids (EETs). Indeed, metabolism of AA is increased in a rat model of diabetes. In this study, we demonstrate that rats with streptozotocin-induced diabetes of 1 month duration develop renal hypertrophy and increased fibronectin and TGF-β1 expression-cortical levels concomitant with an increase in CYP4A expression and 20 HETE production. These results were also paralleled by an increase in reactive oxygen species (ROS) production and NADPH oxidase activity. Treatment of diabetic rats with HET0016, selective inhibitor of CYP4A, prevented all these changes. Our results suggest that diabetes-induced induction of CYP4A and 20-HETE production could be a major pathophysiological mechanism leading to activation of ROS through an NADPH dependent pathway and TGF-β1 thus resulting in major renal pathology. Inhibitors of 20-HETE production could thus have an important therapeutic potential in the treatment of diabetic nephropathy. Copyright © by BIOLIFE, s.a.s.
dc.format.extent
dc.format.extent Pages: (693-703)
dc.language English
dc.publisher Biolife; SILVA MARINA (TE)
dc.relation.ispartof Publication Name: Journal of Biological Regulators and Homeostatic Agents; Publication Year: 2013; Volume: 27; no. 3; Pages: (693-703);
dc.relation.ispartofseries
dc.relation.uri
dc.source Scopus
dc.subject.other
dc.title Involvement of renal cytochromes P450 and arachidonic acid metabolites in diabetic nephropathy
dc.type Article
dc.contributor.affiliation Eid, S., American University of Beirut, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, P.O. Box: 11-0236 Riad El Solh 1107, 2020, Beirut, Lebanon
dc.contributor.affiliation Abou-Kheir, W., American University of Beirut, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, P.O. Box: 11-0236 Riad El Solh 1107, 2020, Beirut, Lebanon
dc.contributor.affiliation Sabra, R., Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Lebanon
dc.contributor.affiliation Daoud, G., American University of Beirut, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, P.O. Box: 11-0236 Riad El Solh 1107, 2020, Beirut, Lebanon
dc.contributor.affiliation Jaffa, A., Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Lebanon
dc.contributor.affiliation Ziyadeh, F.N., Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Lebanon
dc.contributor.affiliation Roman, L., Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio TX, United States
dc.contributor.affiliation Eid, A.A., American University of Beirut, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, P.O. Box: 11-0236 Riad El Solh 1107, 2020, Beirut, Lebanon
dc.contributor.authorAddress Eid, A.A.; American University of Beirut, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, P.O. Box: 11-0236 Riad El Solh 1107, 2020, Beirut, Lebanon; email: ae49@aub.edu.lb
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Pharmacology and Toxicology;
dc.contributor.authorDepartment Pharmacology and Toxicology
dc.contributor.authorDivision
dc.contributor.authorEmail ae49@aub.edu.lb
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials Eid, S
dc.contributor.authorInitials Abou-Kheir, W
dc.contributor.authorInitials Sabra, R
dc.contributor.authorInitials Daoud, G
dc.contributor.authorInitials Jaffa, A
dc.contributor.authorInitials Ziyadeh, FN
dc.contributor.authorInitials Roman, L
dc.contributor.authorInitials Eid, AA
dc.contributor.authorOrcidID
dc.contributor.authorReprintAddress Eid, AA (reprint author), Amer Univ Beirut, Dept Anat Cell Biol and Physiol, Fac Med, POB 11-0236,Riad El Solh 1107, Beirut 2020, Lebanon.
dc.contributor.authorResearcherID
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.description.citedCount 1
dc.description.citedTotWOSCount 2
dc.description.citedWOSCount 2
dc.format.extentCount 11
dc.identifier.articleNo
dc.identifier.coden JBRAE
dc.identifier.pubmedID 24152838
dc.identifier.scopusID 84891604983
dc.identifier.url
dc.publisher.address VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY
dc.relation.ispartofConference
dc.relation.ispartofConferenceCode
dc.relation.ispartofConferenceDate
dc.relation.ispartofConferenceHosting
dc.relation.ispartofConferenceLoc
dc.relation.ispartofConferenceSponsor
dc.relation.ispartofConferenceTitle
dc.relation.ispartofFundingAgency
dc.relation.ispartOfISOAbbr J. Biol. Regul. Homeost. Agents
dc.relation.ispartOfIssue 3
dc.relation.ispartOfPart
dc.relation.ispartofPubTitle Journal of Biological Regulators and Homeostatic Agents
dc.relation.ispartofPubTitleAbbr J. Biol. Regul. Homeostatic Agents
dc.relation.ispartOfSpecialIssue
dc.relation.ispartOfSuppl
dc.relation.ispartOfVolume 27
dc.source.ID WOS:000326306600010
dc.type.publication Journal
dc.subject.otherAuthKeyword 20-HETE
dc.subject.otherAuthKeyword Cytochromes P450
dc.subject.otherAuthKeyword Diabetic nephropathy
dc.subject.otherAuthKeyword NADPH oxidase
dc.subject.otherAuthKeyword Reactive oxygen species
dc.subject.otherAuthKeyword TGF-β
dc.subject.otherChemCAS 20 hydroxyicosatetraenoic acid, 79551-86-3
dc.subject.otherChemCAS arachidonic acid, 506-32-1, 6610-25-9, 7771-44-0
dc.subject.otherChemCAS cytochrome P450, 9035-51-2
dc.subject.otherChemCAS epoxyicosatrienoic acid, 97717-69-6
dc.subject.otherChemCAS fibronectin, 86088-83-7
dc.subject.otherChemCAS glucose, 50-99-7, 84778-64-3
dc.subject.otherChemCAS insulin, 9004-10-8
dc.subject.otherChemCAS reduced nicotinamide adenine dinucleotide phosphate oxidase, 9032-22-8
dc.subject.otherChemCAS streptozocin, 18883-66-4
dc.subject.otherChemCAS superoxide, 11062-77-4
dc.subject.otherChemCAS alkane 1 monooxygenase, 9059-16-9
dc.subject.otherChemCAS hydroxyicosatetraenoic acid, 69845-60-9
dc.subject.otherChemCAS 20-hydroxy-5,8,11,14-eicosatetraenoic acid, 79551-86-3
dc.subject.otherChemCAS Alkane 1-Monooxygenase, 1.14.15.3
dc.subject.otherChemCAS Hydroxyeicosatetraenoic Acids
dc.subject.otherChemCAS NADPH Oxidase, 1.6.3.1
dc.subject.otherChemCAS Reactive Oxygen Species
dc.subject.otherChemCAS Streptozocin, 5W494URQ81
dc.subject.otherChemCAS Transforming Growth Factor beta1
dc.subject.otherIndex 20 hydroxyicosatetraenoic acid
dc.subject.otherIndex arachidonic acid
dc.subject.otherIndex cytochrome P450
dc.subject.otherIndex cytochrome P450 4A
dc.subject.otherIndex cytochrome P450 inhibitor
dc.subject.otherIndex epoxyicosatrienoic acid
dc.subject.otherIndex fibronectin
dc.subject.otherIndex glucose
dc.subject.otherIndex het 0016
dc.subject.otherIndex insulin
dc.subject.otherIndex reactive oxygen metabolite
dc.subject.otherIndex reduced nicotinamide adenine dinucleotide phosphate oxidase
dc.subject.otherIndex streptozocin
dc.subject.otherIndex superoxide
dc.subject.otherIndex transforming growth factor beta1
dc.subject.otherIndex unclassified drug
dc.subject.otherIndex 20 hydroxy 5,8,11,14 eicosatetraenoic acid
dc.subject.otherIndex 20-hydroxy-5,8,11,14-eicosatetraenoic acid
dc.subject.otherIndex alkane 1 monooxygenase
dc.subject.otherIndex hydroxyicosatetraenoic acid
dc.subject.otherIndex reactive oxygen metabolite
dc.subject.otherIndex reduced nicotinamide adenine dinucleotide phosphate oxidase
dc.subject.otherIndex transforming growth factor beta1
dc.subject.otherIndex animal experiment
dc.subject.otherIndex animal model
dc.subject.otherIndex animal tissue
dc.subject.otherIndex article
dc.subject.otherIndex body weight
dc.subject.otherIndex controlled study
dc.subject.otherIndex diabetic nephropathy
dc.subject.otherIndex enzyme activity
dc.subject.otherIndex fatty acid metabolism
dc.subject.otherIndex glucose blood level
dc.subject.otherIndex high performance liquid chromatography
dc.subject.otherIndex hyperglycemia
dc.subject.otherIndex hypertension
dc.subject.otherIndex kidney hypertrophy
dc.subject.otherIndex kidney mass
dc.subject.otherIndex kidney microsome
dc.subject.otherIndex male
dc.subject.otherIndex nonhuman
dc.subject.otherIndex pathogenesis
dc.subject.otherIndex protein expression
dc.subject.otherIndex rat
dc.subject.otherIndex streptozotocin-induced diabetes mellitus
dc.subject.otherIndex upregulation
dc.subject.otherIndex animal
dc.subject.otherIndex biosynthesis
dc.subject.otherIndex diabetic nephropathy
dc.subject.otherIndex enzymology
dc.subject.otherIndex experimental diabetes mellitus
dc.subject.otherIndex kidney
dc.subject.otherIndex metabolism
dc.subject.otherIndex pathology
dc.subject.otherIndex physiology
dc.subject.otherIndex Alkane 1-Monooxygenase
dc.subject.otherIndex Animals
dc.subject.otherIndex Diabetes Mellitus, Experimental
dc.subject.otherIndex Diabetic Nephropathies
dc.subject.otherIndex Hydroxyeicosatetraenoic Acids
dc.subject.otherIndex Kidney
dc.subject.otherIndex Male
dc.subject.otherIndex NADPH Oxidase
dc.subject.otherIndex Rats
dc.subject.otherIndex Reactive Oxygen Species
dc.subject.otherIndex Streptozocin
dc.subject.otherIndex Transforming Growth Factor beta1
dc.subject.otherKeywordPlus GROWTH-FACTOR-BETA
dc.subject.otherKeywordPlus SMOOTH-MUSCLE-CELLS
dc.subject.otherKeywordPlus OXIDATIVE STRESS
dc.subject.otherKeywordPlus NADPH OXIDASE
dc.subject.otherKeywordPlus EXPRESSION
dc.subject.otherKeywordPlus 20-HETE
dc.subject.otherKeywordPlus INJURY
dc.subject.otherKeywordPlus PROLIFERATION
dc.subject.otherKeywordPlus COMPLICATIONS
dc.subject.otherKeywordPlus HYPERTROPHY
dc.subject.otherWOS Endocrinology and Metabolism
dc.subject.otherWOS Immunology
dc.subject.otherWOS Medicine, Research and Experimental
dc.subject.otherWOS Physiology


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