Prilog u časopisu
Hyperbaric Oxygenation and 20-hydroxyeicosatetreanoic acid Inhibition Reduce Stroke Volume in Female Diabetic Sprague-Dawley rats
Mišir, Mihael ; Renić, Marija ; Novak, Sanja ; Mihalj, Martina ; Ćosić, Anita ; Vesel, Monika ; Drenjančević, Ines
2017.
izvorni znanstveni rad
What is the central question of this study? Is there a beneficial effect and what are the mechanisms of acute and multiple hyperbaric oxygenation (HBO2 ) exposures on the outcome of cerebral tissue injury induced by a transient middle cerebral artery occlusion model in diabetic female rats? Are 20-hydroxyeicosatetreanoic acid and epoxyeicosatrienoic acids involved? What is the main finding and its importance? Equal reduction of cortical and total infarct size in rats treated with HBO2 and HET0016 (20-hydroxyeicosatetreanoic acid production inhibitor) and significant mRNA upregulation of epoxyeicosatrienoic acid-producing enzymes (Cyp2J3 and Cyp2C11) in treated groups suggest that HBO2 and HET0016 are highly effective stroke treatments and that cytochrome P450 metabolites are involved in this therapeutic effect. We evaluated the effects of acute and repetitive hyperbaric oxygenation (HBO2 ), 20-hydroxyeicosatetreanoic acid (20-HETE) inhibition by N-hydroxy-N'-(4-butyl-2methylphenyl)-formamidine (HET0016) and their combination on experimental stroke outcomes. Streptozotocin-induced type 1 diabetic Sprague-Dawley female rats (n = 42; n = 7 per group), were subjected to 30 min of transient middle cerebral artery occlusion (t-MCAO)-reperfusion and divided into the following groups: (1) control group, without treatment; and groups exposed to: (2) HBO2 ; (3) multiple HBO2 (HBO2 immediately and second exposure 12 h after t-MCAO); (4) HET0016 pretreatment (1 mg kg-1 , 3 days before t-MCAO) combined with HBO2 after t-MCAO; (5) HET0016 treatment (1 h before, during and for 6 h after t-MCAO); and (6) HET0016 treatment followed by HBO2 after t-MCAO. Messenger RNA expression of CYP2J3, CYP2C11, CYP4A1, endothelial nitric oxide synthase and epoxide hydrolase 2 was determined by real-time qPCR. Cortical infarct size and total infarct size were equally and significantly reduced in HBO2 - and HET0016-treated rats. Combined treatment with HET0016 and HBO2 provided no significant additive effect compared with HET0016 treatment only. Messenger RNA of Cyp2J3 was significantly increased in all study groups, and mRNA of Cyp2C11 was significantly increased in the multiple HBO2 group and the HET0016 treatment followed by HBO2 group, compared with the control group. Expression of endothelial nitric oxide synthase was significantly increased after HBO2 treatments, and expression of epoxide hydrolase 2 was increased in all groups compared with the control group. In diabetic female Sprague-Dawley rats, HBO2 and HET0016 are highly effective stroke treatments, suggesting the involvement of cytochrome P450 metabolites and the NO pathway in this therapeutic effect.
Amidines/pharmacology Animals Aryl Hydrocarbon Hydroxylases/genetics Aryl Hydrocarbon Hydroxylases/metabolism Brain/drug effects Brain/metabolism Brain/pathology Combined Modality Therapy Diabetes Mellitus, Experimental/metabolism Diabetes Mellitus, Experimental/physiopathology Diabetes Mellitus, Experimental/therapy Epoxide Hydrolases/genetics Epoxide Hydrolases/metabolism Female Gene Expression Regulation, Enzymologic Hyperbaric Oxygenation Infarction, Middle Cerebral Artery/metabolism Infarction, Middle Cerebral Artery/pathology Rats, Sprague-Dawley Reperfusion Injury/metabolism Reperfusion Injury/pathology Reperfusion Injury/physiopathology Time Factors
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Vrsta sadržaja: text
Jezik sadržaja: engleski
Otvoreni pristup
Autori Mišir, Mihael (Autor) (mbz: 357666) ; Renić, Marija (Autor) (mbz: 194961) ; Novak, Sanja (Autor) (mbz: 326355) ; Mihalj, Martina (Autor) (mbz: 322792) ; Ćosić, Anita (Autor) ; Vesel, Monika (Autor) ; Drenjančević, Ines (Autor) (mbz: 209603)
Studijski program
Nema podataka
Umjetnička i znanstvena područja, polja i grane
Biomedicina i zdravstvo / Kliničke medicinske znanosti / interna medicina
Datumi
Datum objave publikacije: 2017.
URL-ovi
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/EP086402
Jezici
engleski
Institucije
Sveučilište Josipa Jurja Strossmayera u Osijeku, Sveučilište Josipa Jurja Strossmayera u Osijeku, Medicinski fakultet Osijek
Sveučilište u Zagrebu, Sveučilište u Zagrebu, Medicinski fakultet
Status publikacije
objavljen
Datum izrade zapisa
20.01.2020.
Broj posjeta
0
Broj preuzimanja
0
Identifikatori
DOI: 10.1113/EP086402
URN:NBN: https://urn.nsk.hr/urn:nbn:hr:239:159599
Publikacija
pISSN: 0958-0670
eISSN: 1469-445X
Broj: 102
Sveščić: 12
Početna stranica: 1596
Zadnja stranica: 1606