Pregled bibliografske jedinice broj: 677915
Beneficial effects of a new 20-hydroxyeicosatetraenoic acid synthesis inhibitor, TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], on hemorrhagic and ischemic stroke
Beneficial effects of a new 20-hydroxyeicosatetraenoic acid synthesis inhibitor, TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], on hemorrhagic and ischemic stroke // The Journal of pharmacology and experimental therapeutics, 314 (2005), 1; 77-85 doi:10.1124/jpet.105.083964 (međunarodna recenzija, članak, znanstveni)
CROSBI ID: 677915 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Beneficial effects of a new 20-hydroxyeicosatetraenoic acid synthesis inhibitor, TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], on hemorrhagic and ischemic stroke
Autori
Miyata, N. ; Seki, T. ; Tanaka, Y. ; Omura, T. ; Taniguchi, K. ; Doi, M. ; Bandou, K. ; Kametani, S. ; Sato, M. ; Okuyama, S. ; Cambj-Sapunar, Liana ; Harder, D.R. ; Roman R.J.
Izvornik
The Journal of pharmacology and experimental therapeutics (0022-3565) 314
(2005), 1;
77-85
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni
Sažetak
The present study characterized the effects of TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N′-hydroxyimido formamide], a new selective inhibitor of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), on the metabolism of arachidonic acid by human and rat renal microsomes and the inhibitory effects of this compound on hepatic cytochrome P450 enzymes involved in drug metabolism. The effects of TS-011 on the fall in cerebral blood flow following subarachnoid hemorrhage (SAH) and in reducing infarct size in ischemic stroke models were also examined since 20-HETE may contribute to the development of cerebral vasospasm. TS-011 inhibited the synthesis of 20-HETE by human renal microsomes and recombinant CYP4A11 and 4F2, 4F3A, and 4F3B enzymes with IC50 values around 10 to 50 nM. It had no effect on the activities of CYP1A, 2C9, 2C19, 2D6, or 3A4 enzymes. TS-011 inhibited the synthesis of 20-HETE by rat renal microsomes with an IC50 of 9.19 nM, and it had no effect on epoxygenase activity at a concentration of 100 μM. TS-011 (0.01–1 mg/kg i.v.) reversed the fall in cerebral blood flow and the increase in 20-HETE levels in the cerebrospinal fluid of rats after SAH. TS-011 also reduced the infarct volume by 35% following transient ischemic stroke and in intracerebral hemorrhage in rats. Injection of 20-HETE (8 or 12 mg/kg) into the carotid artery produced an infarct similar to that seen in the ischemic stroke model. These studies indicate that blockade of the synthesis of 20-HETE with TS-011 opposes cerebral vasospasm following SAH and reduces infarct size in ischemic models of stroke.
Izvorni jezik
Engleski
Znanstvena područja
Temeljne medicinske znanosti
POVEZANOST RADA
Projekti:
216-2160528-0506 - Trombolitičko liječenje ishemijskog moždanog udara na štakorskim modelima (Cambj Sapunar, Liana, MZOS ) ( CroRIS)
Ustanove:
Medicinski fakultet, Split
Profili:
Liana Cambj Sapunar
(autor)
Citiraj ovu publikaciju:
Časopis indeksira:
- Current Contents Connect (CCC)
- Web of Science Core Collection (WoSCC)
- Science Citation Index Expanded (SCI-EXP)
- SCI-EXP, SSCI i/ili A&HCI
- Scopus
- MEDLINE