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Titolo:
Attenuation of ischemia and reperfusion injury of canine livers by inhibition of type II phospholipase A(2) with LY329722
Autore:
Ogata, K; Jin, MB; Taniguchi, M; Suzuki, T; Shimamura, T; Kitagawa, N; Magata, S; Fukai, M; Ishikawa, H; Ono, T; Furukawa, H; Fujita, M; Todo, S;
Indirizzi:
Hokkaido Univ, Sch Med, Dept Surg 1, Kita Ku, Sapporo, Hokkaido 0608638, Japan Hokkaido Univ Sapporo Hokkaido Japan 0608638 oro, Hokkaido 0608638, Japan Hokkaido Univ, Sch Med, Dept Pathol 2, Sapporo, Hokkaido 0608638, Japan Hokkaido Univ Sapporo Hokkaido Japan 0608638 oro, Hokkaido 0608638, Japan Shionogi Res Labs, Osaka 5330002, Japan Shionogi Res Labs Osaka Japan 5330002 ogi Res Labs, Osaka 5330002, Japan
Titolo Testata:
TRANSPLANTATION
fascicolo: 8, volume: 71, anno: 2001,
pagine: 1040 - 1046
SICI:
0041-1337(20010427)71:8<1040:AOIARI>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLATELET-ACTIVATING-FACTOR; THROMBOXANE A(2); RAT-LIVER; COLD ISCHEMIA; CELLS; NEUTROPHILS; TRANSPLANTATION; INFILTRATION; METABOLITES; RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Todo, S Hokkaido Univ, Sch Med, Dept Surg 1, Kita Ku, N-15,W-7, Sapporo, Hokkaido 0608638, Japan Hokkaido Univ N-15,W-7 Sapporo Hokkaido Japan 0608638 08638, Japan
Citazione:
K. Ogata et al., "Attenuation of ischemia and reperfusion injury of canine livers by inhibition of type II phospholipase A(2) with LY329722", TRANSPLANT, 71(8), 2001, pp. 1040-1046

Abstract

Background. Membrane phospholipid breakdown, caused by ischemia and reperfusion (I/R) of the liver, releases free fatty acids including arachidonic acids and lysophospholipids, which serve as precursors of various inflammatory lipid derivatives. Phospholipase A(2) (PLA(2)) is a key enzyme that initiates this reaction. In this study, we tested our hypothesis that a type IIPLA(2) inhibitor, LY329722, could attenuate hepatic YR injury caused by a 2-hr total hepatic vascular exclusion (THVE) in dogs. Methods. Eighteen beagle dogs, subjected to a 2-hr THVE, were divided intothree groups. Group 1 (n=6) was untreated and served as a control group. LY329722 was administered to animals in group 2 (n=6) intravenously (0.2 mg.kg(-1).hr(-1)) for 60 min before ischemia, and to animals in group 3 (n=6) for 60 min starting 15 min before reperfusion (0.2 mg.kg(-1).hr(-1)). Animal survival, systemic and splanchnic hemodynamics, hepatic tissue blood flow, liver functions, energy metabolism, hepatic venous thromboxane B, and endothelin-1 levels, phospholipid levels and tumor necrosis factor-alpha mRNA expression in liver tissue, and histopathologic findings were evaluated. Results. Two-week animal survival was 33% (two of six) in group 1, and 100% (six of six) in groups 2 and 3. LY329722 improved systemic and splanchnichemodynamics, hepatic tissue blood flow, and energy metabolism, reduced liver enzyme, thromboxane B-2, and endothelin-1 release, prevented hepatic phospholipid degradation and tumor necrosis factor-alpha mRNA expression, andlessened histopathologic damage and the number of neutrophil infiltrating into the liver tissue. Conclusion. The present study demonstrated that a type II PLA, inhibitor, LY329722, attenuated hepatic I/R injury caused by a 2-hr THVE model in dogs.

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Documento generato il 31/03/20 alle ore 04:30:39