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Original Paper

Effects of Selective Cyclooxygenase Inhibitors on Ischemia/Reperfusion-Induced Hepatic Microcirculatory Dysfunction in Mice

Ito Y.a · Katagiri H.a · Ishii K.a · Kakita A.a · Hayashi I.b · Majima M.b

Author affiliations

Departments of aSurgery and bPharmacology, Kitasato University School of Medicine, Sagamihara, Japan

Related Articles for ""

Eur Surg Res 2003;35:408–416

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 01, 2002
Accepted: January 30, 2003
Published online: August 28, 2003
Issue release date: September – October

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0

ISSN: 0014-312X (Print)
eISSN: 1421-9921 (Online)

For additional information: http://www.karger.com/ESR

Abstract

We examined the effects of selective cyclooxygenase (COX) inhibition on hepatic warm ischemia/reperfusion (I/R) injury in mice. A selective COX-1 inhibitor, SC-560, selective COX-2 inhibitors, NS-398 and celecoxib, and indomethacin were administered 30 min before ischemia. Four hours after reperfusion, an in vivo microscopic study showed that I/R caused significant accumulation of leukocytes adhering to the hepatic microvessels and nonperfused sinusoids. Levels of plasma alanine transaminase (ALT) and tumor necrosis factor (TNF)-α also showed increases. SC-560, NS-398, celecoxib and indomethacin significantly reduced hepatic responses to I/R including microcirculatory dysfunction and release of ALT and TNF-α. Moreover, the effects of the thromboxane (TX) A2 (TXA2) synthase inhibitor OKY-046 and the TXA2 receptor antagonist S-1452 on hepatic responses to I/R exhibited results similar to those obtained with COX inhibitors. These results suggest that COX-1 and COX-2 contribute to I/R-induced hepatic microvascular and hepatocellular injury partly through TNF-α production, and that TXs derived from COX are partly responsible for I/R-induced liver injury.

© 2003 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 01, 2002
Accepted: January 30, 2003
Published online: August 28, 2003
Issue release date: September – October

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0

ISSN: 0014-312X (Print)
eISSN: 1421-9921 (Online)

For additional information: http://www.karger.com/ESR


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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