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Xanthine oxidase inhibition attenuates kupffer cell production of neutrophil chemoattractant following ischemia‐reperfusion in rat liver
Author(s) -
Matsumura Fujio,
Yamaguchi Yasuo,
Goto Mataro,
Ichiguchi Osamu,
Akizuki Eiji,
Matsuda Teishi,
Okabe Kazutoshi,
Liang Jian,
Ohshiro Hajime,
Iwamoto Takeshi,
Yamada Shinwa,
Mori Katsutaka,
Ogawa Michio
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280618
Subject(s) - xanthine oxidase , kupffer cell , heparin , reperfusion injury , medicine , pharmacology , ischemia , chemistry , endocrinology , biology , biochemistry , enzyme
We investigated the effects of the xanthine oxidase inhibitor, BOF‐4272, on the production of cytokine‐induced neutrophil chemoattractant (CINC) following reperfusion injury in rat liver. Ischemia was induced for 30 minutes by portal vein occlusion. Animals were pretreated with intravenous injection of BOF‐4272 (1 mg/kg) or heparin (50 U/kg) 5 minutes before vascular clamp. Both BOF‐4272 and heparin limited increases in the chemoattractant compared with nonpretreated rats. Pretreatment with BOF‐4272 plus heparin resulted in an additive effect. Most cells immunostained for chemoattractant were macrophages in sinusoids. In vitro chemoattractant production by Kupffer cells isolated from animals pretreated with heparin or BOF‐4272 was significantly lower than by Kupffer cells from nonpretreated animals. Expression of transcripts in liver for chemoattractant peaked 3 hours after reperfusion in nonpretreated animals, while pretreatment with heparin or BOF‐4272 significantly decreased chemoattractant mRNA levels. In vitro chemoattractant transcription and production could be induced in naive Kupffer cells by hypoxanthine and xanthine oxidase, but BOF‐4272 prevented these increases. We conclude that Kupffer cells release chemoattractant in response to oxygen radicals reducible by xanthine oxidase inhibition.