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The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology v.8 no.6, 2004년, pp.319 - 327  
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Effect of Defibrotide on Rat Reflux Esophagitis

Kim, Hyoung-Ki    (Department of Pharmacology, College of Medicine, Chung-Ang University   ); Choi, Soo-Ran    (Department of Pharmacology, College of Medicine, Chung-Ang University   ); Choi, Sang-Jin    (Department of Pharmacology, College of Medicine, Chung-Ang University   ); Chio, Myung-Sup    (Department of Pharmacology, College of Medicine, Chung-Ang University   ); Shin, Yong-Kyoo    (Department of Pharmacology, College of Medicine, Chung-Ang University  );
  • 초록

    This study was aimed at evaluating the effect of defibrotide on the development of the surgically induced reflux esophagitis, on gastric secretion, lipid peroxidation, polymorphonuclear leukocytes (PMNs) accumulation, polymorphonuclear leukocytes adherence, superoxide anion and hydrogen peroxide production in PMNs, scavenge of hydroxyl radical and hydrogen peroxide, cytokine (interleukin-1 ${\beta}$ , tumor necrosis $factor-{\alpha}$ ) production in blood, and intracelluar calcium mobilization in PMNs. Defibrotide did not inhibit the gastric secretion and not change the gastric pH. Treatment of esophagitis rats with defibrotide inhibited lipid peroxidation, and myeloperoxidase (MPO) in the esophagus in comparison with untreated rats. Defibrotide significantly decreased the PMN adherence to superior mesenteric artery endothelium in a dose-dependent manner, Superoxide anion and hydrogen peroxide production in $1{\mu}M$ formylmethionylleucylphenylalanine (fMLP)- or $0.1{\mu}g/ml$ N-phorbol 12-myristate 13-acetate (PMA)-activated PMNs was inhibited by defibrotide in a dose-dependent fashion. Defibrotide effectively scavenged the hydrogen peroxide but did not scavenge the hydroxyl radical. Treatment of esophagitis rats with defibrotide inhibited interleukin-1 ${\beta}$ production in the blood in comparison with untreated rats, but tumor necrosis $factor-{\alpha}$ production was not affected by defibrotide. The fMLP-induced elevation of intracellular calcium in PMNs was inhibited by defibrotide. The results of this study suggest that defibrotide may have partly beneficial protective effects against reflux esophagitis by the inhibition lipid peroxidation, PMNs accumulation, PMNs adherence to endothelium, reactive oxygen species production in PMNs, inflammatory cytokine production(i.e. interleukin-1 ${\beta}$ ), and intracellular calcium mobilization in PMNs in rats.


  • 주제어

    Defibrotide .   Polymorphonuclear leukocyte (PMN) .   Reflux esophagitis.  

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