Korean J Physiol Pharmacol.  2004 Dec;8(6):319-327.

Effect of Defibrotide on Rat Reflux Esophagitis

• Kim HK
• Choi SR
• Choi SJ
• Chio MS
• Shin YK

Abstract

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-1beta, tumor necrosis factor-alpha) production in blood, and intracellular 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 1microM formylmethionylleucylphenylalanine (fMLP) - or 0.1microgram/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-1beta 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-1beta), and intracellular calcium mobilization in PMNs in rats.

Keyword

Defibrotide; Polymorphonuclear leukocyte (PMN); Reflux esophagitis

MeSH Terms

Animals
Calcium
Endothelium
Esophagitis
Esophagitis, Peptic*
Esophagus
Hydrogen Peroxide
Hydrogen-Ion Concentration
Hydroxyl Radical
Interleukin-1beta
Lipid Peroxidation
Mesenteric Artery, Superior
Myristic Acid
N-Formylmethionine Leucyl-Phenylalanine
Necrosis
Neutrophils
Peroxidase
Rats*
Reactive Oxygen Species
Superoxides
Tumor Necrosis Factor-alpha
Calcium
Hydrogen Peroxide
Hydroxyl Radical
Interleukin-1beta
Myristic Acid
N-Formylmethionine Leucyl-Phenylalanine
Peroxidase
Reactive Oxygen Species
Superoxides
Tumor Necrosis Factor-alpha