Korean J Physiol Pharmacol.  2006 Apr;10(2):85-94.

Protective Effect of Defibrotide on Splanchnic Injury following Ischemia and Reperfusion in Rats

• Choi SR
• Jeong JH
• Song JH
• Shin YK

Abstract

A splanchic artery occlusion for 90 min followed by reperfusion of the mesenteric circulation resulted in a severe form of circulatory shock, characterized by endothelial dysfunction, severe hypotension, marked intestinal tissue injury, and a high mortality rate. The effect of defibrotide, a complex of single-stranded polydeoxyribonucleotides having antithrombotic effect, was investigated in a model of splanchnic artery occlusion (SAO) shock in urethane anesthetized rats. Occlusion of the superior mesenteric artery for 90 min produced a severe shock state, resulting in a fatal outcome within 120 min of reperfusion in many rats. Defibrotide (10 mg/kg body weight) 10 min prior to reperfusion significantly improved mean arterial blood pressure in comparison to vehicle treated rats (p<0.05). Defibrotide treatment also significantly attenuated in the increase of plasma amino nitrogen concentration, intestinal myeloperoxidase activity, intestinal lipid peroxidation, infiltration of neutrophils in intestine and thrombin induced adherence of neutrophils to superior mesentric artery segments. Superoxide anion and hydrogen peroxide production in 1 micrometer formylmethionylleucylphenylalanine (fMLP)-activated PMNs was inhibited by defibrotide in a dose-dependent fashion. Defibrotide effectively scavenged hydrogen peroxide, but not hydroxyl radical. Treatment of SAO rats with defibrotide inhibited tumor necrosis factor-alpha, and interleukin-1beta productions in blood in comparison with untreated rats. These results suggest that defibrotide partly provides beneficial effects by preserving endothelial function, attenuating neutrophil accumulation, and antioxidant in the ischemic reperfused splanchnic circulation.

Keyword

Defibrotide; Ischemia; Reperfusion

MeSH Terms

Animals
Arterial Pressure
Arteries
Fatal Outcome
Hydrogen Peroxide
Hydroxyl Radical
Hypotension
Interleukin-1beta
Intestines
Ischemia*
Lipid Peroxidation
Mesenteric Artery, Superior
Mortality
N-Formylmethionine Leucyl-Phenylalanine
Neutrophils
Nitrogen
Peroxidase
Plasma
Polydeoxyribonucleotides
Rats*
Reperfusion*
Shock
Splanchnic Circulation
Superoxides
Thrombin
Tumor Necrosis Factor-alpha
Urethane
Hydrogen Peroxide
Hydroxyl Radical
Interleukin-1beta
N-Formylmethionine Leucyl-Phenylalanine
Nitrogen
Peroxidase
Polydeoxyribonucleotides
Superoxides
Thrombin
Tumor Necrosis Factor-alpha
Urethane