title: Prevention of impaired liver metabolism due to ischemia in rats. Efficacy of defibrotide administration.
abstract: The effect of defibrotide treatment in protecting liver metabolism from ischemic damage was studied. The drug was administered to male Wistar rats as a bolus (30 mg/kg body weight) at the beginning of 60 min ischemia and then continuously during 60 min of postischemic reperfusion at a dose of 30 mg/kg body weight. This dose was previously identified as useful to protect against myocardial ischemia induced in the cat. ATP and ADP intrahepatic levels were significantly higher in drug-treated rats than in untreated animals. The liver cytoplasmic NAD+/NADH ratio in defibrotide-treated rats was no different from that observed in sham-operated rats. The mitochondrial NAD+/NADH ratio in the liver was also improved by defibrotide treatment. Our data suggest that defibrotide may exert protective activity on hepatocytes useful for inducing a rapid restoration of their metabolism. Such a restoration is possibly related to improvement of microcirculation through an increase in prostaglandin I2 production or oxygen delivery due to drug administration.
authors.affiliation: Istituto di Patologia Generale, Università di Milano, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Ferrero
authors.forename: A
authors.initials: A
authors.lastname: Marni
authors.forename: G
authors.initials: G
authors.lastname: Gaja
mesh_terms: D000227:Adenine Nucleotides / Q000032:analysis; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy*; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000227:Adenine Nucleotides; D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; D009243:NAD; C036901:defibrotide