Prevention of impaired liver metabolism due to ischemia in rats. Efficacy of defibrotide administration.

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.