Attenuation of ischemic liver injury by prostaglandin E1 analogue, misoprostol, and prostaglandin I2 analogue, OP-41483

Background. Prostaglandins (PG,.;) have protective effects against liver injury However, the use of this agent in clinical settings is limited due to drug-related side effects. This study investigated whether misoprostol, a prostaglandin E-1, analogue, and OP-41483, a prostaglandin I-2, analogue (which have fewer adverse effects with a longer half-life), attenuate ischemic liver damage. Study design. Twenty beagle dogs underwent 2 It of hepatic vascular exclusion using venovenous bypass. Misoprostol was administered intravenously for 30 min before ischemia (15 mug/kg) and for 3 It after reperfusion (35 mug/kg). OP-41483 was administered intraportally for 30 min before ischemia (2 mug/kg/min) and for 3 It after reperfusion (0.5 mug/kg/min). Animals were divided into three groups: untreated control group (n = 10) misoprostol administered group (MP, n = 5); and OP-41483 administered group (OP, n 5). Animal survival, hepatic tissue blood flow, (HTBF), liver enzyme, and histology were analyzed. Results. Although the animals which received prostaglandin analogues experienced transient hypotension, vasopressor was not needed. Two-week animal survival rates were 30%. in the control group, 100%, in the MP group, and 100%,, in the OP group. The treatments with prostaglandin analogues improved HTBF, attenuated liver enzyme release, and lessened histological abnormalities. Conclusion. In conclusion, treatments with misoprostol or OP-41483 successfully prevented liver damage after 2-h warm ischemia. Improvement or liver microcirculation at the early phase of reperfusion played an important role in liver protection by these prostaglandin analogues.