Intraportal prostaglandin E1 ameliorates the toxicity of intraportal 2'-deoxy-5-fluorouridine in rats.

This study was designed to see whether intraportal infusion with prostaglandin E1 (PGE1) could reduce mortality associated with high-dose intraportal infusion of 2'-deoxy-5-fluorouridine (FUDR). Thirty anesthetized male Sprague-Dawley rats underwent laparotomy and placement of osmotic pumps (Alzet 2ML1) infusing a branch of the portal vein. Animals were weighed and infused for 1 week with buffer (control), FUDR (3 mg/kg/day), or FUDR (3 mg/kg/day) + PGE1 (0.1 microgram/kg/min). Blood was then obtained for liver functions and white blood cell count. The body and liver were weighed. No animals died in the control group. Five animals in the FUDR group died during the fourth (n = 1), sixth (n = 2), and seventh (n = 2) days of infusion. Only one animal in FUDR + PGE1 group died during the sixth day of infusion. Weight loss was greater in both treated groups than in controls. Animals receiving PGE1 lost significantly less weight than animals receiving FUDR alone. These data suggest that intraportal PGE1 ameliorates the hepatic toxicity of intraportal FUDR. The effect of PGE1 on the tumoricidal properties of FUDR infused by either the portal vein or the hepatic artery remains to be studied.