The Roles of Nutritional Depletion and Drug Concentration in 5-Fluorouracil-Induced Inhibition of Colonic Healing

Abstract

This study was performed to investigate whether poor nutrition is responsible for 5-fluorouracil (5-FU)induced inhibition of large bowel healing and if the concentration of intraperitoneal (ip) 5-FU affects anastomotic healing. Male Wistar rats underwent a left coIonic resection and were randomly assigned to a control group (n = 9, ip NaCl, normal diet), a nutritional depletion group (n = 12, ip NaCl, restricted diet), or a 5-FU group (n = 12, ip 5-FU, normal diet). Treatment was started immediately after surgery and continued until sacrifice after 7 days. Although the weight loss in the nutritional depletion group exceeded that in the 5-FU group, the anastomotic and skin breaking strength was lower in the latter group compared with that in the former group (P < 0.01 and P < 0.05, respectively). There were no significant differences in breaking strength between the nutritional depletion group and controls. A second series of male Wistar rats were similarly operated on and randomly assigned to a control group (n = 6, ip NaCl), a 5-FU high-concentration group (n = 10, (5 mg/ml ip 5-FU) or a 5-FU low-concentration group (n = 10, (1 mg/ml ip 5-FU). The 5-FU dose was the same in the two latter groups. The anastomotic breaking strength on Day 7 was reduced to a similar extent in the 5-FU groups (P < 0.01). These results indicate that the impaired anastomotic healing after ip 5-FU is not mainly due to nutritional factors or drug concentration.