THE ROLES OF NUTRITIONAL DEPLETION AND DRUG CONCENTRATION IN 5-FLUOROURACIL-INDUCED INHIBITION OF COLONIC HEALING

This study was performed to investigate whether poor nutrition is resp onsible for 5-fluorouracil (5-FU)induced inhibition of large bower hea ling and if the concentration of intraperitoneal tip) 5-FU affects ana stomotic healing. Male Wistar rats underwent a left colonic 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 start ed immediately after surgery and continued until sacrifice after 7 day s. Although the weight loss in the nutritional depletion group exceede d that in the 5-FU group, the anastomotic and skin breaking strength w as lower in the latter group compared with that in the former group (P < 0.01 and P < 0.05, respectively). There were no significant differe nces 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 h igh-concentration group (n = 10, (5 mg/ml ip 5-FU) or a 5-FU low-conce ntration 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 w as reduced to a similar extent in the 5-FU groups (P < 0.01). These re sults indicate that the impaired anastomotic healing after ip 5-FU is not mainly due to nutritional factors or drug concentration. (C) 1994 Academic Press, Inc.