Effects of 5-fluorouracil and zinc on healing of colonic anastomoses in rabbits

Eur J Surg. 1999 Apr;165(4):369-77. doi: 10.1080/110241599750006929.

Abstract

Objective: To find out if 5-fluorouracil (5-FU) given intraperitoneally to rabbits impaired the healing of colonic anastomoses, and whether giving zinc might reverse the effect.

Design: Laboratory study.

Setting: Teaching hospital, Turkey.

Animals: 32 New Zealand white rabbits.

Interventions: All animals had 1cm of large bowel resected 10cm proximal to the peritoneal reflection and continuity restored by end-to-end anastomosis. They were divided into four groups and given intraperitoneal injections of saline (control group), 5-FU 10mg/kg/day in a concentration of 5mg/ml saline (5-FU alone group), zinc 2mg/kg/day (zinc alone group), and the same doses of 5-FU and zinc (5-FU + zinc group). The injections were given immediately after operation and daily for 4 days. The rabbits were killed at 7 days.

Main outcome measures: Bursting pressures, tissue hydroxyproline concentrations, tissue zinc concentrations, and light and electron microscopic appearances.

Results: Six rabbits died of the complications of anaesthesia and 4 of sepsis leaving 7, 6, 7, and 6 rats in the four groups respectively. Mean (SD) anastomotic bursting pressures were significantly reduced in the 5-FU group compared with controls (5 (2) compared with 7 (1) mm Hg, p: 0.05) and collagen synthesis (indicated by reduced tissue hydroxyproline concentrations) was also decreased (7.1 (0.9) compared with 9.1 (1.5), p < 0.05). Rabbits given 5-FU + zinc had significantly higher bursting pressures than those given 5-FU alone (9 (2) compared with 5 (2), p: 0.01). Bursting pressures were also significantly higher in those given zinc alone, but hydroxyproline concentrations were similar to those in the control group. Histological examination showed that 5-FU alone significantly impaired the healing process, and those in the 5-FU + zinc group healed better than those in the 5-FU alone group.

Conclusions: 5-FU given intraperitoneally significantly impaired the healing of colonic anastomoses in rabbits, and zinc reversed this effect.

MeSH terms

  • Anastomosis, Surgical
  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / pharmacology*
  • Colon / surgery*
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacology*
  • Injections, Intraperitoneal
  • Microscopy, Electron
  • Rabbits
  • Wound Healing / drug effects*
  • Zinc / administration & dosage
  • Zinc / pharmacology*

Substances

  • Antimetabolites, Antineoplastic
  • Zinc
  • Fluorouracil