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

• Published in: The European journal of surgery Vol. 165; no. 4; pp. 369 - 377
• Main Authors: Tümer, Ali Riza, Kama, Nuri Aydın, Tümer, Leyla, Reis, Erhan, Müftüoğlu, Sevda
• Format: Journal Article
• Language: English
• Published: UK Taylor & Francis, Ltd 01-04-1999; Taylor & Francis
• Subjects: Anastomosis, Surgical; Animals; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - pharmacology; Antineoplastic agents; Biological and medical sciences; Colon - surgery; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Fluorouracil - administration & dosage; Fluorouracil - pharmacology; Injections, Intraperitoneal; Medical sciences; Microscopy, Electron; Pharmacology. Drug treatments; Rabbits; Stomach, duodenum, intestine, rectum, anus; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Wound Healing - drug effects; Zinc - administration & dosage; Zinc - pharmacology; Antineoplastic agent; Animal model; Adjuvant treatment; Rabbit; Intestinal disease; Evolution; Colon; Experimental surgery; Cicatrization; Fluorouracil; Enzyme; Transferases; Fluoropyrimidine derivatives; Surgical anastomosis; Enzyme inhibitor; Malignant tumor; Lagomorpha; Thymidylate synthase; Zinc; Colonic disease; Trace element; Vertebrata; Mammalia; Treatment; Methyltransferases; Antimetabolic; Animal; Digestive diseases; Pyrimidine derivatives
• ISSN: 1102-4151; 1741-9271
• DOI: 10.1080/110241599750006929

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. Copyright © 1999 Taylor and Francis Ltd.