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 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 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 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.
Graf
W
W
Department of Surgery, Akademiska sjukhuset, Uppsala, Sweden.
Weiber
S
S
Jiborn
H
H
Påhlman
L
L
Glimelius
B
B
Zederfeldt
B
B
D000714:Anastomosis, Surgical; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001834:Body Water / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000502:physiology / Q000601:surgery*; D004032:Diet; D005472:Fluorouracil / Q000633:toxicity*; D006909:Hydroxyproline / Q000032:analysis; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014945:Wound Healing / Q000187:drug effects*
D006909:Hydroxyproline; D005472:Fluorouracil