Efficacy of radioprotective agents in preventing small and large bowel radiation injury.
OBJECTIVE
A variety of adjuvant treatments and cytoprotective agents have been proposed to lessen the toxicity of radiation therapy. The following study was designed to evaluate the benefit of six agents or combinations using anastomotic bursting strength as a measure of transmural radiation injury.


METHODS
The 40-Gy study consisted of the following. Seventy-two male Sprague-Dawley rats were divided into eight equal groups: nonradiated control, radiated untreated control, and six radiated treated groups. The radioprotective treatments included ribose-cysteine (Rib-Cys), WR-2721, glutamine, vitamin E, MgCl2/adenosine triphosphate, and RibCys/glutamine in combination. Radiated animals received 40 Gy to the abdomen. Two weeks after radiation, all animals underwent small bowel and colonic resection with primary anastomosis. Animals were sacrificed one week postoperatively, at which time anastomoses were evaluated and bursting strengths determined. The 70-Gy study consisted of the following. The same protocol was repeated for five groups of nine rats divided into nonradiated, radiated untreated, and three radiated treated groups receiving RibCys (8 mmol/kg), RibCys (20 mmol/kg), and WR-2721. All radiated animals received 70-Gy doses.


RESULTS
In the 40-Gy group, there were 10 radiation-related deaths and 6 anastomotic leaks among 70 rats studied. None of the differences between groups were significant. Nonradiated control group small bowel and large bowel anastomotic bursting pressures were significantly elevated compared with all radiated groups. Compared with radiated controls, there were significant improvements in small bowel bursting strength in the RibCys, WR-2721, RibCys-glutamine, and vitamin E groups and significant improvement in colonic bursting strength in MgCl2/adenosine triphosphate, WR-2721, and RibCys groups. In the 70-Gy group, all nine nonradiated control rats survived. All eight untreated radiated control rats died, four of eight WR-2721 animals died (P = 0.03), all RibCys (8 mmol/kg) animals died (P = 0.03), and three of nine treated with RibCys (20 mmol/kg) survived (P = 0.08).


CONCLUSIONS
WR-2721 and RibCys gave consistent protection against large and small bowel radiation injury. The lower incidence of treatment-related toxicity and potentially equal or greater radioprotective effects may make RibCys more clinically useful than WR-2721.
Carroll
M P
MP
Department of Surgery, Hennepin County Medical Center, University of Minnesota, Minneapolis 55415, USA.
Zera
R T
RT
Roberts
J C
JC
Schlafmann
S E
SE
Feeney
D A
DA
Johnston
G R
GR
West
M A
MA
Bubrick
M P
MP
D000255:Adenosine Triphosphate / Q000627:therapeutic use; D004999:Amifostine / Q000627:therapeutic use; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives; D004359:Drug Therapy, Combination; D005973:Glutamine / Q000008:administration & dosage / Q000627:therapeutic use; D007420:Intestine, Large / Q000528:radiation effects*; D007421:Intestine, Small / Q000528:radiation effects*; D015636:Magnesium Chloride / Q000627:therapeutic use; D008297:Male; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use; D053778:Thiazolidines; D014810:Vitamin E / Q000627:therapeutic use
D011837:Radiation-Protective Agents; D013844:Thiazoles; D053778:Thiazolidines; D015636:Magnesium Chloride; D005973:Glutamine; D014810:Vitamin E; C070066:2-(1',2',3',4'-tetrahydroxybutyl)thiazolidine-4-carboxylic acid; D000255:Adenosine Triphosphate; D003545:Cysteine; D004999:Amifostine