Acceleration of regeneration by anabolic steroid in mucous membrane of small intestine damaged by high-dose radiation.

Abstract

Mucous membrane of small intestine is radiation-sensitive and damaged severely by local or systemic exposure of high dose of ionizing radiation via apoptosis in the crypt or the vascular endothelial cells. To find the therapeutic methodology, we examined drugs which contribute to regeneration of mucous membrane following lethal intestinal damage by radiation in mouse.
Damaging of whole small intestine was induced by abdominal exposure of 15.7 Gy of x-ray to anesthetized C3H/He mice. Parenteral nutrition and drugs to be examined were concomitantly injected to the mice from Day-1 to 10 after the irradiation. Damages by x-ray and effects of drugs were determined by the survival rates as well as histochemical analysis and quantification of mRNA in mucous membrane of small intestine. Mucous tissue with BrdU-incorporated cells were compensated from Day-5 to 8. Before the regeneration was evidently observed at Day-4, c-myb mRNA level was promptly increased. Mice in which the most of mucous tissue was covered with the regenerated tissue at Day-8 increased its body weight and survived until Day-28. Survival rate of approximately 60% were observed without introduction of drugs.
Among various frequently-used drugs, post-irradiational introduction of anabolic steroid, 19-nortestosterone is significantly effective in improvement of the survival rate. Both the level of c-myb mRNA at Day-4 and the area of compensated tissue at Day-5 were increased in mucous membrane. While estrogen decreased these parameters, the results show that the androgenic hormone accelerates regeneration of mucous membrane damaged by radiation in the small intestine.