Screening of medicines to alleviate intestine damage by high dose radiation: Effect of regulators for the autonomic nervous system.

Abstract

  Intestine is severely damaged by local and systemic exposure of high dose (above 10Gy) of ionizing radiation. To find the therapeutic methodology, we examined drugs which contribute to healing of the lethal intestinal damage following radiation using the experimental animal model.
  Since it was difficult to find the regions of lethal damage in the long intestine, survival rate was used as an indicator. Damaging of whole intestine was produced by abdominal exposure of 16.5 or 18.5 Gy of x-ray to anesthetized C3H/He mice. Parenteral nutrition and drugs were concomitantly injected to the mice from Day-1 to 10 after the irradiation. Even though the nutrition was introduced to the mice, the body-weight was decreased till Day-7. Although mice with increase in the weight at Day-8 were survived at least Day-28, others were died within 10 days.
  Co-administration of nutrition with sympatholytic drugs, parasympathomimetic agents or benzodiazepine derivatives decreased the survival rate. In contrast, co-injection with alpha-adrenergic receptor stimulators, parasympatholytic agents and antispasmodics shortened the period of the decrease in the body-weight and increased survival rate. This suggests that the repair of intestine following radiation is suppressed by the relaxation of the smooth muscle of intestine.