Radioprotection of the rat intestinal mucosa by tirilazad.

PURPOSE

To assess intestinal radioprotection by systemic or lumenal tirilazad mesylate and to test potential tumour radioprotection.

MATERIALS AND METHODS

Segments of the mid small bowel were surgically exteriorized. Tirilazad was given either intravenously or intralumenally 30 min prior to 11 Gy of X-irradiation to the exteriorized intestine. Tissues were harvested 5 days later to measure crypts per circumference and mucosal height. Potential tumour protection was assessed in a mouse sarcoma model. Tumours implanted in the hind limb were allowed to grow until a standard volume was attained, then irradiated (10 Gy) 30 min after intravenous (i.v.) administration of saline or tirilazad. Tumour growth was recorded for the next 22 days to determine if pretreatment with tirilazad interfered with radiation effects.

RESULTS

Systemic tirilazad provided no protection against intestinal damage and did not alter tumour growth after irradiation. Topical tirilazad yielded highly significant protection of intestinal mucosa.

CONCLUSIONS

These preliminary observations showed that topical tirilazad diminished radiation enteritis. Systemic drug had no effect on the severity of damage to the intestine nor did it inhibit radiation effects on a tumour.