Methylene blue protects intestinal mucosa from free radical-mediated sublethal radiation damage

Susceptibility of the intestine to radiation damage is a primary reason for the failure of external beam radiation to cure intra-abdominal cancer. High-dose irradiation causes intestinal denudation, fluid loss, and resultant shock. Simple and effective methods for protecting the intestine from irradiation damage are not available. Many biological effects of ionizing irradiation are caused by free radical intermediates. We have previously reported that many of the toxicities of doxorubicin, a classic free radical generating anticancer agent, are blocked by methylene blue pretreatment. We have now found that pretreatment with methylene blue protects rats from intestinal damage, as measured histologically and by quantitative stool blood determinations. Whereas the exact mechanisms of this protection remain elusive, we believe this method of modulating the therapeutic index of ionizing radiation deserves additional preclinical and clinical study.