Therapy of radiation damage to normal tissues with selective inhibitors of cyclooxygenase-2. I. YM177 tends to reduce mouse mortality from the haemopoietic syndrome

Purpose. Non-steroidal anti-inflammatory drugs, i.e, non-selective inhibitors of cyclooxygenase (COX)-1 and - 2, are well known to reduce adverse radiation reactions when given after the exposure. The question remains open as to whether or not newly developed, better-tolerated selective COX-2 inhibitors act likewise. Methods and Materials: A selective COX-2 inhibitor (YM177) was given to whole body X-irradiated mice (5.5-6.5 Gy) starting 24 hr after the exposure until the end of a monthly observation period in doses ranging from 0.17 to 3.4 mg/ kg•day. Results. Administration of ≥0.68 mg YM177/kg•day proved ineffective, whereas two lower dose levels of YM177 reduced the overall mortality from 64% to 54% by making radiation dose-mortality curve of common origin considerably shallower. A non-linear correlation analysis using a Logit plot revealed a significant difference in the mortality curves between placebo group and YM177 treatments (p≤0.023 by one-tailed t-test). Conclusions. Prostanoids synthesized by COX-2 can contribute to death from the haemopoietic syndrome. Similar studies on other organ systems are desirable.