The manganese superoxide dismutase mimetic, M40403, protects adult mice from lethal total body irradiation.

Abstract

Over-expression of manganese superoxide dismutase (MnSOD) protects tissues from radiation. M40403 is a stable non-peptidyl mimetic of MnSOD that crosses cell membranes and is effective in reducing experimental inflammation. Male BALB/c mice were injected intraperitoneally (i.p.) and subcutaneously (s.c.) with M40403, 30 min before 6.5, 7.5 and 8.5 Gy total body irradiation (TBI). Whereas all control injected mice died after receiving 8.5 Gy TBI by day 17, 30 day survival of mice pre-treated i.p. with 40, 30, 20 or 10 mg/kg was 100%, 90%, 81% and 25%, respectively. The Dose Reduction Factor 50/30 for animals treated with 30 mg M40403 s.c. 30 min prior to TBI was 1.41. Decreased apoptosis of the large and particularly the small bowel and marked recovery of both lymphoid and hematopoietic tissues occurred in the M40403 pre-treated animals. M40403 is effective in reducing TBI-induced tissue destruction and has potential as a new radioprotective agent.

• Authors: John S Thompson, Yanxia Chu, Judith Glass, Andrea A Tapp, Stephen A Brown
• Journal: Free radical research (Free Radic Res) Vol. 44 Issue 5 Pg. 529-40 (May 2010) ISSN: 1029-2470 [Electronic] England
• PMID: 20298121 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antioxidants
• Organometallic Compounds
• Radiation-Protective Agents
• imisopasem manganese
• Manganese
• Superoxide Dismutase

Topics

• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects, radiation effects)
• Biomimetic Materials (pharmacology)
• Dose-Response Relationship, Radiation
• Hematopoietic System (drug effects, pathology, radiation effects)
• Lymphoid Tissue (drug effects, pathology, radiation effects)
• Male
• Manganese
• Mice
• Mice, Inbred BALB C
• Organometallic Compounds (chemistry, pharmacology)
• Oxidative Stress (drug effects, radiation effects)
• Radiation-Protective Agents (chemistry, pharmacology)
• Superoxide Dismutase
• Survival Rate
• Whole-Body Irradiation