The manganese superoxide dismutase mimetic, M40403, protects adult mice from lethal total body irradiation
- 1 January 2010
- journal article
- Published by Taylor & Francis Ltd in Free Radical Research
- Vol. 44 (5), 529-540
- https://doi.org/10.3109/10715761003649578
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.Keywords
This publication has 29 references indexed in Scilit:
- Specificity Protein 1-dependent p53-mediated Suppression of Human Manganese Superoxide Dismutase Gene ExpressionOnline Journal of Public Health Informatics, 2006
- Delayed Radioprotection by NFκB-Mediated Induction of Sod2 (MnSOD) in SA-NH Tumor Cells after Exposure to Clinically Used Thiol-Containing DrugsRadiation Research, 2004
- Antioxidant Enzymes and ApoptosisDrug Metabolism Reviews, 2004
- Preclinical studies on the radioprotective efficacy and pharmacokinetics of subcutaneously administered amifostineSeminars in Oncology, 2002
- Superoxide Dismutase MimeticsPulmonary Pharmacology & Therapeutics, 2002
- Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischaemia and reperfusion injury in vivoBritish Journal of Pharmacology, 2002
- Activation of NFκB and MnSOD gene expression by free radical scavengers in human microvascular endothelial cellsFree Radical Biology & Medicine, 2001
- Manganese superoxide dismutase in diseaseFree Radical Research, 2001
- A Nonpeptidyl Mimic of Superoxide Dismutase with Therapeutic Activity in RatsScience, 1999
- Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice.Proceedings of the National Academy of Sciences of the United States of America, 1996