Neuroprotection against hypoxia-ischemia in neonatal rat brain by novel superoxide dismutase mimetics.

Abstract

We investigated the effects of two new low molecular weight nonpeptidyl superoxide dismutase (SOD) mimetics (M40403/M40401; MetaPhore Pharmaceuticals) on infarct volume after hypoxia-ischemia injury (H/I) in immature rats. Animals received vehicle or different doses of M40403 or M40401 i.p. 2 h before exposure to 3 h of 8% hypoxia. The infarct volume of the hemisphere ipsilateral to carotid ligation 24 h later was 73.9+/-8.9% in vehicle animals (n=9), and decreased to 39.7+/-7.2% (P<0.05, n=10) in animals treated with 3 mg/kg M40403 and to 37.2+/-6.4% for animals receiving 3 mg/kg M40401 (P<0.05, n=8). These data indicate that the SOD mimetics M40403 and M40401 have protective effects against hypoxic-ischemic brain injury, and suggest the involvement of superoxide anion in neuronal cell injury during H/I.

• Authors: Katsuyoshi Shimizu, Nishadi Rajapakse, Takashi Horiguchi, R Mark Payne, David W Busija
• Journal: Neuroscience letters (Neurosci Lett) Vol. 346 Issue 1-2 Pg. 41-4 (Jul 31 2003) ISSN: 0304-3940 [Print] Ireland
• PMID: 12850543 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• M40401
• Neuroprotective Agents
• Organometallic Compounds
• imisopasem manganese
• Manganese
• Superoxide Dismutase

Topics

• Animals
• Animals, Newborn
• Brain (drug effects, enzymology, pathology)
• Hypoxia-Ischemia, Brain (drug therapy, enzymology, pathology)
• Manganese
• Neuroprotective Agents (pharmacology, therapeutic use)
• Organometallic Compounds (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Superoxide Dismutase (pharmacology, therapeutic use)