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.