Neuroprotection against hypoxia-ischemia in neonatal rat brain by novel superoxide dismutase mimetics.
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.
Shimizu
Katsuyoshi
K
Departments of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA. katsuyoshis@aol.com
Rajapakse
Nishadi
N
Horiguchi
Takashi
T
Payne
R Mark
RM
Busija
David W
DW
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008345:Manganese; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000627:therapeutic use*
C426066:M40401; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; C121876:imisopasem manganese; D008345:Manganese; D013482:Superoxide Dismutase