The protective effect of M40401, a superoxide dismutase mimetic, on post-ischemic brain damage in Mongolian gerbils.
BACKGROUND
Overproduction of free radical species has been shown to occur in brain tissues after ischemia-reperfusion injury. However, most of free radical scavengers known to antagonize oxidative damage (e.g. superoxide dismutase, catalase), are unable to protect against ischemia-reperfusion brain injury when given in vivo, an effect mainly due to their difficulty to gain access to brain tissues. Here we studied the effect of a low molecular weight superoxide dismutase mimetic (M40401) in brain damage subsequent to ischemia-reperfusion injury in Mongolian gerbils.


RESULTS
In animals undergoing ischemia-reperfusion injury, neuropathological and ultrastructural changes were monitored for 1-7 days either in the presence or in the absence of M40401 after bilateral common carotid artery occlusion (BCCO). Administration of M40401 (1-40 mg/kg, given i.p. 1 h after BCCO) protected against post-ischemic, ultrastructural and neuropathological changes occurring within the hippocampal CA1 area. The protective effect of M40401 was associated with a significant reduction of the levels of malondialdehyde (MDA; a marker of lipid peroxidation) in ischemic brain tissues after ischemia-reperfusion.


CONCLUSIONS
Taken together, these results demonstrate that M40401 provides protective effects when given early after the induction of ischemia-reperfusion of brain tissues and suggest the possible use of such compounds in the treatment of neurological dysfunction subsequent to cerebral flow disturbances.
Mollace
Vincenzo
V
Faculty of Pharmacy, University of Catanzaro Magna Graecia, Roccelletta di Borgia, Catanzaro, Italy. mollace@libero.it
Iannone
Michelangelo
M
Muscoli
Carolina
C
Palma
Ernesto
E
Granato
Teresa
T
Modesti
Andrea
A
Nisticò
Robert
R
Rotiroti
Domenicantonio
D
Salvemini
Daniela
D
D000818:Animals; D002545:Brain Ischemia / Q000150:complications; D004195:Disease Models, Animal; D005849:Gerbillinae; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009942:Organometallic Compounds / Q000627:therapeutic use*; D020011:Protective Agents / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000737:chemistry
C426066:M40401; D009942:Organometallic Compounds; D020011:Protective Agents; D008315:Malondialdehyde; D013482:Superoxide Dismutase