Excessive generation of
free radicals and decreased levels of the
antioxidant enzymes such as
superoxide dismutase (SOD) and
catalase have been observed after brain ischemic
reperfusion injury. In the present study, we have investigated the neuroprotective potential of
MnTMPyP (Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride), a SOD/
Catalase mimetic in bilateral carotid artery occlusion model of global
cerebral ischemia in Mongolian gerbils. Five minutes of bilateral carotid artery occlusion produced global
cerebral ischemia, which was evident from the neurological deficits, spontaneous motor activity and the decrease in the number of viable hippocampal CA1 neurons. Global
ischemia was also associated with increased levels of
malondialdehyde, decreased levels of SOD and
catalase, and increased TUNEL (
terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) positive cells, indicating oxidative stress and DNA fragmentation. Administration of a single dose of
MnTMPyP, 1 mg/kg i.p. (30 min before occlusion), produced no significant neuroprotection; however, 3 mg/kg i.p. (30 min before to occlusion) produced significant reduction in neurological score, spontaneous motor activity and CA1 pyramidal neuronal damage.
MnTMPyP also attenuated the increased levels of
malondialdehyde and improved the levels of SOD and
catalase, and inhibited DNA fragmentation in the ischemic animals. Multiple administration of
MnTMPyP, 3 mg/kg i.p. (three times: 30 min before, 1 h and 3 h after occlusion), produced better neuroprotection as compared to single dose administration. This study demonstrates that the
neuroprotective effect of
MnTMPyP in global
ischemia is mediated through reduction in oxidative stress and DNA fragmentation.