Anti-oxidant activity mediated neuroprotective potential of trimetazidine on focal cerebral ischaemia-reperfusion injury in rats.
1. The present study was designed to investigate the neuroprotective effect of trimetazidine (TMZ) following focal cerebral ischaemia-reperfusion (I/R) injury in rat forebrain. 2. Cerebral I/R injury was induced in rats by middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion for 22 h. Trimetazidine (5 and 25 mg/kg, i.p.) was administered 1 h after induction of MCAO. The effects of TMZ were investigated by measuring neurological deficit, volume of infarct and brain swelling after 22 h reperfusion. Oxidative stress and inflammatory reactivity were assessed by estimating anti-oxidant markers and myeloperoxidase (MPO) activity in brain homogenates. Rectal temperature was measured during the study. The effects of TMZ on blood-brain barrier (BBB) permeability and apoptosis were also investigated in rat brain. Apoptosis was observed by DNA fragmentation studies using agarose gel electrophoresis. 3. Treatment with TMZ significantly (P < 0.01) reduced infarct volume and brain swelling. Superoxide dismutase (SOD) activity was reduced in ipsilateral hemispheres of vehicle (saline)-treated reperfused (RI) animals. Treatment with TMZ significantly restored SOD activity (P < 0.01) and glutathione levels (P < 0.05) after reperfusion compared with RI animals. Lipid peroxidation, MPO activity, BBB permeability and rectal temperature were all significantly (P < 0.01, P < 0.05 and P < 0.001, respectively) reduced in TMZ-treated animals compared with RI animals. 4. These results suggest that TMZ protects the brain against cerebral I/R injury and that this neuroprotective activity could be mediated by its anti-oxidant properties. The reduction in rectal temperature by TMZ treatment may be responsible for maintaining the delicate energy balance during I/R injury in rat brain and could have contributed to the neuroprotective activity of TMZ.
Dhote
Vipin
V
Pharmacy Department, The MS University of Baroda, Faculty of Technology and Engineering, Kalabhavan, Baroda, Gujarat, India.
Balaraman
Ramachandran
R
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers; D001812:Blood-Brain Barrier / Q000187:drug effects; D001831:Body Temperature; D001921:Brain / Q000201:enzymology / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy; D002545:Brain Ischemia / Q000473:pathology*; D002544:Cerebral Infarction / Q000188:drug therapy; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000502:physiology; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D014292:Trimetazidine / Q000627:therapeutic use*
D000975:Antioxidants; D015415:Biomarkers; D018696:Neuroprotective Agents; D009195:Peroxidase; D014292:Trimetazidine