Neuroprotective effect of combination of poly (ADP-ribose) polymerase inhibitor and antioxidant in middle cerebral artery occlusion induced focal ischemia in rats.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Punjab, India We have investigated the neuroprotective potential of combination of poly (ADP-ribose) polymerase inhibitor (nicotinamide or 3-aminobenzamide) and antioxidant (melatonin) in middle cerebral artery occlusion (MCAo) induced focal ischemia in rats. MCAo of 2 h followed by 22 h reperfusion produced large volume of cerebral infarction (mean +/- SEM 211.38 +/- 8.35 mm3), volume of edema (60 +/- 2 mm3) and neurological deficits (4.45 +/- 0.25). Combination of nicotinamide (500 mg kg(-1), i.p.) and melatonin (10 mg kg(-1), i.p.) significantly decreased infarct volume to 48 +/- 2.58 mm3 as compared to their individual drug (nicotinamide 76 +/- 12.49mm3, melatonin 76.17 +/- 1.24 mm3). A significant improvement was observed in edema volume and neurological deficits with this combination. Combination of 3-aminobenzamide (20 mg kg(-1), i.p.) and melatonin (10 mg kg(-1), i.p.) also produced similar reduction in infarction, edema and neurological score. These results indicate that the combination of poly (ADP-ribose) polymerase inhibitor and antioxidant produce enhanced neuroprotection. Clinical availability and wide therapeutic margin of nicotinamide and melatonin make them a promising drug combination for clinical evaluation in stroke patients.