The effects of MK-801 and U-83836E on post-ischemic reperfusion injury in rat brain

Rats were subjected to incomplete cerebral ischemia induced by occlusion of common carotid arteries for 30 min, and subsequent reperfusion for 15 min. The concentrations of reduced glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) activity were determined in the dorsal hippocam pus in order to evaluate their changes during ischemia and reperfusion foll owing ischemia. The depletion of GSH was observed during ischemia with a fu rther depletion during post-ischemic reperfusion (P<0.001), while a signifi cant increase in SOD activity and MDA levels was found only after reperfusi on following ischemia (P<0.001). Animals in which ischemia was followed by reperfusion were treated with a non-competitive NMDA receptor antagonist, M K-801 (1 mg/kg, i.v.), and a radical scavenger, U-83836E (5mg/kg, i.v.), pr ior to ischemia. Although a full recovery of GSH levels was not observed fo llowing MK-801 and U-83836E pretreatment as compared to control (P<0.05), M K-801 was more potent than U-83836E in the partial protection of the GSH po ol (P<0.05 and P<0.01, respectively). The rise in SOD activity and MDA leve l were brought close to those of control due to the effects of both MK-801 and U-83836E (P>0.05). In conclusion, the tissue changes in GSH concentrati ons evoked by ischemia and reperfusion were partially prevented by the effe cts of both drugs, MK-801 having the grater effect. This suggests that the NMDA receptor activation may play a role in the generation of reactive oxyg en species. On the other hand, the inhibition of lipid peroxidation brought about by both MK-801 or U-83836E suggests the therapeutic efficiency of th ese agents in ischemia/reperfusion injury.