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 hippocampus in order to evaluate their changes during ischemia and reperfusion following ischemia. The depletion of GSH was observed during ischemia with a further depletion during post-ischemic reperfusion (P < 0.001), while a significant increase in SOD activity and MDA levels was found only after reperfusion following ischemia (P < 0.001). Animals in which ischemia was followed by reperfusion were treated with a non-competitive NMDA receptor antagonist, MK-801 (1 mg/kg, i.v.), and a radical scavenger, U-83836E (5 mg/kg, i.v.), prior to ischemia. Although a full recovery of GSH levels was not observed following MK-801 and U-83836E pretreatment as compared to control (P < 0.05), MK-801 was more potent than U-83836E in the partial protection of the GSH pool (P < 0.05 and P < 0.01, respectively). The rise in SOD activity and MDA level 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 concentrations evoked by ischemia and reperfusion were partially prevented by the effects of both drugs, MK-801 having the greater effect. This suggests that the NMDA receptor activation may play a role in the generation of reactive oxygen species. On the other hand, the inhibition of lipid peroxidation brought about by both MK-801 or U-83836E suggests the therapeutic efficiency of these agents in ischemia/reperfusion injury.
Durmaz
R
R
Department of Neurosurgery, Medical Faculty of Osmangazi University, Eskisehir, Turkey. rdurmaz@ogu.edu.tr.
Inal
M
M
Angin
K
K
Atasoy
M A
MA
Altinişik
M
M
Tel
E
E
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D002839:Chromans; D018696:Neuroprotective Agents; D010879:Piperazines; C066382:U 78517F; D008315:Malondialdehyde; D016291:Dizocilpine Maleate; D013482:Superoxide Dismutase; D005978:Glutathione