MK-801 POTENTIATES THE GLUTATHIONE DEPLETION INDUCED BY ACETAMINOPHENIN RAT-BRAIN

To investigate the relationship between acetaminophen (APA) and calciu m ion (Ca2+) homeostasis within the glutathione (GSH) oxidation-reduct ion cycle, male rats were given APA (one buccal injection of 3 g/kg) a nd/or MK-801 (three intraperitoneal injections each of 0.2 mg/kg), a n oncompetitive N-methyl-D-aspartate receptor antagonist. There were inj ection-vehicle control groups for all active drug groups; an additiona l control group received no injections (total of seven experimental gr oups; 134 rats). The brain tissue was examined 8 hours after administr ation of the drugs to determine the levels of GSH, APA, and protein. A PA produced a 25% decrease in GSH that was strongly enhanced by the co administration of MK-801 (49% decrease). MK-801 alone produced a 32% d ecrease in brain levels of GSH. This reduction of GSH is probably link ed to the interference of Ca2+ homeostasis and can be considered as a trigger for cell injury in oxidative stress.