The N-Methyl-d-Aspartate Receptor Antagonist MK-801 Prevents Thallium-Induced Behavioral and Biochemical Alterations in the Rat Brain.
Thallium (Tl(+)) is a toxic heavy metal capable of increasing oxidative damage and disrupting antioxidant defense systems. Thallium invades the brain cells through potassium channels, increasing neuronal excitability, although until now the possible role of glutamatergic transmission in this event has not been investigated. Here, we explored the possible involvement of a glutamatergic component in the Tl(+)-induced toxicity through the N-methyl-d-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) in rats. The effects of MK-801 (1 mg/kg, intraperitoneally [ip]) on early (24 hours) motor alterations, lipid peroxidation, reduced glutathione (GSH) levels, and GSH peroxidase activity induced by Tl(+) acetate (32 mg/kg, ip) were evaluated in adult rats. MK-801 attenuated the Tl(+)-induced hyperactivity and lipid peroxidation in the rat striatum, hippocampus and midbrain, and produced mild effects on other end points. Our findings suggest that glutamatergic transmission via NMDA receptors might be involved in the Tl(+)-induced altered regional brain redox activity and motor performance in rats.
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico Doctorado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico Laboratorio de Bioenergética y Envejecimiento Celular, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico.
Laura
L
Osorio-Rico
Laboratorio de Patología Experimental, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
Juana
J
Villeda-Hernández
Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
Abel
A
Santamaría
Laboratorio de Bioenergética y Envejecimiento Celular, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico.
Mina
M
Königsberg
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico absada@yahoo.com mkf@xanum.uam.mx sonia_galvan@yahoo.com.
Sonia
S
Galván-Arzate
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects; D013793:Thallium / Q000633:toxicity*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D013793:Thallium; D005979:Glutathione Peroxidase; D005978:Glutathione
brain regions; glutamate receptors; heavy metals toxicity; neuroprotection; oxidative stress