Dapsone prevents morphological lesions and lipid peroxidation induced by quinolinic acid in rat corpus striatum.
Increasing doses of dapsone were tested on rats administered intrastriatally with quinolinic acid in order to evaluate a possible protective action of this drug on the striatal lesions produced after the excessive activation of N-methyl-D-aspartate receptors. Morphological lesions were evaluated 7 days after the intrastriatal injection of quinolinate (240 nmol/microl) by light microscopy, and the ratio of neuronal damage per field was also estimated as a quantitative index of the striatal toxicity. Quinolinate alone produced extensive necrosis and loss of striatal neurons. No protective effects on the striatal tissue from quinolinate-treated rats were observed at lower doses of dapsone (6.25 and 9.375 mg/kg). However, at higher doses (12.5 and 25 mg/kg), dapsone prevented significantly the striatum from quinolinate toxicity. Dapsone alone had no effect on the striatal tissue from control rats. A single dose of dapsone (12.5 mg/kg) was tested also on the index of lipid peroxidation 2 h after the striatal injection of quinolinate, resulting in a significant protection (78% vs. QUIN). Findings of this study, in accordance with our previous reports, demonstrate the ability of dapsone to prevent the neuronal damage associated with the excitatory action of quinolinate via overactivation of NMDA receptors, and provide evidences to support the hypothesis that this drug is acting against the pattern of toxicity elicited by agonists of glutamate receptors.
Rodríguez
E
E
Laboratory of Excitatory Aminoacids, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico DF, Mexico.
Méndez-Armenta
M
M
Villeda-Hernández
J
J
Galván-Arzate
S
S
Barroso-Moguel
R
R
Rodríguez
F
F
Ríos
C
C
Santamaría
A
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D003622:Dapsone / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000975:Antioxidants; D016194:Receptors, N-Methyl-D-Aspartate; D003622:Dapsone; D017378:Quinolinic Acid