Neuroprotective effect of dapsone against quinolinate- and kainate-induced striatal neurotoxicities in rats.
We tested the ability of dapsone, a well-known antibiotic and antiinflammatory drug, to attenuate both the quinolinic acid (an NMDA agonist of glutamate receptors)- and kainic acid (a non-NMDA agonist of glutamate receptors)-induced in vivo neurotoxicities in rats. Circling behaviour and striatal gamma-aminobutyric acid (GABA) depletion were considered as behavioural and neurochemical end-points of brain toxicity. Rotation behaviour, evaluated six days after the intrastriatal injection of quinolinic acid (130 +/- 19 ipsilateral turns/hr), was attenuated by doses of 12.5 mg/kg and 25 mg/kg of dapsone (50 +/- 9 and 63 +/- 9 turns/hr, respectively). Striatal GABA levels (237.3 +/- 15.1 micrograms/g in control rats), found depleted at day 7 after quinolinic acid (98.3 +/- 8.6 micrograms/g), were also protected by dapsone at doses of 12.5 and 25 mg/kg (167.7 +/- 19.5 and 236.4 +/- 46.6 micrograms/g, respectively). No protective effects were observed on quinolinic acid-induced neurotoxicity, as evaluated by both parameters, at lower doses of dapsone (6.25 and 9.375 mg/kg). The action of dapsone, at the dose of 12.5 mg/kg, was also measured on kainic acid-induced depletion of the striatal GABA levels. Animals treated with dapsone + kainic acid (182.8 +/- 27.1 micrograms/g) showed significant attenuation of GABA depletion, as compared to rats treated with kainic acid alone (122.2 +/- 19.9 micrograms/g). These findings provide evidences to suggest that dapsone is acting as a neuroprotective agent against excitotoxicity induced by glutamate receptor agonists.
Santamaría
A
A
Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, México D.F., Mexico.
Ordaz-Moreno
J
J
Rubio-Osornio
M
M
Solís-Hernández
F
F
Ríos
C
C
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003622:Dapsone / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D008297:Male; D016202:N-Methylaspartate / Q000819:agonists; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D003622:Dapsone; D017378:Quinolinic Acid; D007608:Kainic Acid