U-83836E prevents kainic acid-induced neuronal damage

Camins, A; Gabriel, C; Aguirre, L; Sureda, FX; Pubill, D; Pallas, M; Escubedo, E; Camarasa, J


The effect of kainic acid (KA) on mitochondrial membrane potential (MMP) and reactive-oxygen species (ROS) production was studied in dissociated cerebellar granule cells from rat pups. KA induced a maximum increase of 361%+/-35% in ROS production. The lazaroid compound U-83836E (at concentrations ranging from 10(-9) to 5x10(-6) M) completely inhibited this increase, with an IC50 value of 3.02+/-1.08x10(-7) M. KA also decreased the mitochondrial membrane potential (MMP), with a maximum decrease of about 30%. Absence of Na+ in the incubation medium did not significantly alter the effect of KA on MMP. As expected, the AMPA/kainate receptor antagonist NBQX inhibited the effects of KA on MMP with an IC50 value of 1.1+/-0.8 mu M. However, the lazaroid U-83836E, indomethacin, nor-dihydroguaiaretic acid and L-nitroarginine all failed to inhibit the KA-induced decrease in the MMP. Finally, to assess the neuroprotective effect of U-83836E on KA-induced neurotoxicity in vivo, the increase in the peripheral-type benzodiazepine receptor density in rat hippocampus was measured. Treatment with KA increased the B-max to 1341+/-192 fmol mg(-1). When U-83836E was coadministered with KA, the B-max was reduced to 765+/-122 fmol mg(-1), which was not significantly different from the B-max obtained from untreated rats (B-max 518+/-33 fmol mg(-1)). We conclude that treatment with the lazaroid U-83836E might be a suitable therapeutic strategy in neurodegenerative disorders.

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Título según WOS: ID WOS:000073661700009 Not found in local WOS DB
Volumen: 357
Número: 4
Editorial: Springer
Fecha de publicación: 1998
Página de inicio: 413
Página final: 418


Notas: ISI