ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract : Riluzole is used clinically in patients with amyotrophiclateral sclerosis. As oxidative stress, in addition to excitotoxicity, may bea major mechanism of motoneuron degeneration in patients with amyotrophiclateral sclerosis, we examined whether riluzole protects againstnonexcitotoxic oxidative injury. Probably reflecting its weak antiexcitotoxiceffects, riluzole (1-30 μM) attenuated submaximal neuronal deathinduced by 24-h exposure to 30 μM kainate or NMDA, but not that by100 μM NMDA, in cortical cultures. Riluzole also attenuatednonexcitotoxic oxidative injury induced by exposure to FeCl3 in thepresence of MK-801 and CNQX. Consistent with its antioxidative effects,riluzole reduced Fe3+-induced lipid peroxidation, and inhibitedcytosolic phospholipase A2. By contrast, riluzole did not attenuateneuronal apoptosis induced by staurosporine. Rather unexpectedly, 24-48-hexposure to 100-300 μM riluzole induced neuronal death accompaniedby nuclear and DNA fragmentations, which was attenuated by caspase inhibitorcarbobenzyloxy-Val-Ala-Asp-fluoromethyl ketone but not by protein synthesisinhibitor cycloheximide. The present study demonstrates that riluzole hasdirect antioxidative actions, perhaps in part by inhibiting phospholipaseA2. However, in the same neurons, riluzole paradoxically induces neuronal apoptosis in a caspase-sensitive manner. Considering current clinical use of riluzole, further studies are warranted to investigate its potential cytolethal effects.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1999.0720716.x
Permalink
