| Riluzole protects from motor deficits and striatal degeneration produced by systemic 3-nitropropionic acid intoxication in rats. | |
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MedLine Citation:
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PMID: 9300407 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The putative neuroprotective effect of riluzole was investigated in a rat model of progressive striatal neurodegeneration induced by prolonged treatment (three weeks, intraperitoneal) with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase. Quantitative analysis of motor behaviour indicated a significant protective effect (60%) of riluzole (8 mg/kg/day) on 3-nitropropionic acid-induced motor deficits as assessed using two independent motor tests. Furthermore, quantitative analysis of 3-nitropropionic acid-induced lesions indicated a significant 84% decrease in the volume of striatal damage produced by 3-nitropropionic acid, the neuroprotective effect apparently being more pronounced in the posterior striatum and pallidum. In addition, it was checked that this neuroprotective effect of riluzole against systemic 3-nitropropionic acid did not result from a decreased bioavailability of the neurotoxin or a direct action of riluzole on 3-nitropropionic acid-induced inhibition of succinate dehydrogenase. We found that riluzole significantly decreased by 48% the size of striatal lesions produced by stereotaxic intrastriatal injection of malonate, a reversible succinate dehydrogenase inhibitor. Furthermore, the inhibition of cortical and striatal succinate dehydrogenase activity induced by systemic 3-nitropropionic acid was left unchanged by riluzole administration. The present results, consistent with a beneficial effect of riluzole in amyotrophic lateral sclerosis, suggest that this compound may be useful in the treatment of chronic neurodegenerative diseases. |
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Authors:
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M C Guyot; S Palfi; J M Stutzmann; M Mazière; P Hantraye; E Brouillet |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Neuroscience Volume: 81 ISSN: 0306-4522 ISO Abbreviation: Neuroscience Publication Date: 1997 Nov |
Date Detail:
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Created Date: 1997-11-06 Completed Date: 1997-11-06 Revised Date: 2005-11-17 |
Medline Journal Info:
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Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 141-9 Citation Subset: IM |
Affiliation:
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Service Hospitalier Frédéric Joliot, Unité de Recherche Associée 2210 Commissariat à l'Energie Atomique-Centre National de la Recherche Scientifique, Département de Recherche Médicale, Orsay, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antihypertensive Agents / toxicity* Corpus Striatum / pathology, physiopathology* Injections, Intraperitoneal Male Malonates / toxicity Microinjections Movement Disorders / drug therapy*, mortality Neuroprotective Agents / pharmacology* Neurotoxins / toxicity Nitro Compounds Propionic Acids / toxicity* Rats Rats, Sprague-Dawley Riluzole / pharmacology* Succinate Dehydrogenase / antagonists & inhibitors Survival Analysis |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Malonates; 0/Neuroprotective Agents; 0/Neurotoxins; 0/Nitro Compounds; 0/Propionic Acids; 141-82-2/malonic acid; 1744-22-5/Riluzole; 504-88-1/3-nitropropionic acid; EC 1.3.99.1/Succinate Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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