In vitro efficacy of three lazaroids in a model of acute chemical neuronal hypoxia

• Published in: Neuroscience letters 2006-10, Vol.407 (2), p.171-175
• Main Authors: Vignes, J.R., Hugon, J.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Hypoxia - drug effects; Cell Hypoxia - physiology; Cells, Cultured; Chromans - therapeutic use; Colorimetry; Cyanide; Cyanides - toxicity; Dose-Response Relationship, Drug; Female; Free radical scavengers; Fundamental and applied biological sciences. Psychology; Lazaroids; Lipid peroxidation; Neurons - drug effects; Neuroprotection; Neuroprotective Agents - therapeutic use; Oxidative stress; Piperazines - therapeutic use; Pregnancy; Pregnatrienes - therapeutic use; Rats; Rats, Sprague-Dawley; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2006.08.023

Free radicals are highly reactive chemicals containing an unpaired electron and are normally produced by the cellular metabolism. But the excessive production of free radicals by oxidative stress is engaged in a large variety of diseases. The goal of this work was to determine the neuroprotective effect of free radical scavengers in an acute in vitro model of neuronal hypoxia. Primary cultures of cortical neurons of rats were exposed to 0.5 mM sodium cyanide for 6 h. Neuron death was evaluated with a lactate dehydrogenase assay. This mortality was up to 66.5% in cultures exposed to 0.5 mM sodium cyanide compared to non-exposed control cultures. Three lazaroids (U-74500A, U-74389G, U-83836E), were added to cultures, at different concentrations (10 −7–10 −5 M), simultaneously with cyanide, during 6 h. These agents caused a reduction in neuronal death, compared to exposed cultures. Efficacy varied with lazaroid compounds and U-74500A decreased neuronal death to 37–23.5%, U-74389G to 37–32%, and U-83836E to 42–33%. These results suggest a partial neuroprotective effect of free radical scavengers since lipid peroxidation is a key cellular event in neuronal injury, and its inhibition with lazaroids could help to reduce brain ischaemic lesions.