In vitro efficacy of three lazaroids in a model of acute chemical neuronal hypoxia.
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 6h. 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.
Vignes
J R
JR
Université de Bordeaux 2, Service de Neurochirurgie A, Hôpital Pellegrin, 1 Place Amélie Raba-Léon, 33076 Bordeaux Cedex, France.
Hugon
J
J
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002839:Chromans / Q000627:therapeutic use*; D003124:Colorimetry; D003486:Cyanides / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011247:Pregnancy; D011281:Pregnatrienes / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002839:Chromans; D003486:Cyanides; D018696:Neuroprotective Agents; D010879:Piperazines; D011281:Pregnatrienes; C074965:U 74389F; C066382:U 78517F; C053356:U 74500A