Effect of ebselen and organochalcogenides on excitotoxicity induced by glutamate in isolated chick retina.
In this study, we evaluated the effects of three simple organochalcogenides (diphenyl diselenide, diphenyl ditelluride and diphenyl telluride) and ebselen on the glutamate-driven 45Ca2+ influx into chick embryonic retinal cells, as well as their effects on the excitotoxic injury in retina cells. None of the compounds tested interfered with basal 45Ca2+ uptake. Diphenyl diselenide and diphenyl ditelluride had no effects on glutamate-driven 45Ca2+ influx. Diphenyl telluride (100-400 microM) decreased and ebselen (100-400 microM) completely blocked the glutamate-driven 45Ca2+ influx (P < 0.01) into chick retinal explants. The assessment of neural injury was made spectrophotometrically by quantification of cellularly reduced MTT (3(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) 24 h after the beginning of glutamate exposure (8 h). Ebselen had no effects on retinal MTT reduction when co-incubated with glutamate for 8 h. However, when ebselen (100 and 400 microM) was co-incubated for 8 h with glutamate and remained in the incubation media until MTT evaluation (24 h after the beginning of incubation), it protected retinal cells against the decrease in MTT reduction induced by glutamate. These data indicate that besides its capacity of interacting with Ca2+ channels, other mechanisms are involved in the neuroprotection afforded by ebselen in this work, possibly its antioxidant properties.
Centurião
Fernanda Bossemeyer
FB
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brasil.
Corte
Cristiane Lenz Dalla
CL
Paixão
Márcio Weber
MW
Braga
Antônio Luís
AL
Zeni
Gilson
G
Emanuelli
Tatiana
T
Rocha
João Batista Teixeira
JB
D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D018011:Chalcogens / Q000494:pharmacology*; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid; D054833:Isoindoles; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins; D009942:Organometallic Compounds / Q000494:pharmacology*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013691:Tellurium / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D001393:Azoles; D001555:Benzene Derivatives; D015220:Calcium Channels; D018011:Chalcogens; D054833:Isoindoles; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C503220:diphenyl telluride; C434247:diphenylditelluride; C061132:diphenyldiselenide; D018698:Glutamic Acid; C042986:ebselen; C022616:thiazolyl blue; D013691:Tellurium; D002118:Calcium