Effect of ebselen and organochalcogenides on excitotoxicity induced by glutamate in isolated chick retina

• Published in: Brain research 2005-03, Vol.1039 (1), p.146-152
• Main Authors: Centurião, Fernanda Bossemeyer, Corte, Cristiane Lenz Dalla, Paixão, Márcio Weber, Braga, Antônio Luís, Zeni, Gilson, Emanuelli, Tatiana, Rocha, João Batista Teixeira
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Azoles - pharmacology; Benzene Derivatives - pharmacology; Calcium; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - metabolism; Chalcogens; Chalcogens - pharmacology; Chick Embryo; Dose-Response Relationship, Drug; Excitotoxicity; Glutamate; Glutamic Acid; Nerve Degeneration - chemically induced; Nerve Degeneration - prevention & control; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotective Agents - pharmacology; Neurotoxins; Organometallic Compounds - pharmacology; Organoselenium Compounds - pharmacology; Oxidative Stress; Retina - drug effects; Retina - metabolism; Retina - pathology; Tellurium - pharmacology; Tetrazolium Salts - metabolism; Thiazoles - metabolism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2005.01.062

In this study, we evaluated the effects of three simple organochalcogenides (diphenyl diselenide, diphenyl ditelluride and diphenyl telluride) and ebselen on the glutamate-driven 45Ca 2+ 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 45Ca 2+ uptake. Diphenyl diselenide and diphenyl ditelluride had no effects on glutamate-driven 45Ca 2+ influx. Diphenyl telluride (100–400 μM) decreased and ebselen (100–400 μM) completely blocked the glutamate-driven 45Ca 2+ 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 μM) 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 Ca 2+ channels, other mechanisms are involved in the neuroprotection afforded by ebselen in this work, possibly its antioxidant properties.