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 Ca-45(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 Ca-45(2+) uptake. Diphenyl diselenide and diphenyl ditelluride had no effects on glutamate-driven Ca-45(2+) influx. Diphenyl telluride (100-400 mu M) decreased and ebselen (100-400 mu M) completely blocked the glutamate-driven Ca-45(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 mu M) 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. (c) 2005 Elsevier B.V All rights reserved.