Protective effect of adenosine and purine nucleos(t)ides against the death by hydrogen peroxide and glucose deprivation in rat primary astrocytes

Abstract Previously, we have shown that hydrogen peroxide (H 2 O 2 ) and glucose deprivation (GD) induced ATP loss and cell death in astrocytes. Here, we reported that adenosine and related purine nucleos(t)ides recovered cellular ATP level and completely prevented the cell death in rat primary astrocytes co-treated with H 2 O 2 and glucose deprivation. Time- and concentration-dependently, H 2 O 2 induced cell death and ATP loss in glucose-deprived astrocytes. Adenosine or ATP prevented both astrocytic death and ATP loss caused by H 2 O 2 /GD in dose-dependent manner. Further, inhibition of adenosine deamination or transport with erythro-9-(-hydroxy-3-nonyl)adenosine or S -(4-nitrobenzyl)-6-thioinosine largely attenuated the protective effect of adenosine. Other purine nucleos(t)ides such as inosine, guanosine, ADP, AMP, ITP and GTP also showed similar protective effects. Adenosine or ATP also blocked the mitochondrial dysfunction and glutathione (GSH) depletion in H 2 O 2 -treated glucose-deprived astrocytes. The present results suggest that adenosine and related purine nucleos(t)ides may protect astrocytes from H 2 O 2 and glucose deprivation induced the potentiated death by restoration of cellular ATP level.