Glutathione can efficiently prevent direct current-induced cytotoxicity.

We have reported that direct current (DC) with antibacterial agents used in iontophoresis for root canal disinfection induced host cell necrotic cytotoxicity, and this DC-induced cytotoxicity may be because of generated free radicals and metal ions eluted from metal electrodes. Iontophoresis is still used in some cases, and thus it is necessary to consider how we may prevent DC-induced cytotoxicity of host cells of periapical lesions. Thus, we compared the protective effects of various antioxidants on the DC-induced cytotoxicity against host cells. N-acetyl-L-cysteine and glutathione (GSH) efficiently prevented DC-induced cytotoxicity against human polymorphonuclear cells (PMNs) (p < 0.01). The DC-induced cytotoxicity against PMNs was significantly enhanced by buthionine sulfoximine (p < 0.05), an inhibitor of GSH synthesis, and its effect was rescued by adding the exogenous GSH (p < 0.01). In addition, DC treatment reduced the intracellular GSH levels in a time-dependent manner (p < 0.05). Transmission electron microscopy showed that the DC induced the intense vacuolization and accumulation of cellular debris in autophagolysosomes, and these morphological changes were blocked by adding exogenous GSH. These results suggest that GSH, a thiol antioxidant, effectively prevents the DC-induced cytotoxicity.