Protective roles of glutathione in the toxicity of mercury and cadmium compounds to C6 glioma cells

Abstract

The neurotoxic effects of mercury (II) chloride, methylmercury (MeHg) and cadmium chloride on astrocytes were modelled using C6 glioma cell cultures. All three compounds were cytotoxic to these cells with an order of potency of cadmium > MeHg > mercury chloride. Addition of reduced glutathione (GSH) to the media protected the cells in all three cases, whereas depletion of GSH with l-buthionine- S,R-sulfoximine enhanced the toxicity of cadmium and mercury chloride but not MeHg. The effects of subcytotoxic concentrations of these compounds on intracellular GSH levels were assessed using chlorobimane staining. All three showed a similar type of effect—an initial depletion of GSH followed by an increase to levels greater than in untreated cells. For mercury chloride-exposed cells (0.37–3.7 μM), the initial depletion occurred over 4 hr with the cells recovering by 7 hr and increases in the GSH content seen after 24 hr. With cadmium or MeHg (0.04–4 μM), the initial depletion was more protracted, with treated cells having less GSH than control cells for 4–7 hr. Glutathione S-transferase activity in the cells was increased after 24 hr of exposure to all three metals to about 200% of control values. These results show that some components of the glutathione system in C6 glioma cells are activated after exposure to heavy metal compounds