Cytotoxic action of thimerosal on rat cerebellar granule cells

The effect of thimerosal, a preservative in vaccines, on rat cerebellar neurons was compared with that of methylmercury. Both agents at concentrations ranging from 0. 3μM to 10μM increased the intracellular concentration of Ca2+ ([Ca2+]i) in a dose-dependent manner. The potency of 10μM thimerosal to increase the [Ca2+]i was less than that of 10μM methylmercury. Their effects on the [Ca2+]i were greatly attenuated, but not completely suppressed, under external Ca2+-free condition, suggesting a possibility that both agents increase membrane Ca2+ permeability and release Ca2+ from intracellular Ca stores. The effect of 10μM thimerosal was not affected by application of 30μM L-cysteine whereas that of 10μM methylmercury was suppressed. The potency of thimerosal was similar to that of methylmercury in the presence of L-cysteine. Both agents at 1μM or more similarly decreased the cellular content of glutathione in a dose-dependent manner, suggesting an increase in oxidative stress. Results indicate that thimerosal exerts some cytotoxic actions on rat neurons and its potency is similar to that of methylmercury.