Cadmium toxicity: unique cytoprotective properties of alpha tocopheryl succinate in hepatocytes

Rat hepatocyte suspensions were exposed to toxic concentrations of cadmium (Cd) in the presence and absence of unesterified alpha-tocopherol (T) or alpha-tocopheryl succinate (TS). The exogenous administration of TS completely protected hepatocytes from Cd-induced injury and lipid peroxidation. However, hepatocytes exposed to T were not protected from the toxic manifestations of cadmium even though this treatment resulted in a rapid marked accumulation of cellular T. The rate of cadmium uptake by hepatocytes was not significantly altered by exogenous TS or T treatment. These studies indicate that TS cytoprotection against Cd toxicity results not from alterations in Cd uptake or the accumulation of T but rather from the cellular presence of the intact TS molecule. The data also indicate that the depletion of cellular T is not the critical cellular event that is responsible for Cd-induced injury. Instead it appears that TS possess unique cytoprotective properties that intervene in the critical cellular events that lead to Cd toxicity. Thus, TS administration represents a promising new strategy for the mechanistic study and prevention of tissue damage resulting from Cd exposure.