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.
Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0662.
M W
MW
Fariss
D000818:Animals; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D015227:Lipid Peroxidation; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D002104:Cadmium; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D024505:Tocopherols