ALPHA-TOCOPHEROL AMELIORATES OXIDANT INJURY IN ISOLATED COPPER-OVERLOADED RAT HEPATOCYTES

The objective of this study was to determine the role of oxidant stres s in cell injury produced by in vivo copper overload of isolated rat h epatocytes. Rats were maintained on diets with elevated or normal copp er content, and hepatocytes were isolated and then incubated for 4 h i n physiologic buffer at physiologic oxygen saturations. In hepatocytes from copper-overloaded rats, a significant loss of cell viability (tr ypan blue exclusion) over 4 h compared with control cells was associat ed with a significant increase in lipid peroxidation (thiobarbituric a cid-reacting substances). Incubation of copper-overloaded hepatocytes with the copper chelator, 2,3,2-tetramine, had a partial protective ef fect. Incubation with D-alpha-tocopheryl succinate completely ameliora ted the copper-induced changes in viability and lipid peroxidation. We conclude that antioxidants may protect the isolated hepatocyte from c opper toxicity and should be explored as potential therapeutic agents in states of copper overload.