Abstract
The objective of this study was to determine the role of oxidant stress in cell injury produced by in vivo copper overload of isolated rat hepatocytes. Rats were maintained on diets with elevated or normal copper content, and hepatocytes were isolated and then incubated for 4 h in physiologic buffer at physiologic oxygen saturations. In hepatocytes from copper-overloaded rats, a significant loss of cell viability (trypan blue exclusion) over 4 h compared with control cells was associated with a significant increase in lipid peroxidation (thiobarbituric acid-reacting substances). Incubation of copper-overloaded hepatocytes with the copper chelator, 2,3,2-tetramine, had a partial protective effect. Incubation with D-α-tocopheryl succinate completely ameliorated the copper-induced changes in viability and lipid peroxidation. We conclude that antioxidants may protect the isolated hepatocyte from copper toxicity and should be explored as potential therapeutic agents in states of copper overload.
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Abbreviations
- TBARS:
-
thiobarbituric acid-reducing substances
- O˙2:
-
superoxide
- OH·:
-
hydroxyl radical
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Acknowledgements
The authors thank Kenneth Allen, Ph.D., for providing the 2,3,2-tetramine, K. Michael Hambidge, M.D., for the copper analyses, and Joanna Lantzy and Cindy Wyman for typing the manuscript.
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Supported in part by National Institutes of Health Grants (R01DK38446, 1P30AM34914, R01DK12432) and the Abby Bennett Liver Research Fund.
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Sokol, R., Mckim, J. & Devereaux, M. α-Tocopherol Ameliorates Oxidant Injury in Isolated Copper-Overloaded Rat Hepatocytes. Pediatr Res 39, 259–263 (1996). https://doi.org/10.1203/00006450-199602000-00012
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DOI: https://doi.org/10.1203/00006450-199602000-00012
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