a-Lipoic Acid on Human Erythrocytes and Lymphocytes

Derick Han, Lucia Marcocci, Garry Handelman, and Lester Packer

Department of Molecular and Cell Biology, University of California Lipoic acid is used therapeutically in Germany for diabetes polyneuropathy and is a nutritional supplement in the United States, Because lipoate is present in the bloodstream after oral administration, we examined the effect of lipoate on human erythrocytes and lymphocytes in vitro. The administration of lipoate (2O-lOOuM) to erythrocytes in vitro results in two major changes. First, lipoate is reduced to dihydrolipoate, which has been shown to be a powerful reducing agent. Secondly, lipoate causes a Small increase in intracellular levels of reduced glutathione. Treatment with a 100 uM lipoate causes a 14.3% increase in glutathione in 24 hours. Similar results have been obtained with a human T-lymphocyte Jurkat cell line where administration of lipoate to dihydrolipoate and a 46% elevation of glutathione levels in 24 hours. These results indicate that the physiologic administration in lipoate will result in a more reduced status in blood due to the likelihood of both erythrocytes and lymphocytes reducing lipoate to dihydrolipoate and due the elevation of intracellular glutathione levels. Many disorders like HIV and diabetes are associated with oxidative stress, glutathione depletion and a shift in redox status of plasma to a more oxidized state. Lipoic acid may be potentially useful as a therapeutic agent in these disorders due to its combined ability to generate a more reduced extracellular environment and its ability bolster cell glutathione levels.