ABSTRACT

Introduction...................................................................................................... 461 a-Lipoic Acid: Use as an Antioxidant ............................................................ 463 Selenotrisulfides and Their Role in Selenoprotein Synthesis .......................... 464 Chemistry of Selenotrisulfides ..................................................................... 464 Selenoprotein Synthesis ............................................................................... 465 Selenotrisulfides as Intermediates in Selenium Metabolism ....................... 466 Effect of Selenotrisulfides on Cellular Targets............................................ 466 Uptake of Selenotrisulfides and Identification In Vivo ............................... 467

Selenotrisulfide Derivative of a-Lipoic Acid .................................................. 467 Synthesis and Initial Characterization.......................................................... 467 Rationale for Topical Application of Selenium........................................... 468 Efficiency of Selenium Utilization and Delivery from LASe ..................... 469

Conclusions and Future Directions.................................................................. 469 Abbreviations ................................................................................................... 470 References ........................................................................................................ 470

Damage caused by reactive oxygen species (ROS) has been linked to cancer due to oxidative modifications to DNA, and it is also well established that ROS can contribute to degenerative diseases and aging. The use of small molecule antioxidants to prevent the development of cancer as well as to postpone the natural effects of aging has expanded in recent years, both in model cell culture systems

as well as in animal studies. a-Lipoic acid (LA) has shown great promise as a lipid soluble antioxidant, especially in studies focused on oxidative stress and aging in the brain [1,2]. Recent analysis of the safety of LA indicates that oral administration yields no significant side effects in long-term exposure studies in animals [3,4].