Quantification of Lipoic Acid Induced Changes in Nrf2-Mediated Stress Response Public Deposited

http://ir.library.oregonstate.edu/concern/undergraduate_thesis_or_projects/3n2041439

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  • As organisms age they lose the ability to respond to both exogenous and endogenous stresses, therefore placing them at a greater risk for the development of many diseases. The transcription factor Nrf2 is responsible for the induction of many oxidative stress response genes and therefore 3proteins. Additionally, Nrf2-mediated stress response has been shown to decline with age. In rats and mice, the compound α-lipoic acid (LA) appears to reverse this age related loss, however the effectiveness of LA in humans has not yet been demonstrated. In this study salivary levels of the Nrf2-mediated protein aldehyde dehydrogenase 3A1 (ALDH3A1) were measured during both LA and placebo supplementation in human subjects. Results indicate that ALDH3A1 levels show a delayed increase as a result of LA. In addition to ALDH3A1 levels in saliva, expression Nrf2-regulated genes heme oxygenase 1 (HO1) and γ-glutamylcysteine ligase (GCLC) in white blood cells were measured via RT-qPCR. GCLC expression in white blood cells did not change following LA supplementation, but HO1 levels decreased, which may be indicative of an overall increase in glutathione (GSH). This study was part of a small, pilot clinical trial and the data obtained from this study suggest possible method in which LA induced changes in Nrf2-mediated stress response can be studied in humans.
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