Quantification of Lipoic Acid Induced\ud Changes in Nrf2-Mediated Stress Response

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