Protective Effect of ARE-Inducing Phenol Antioxidant TS-13 in Chronic Inflammation

Abstract

The protective effect of partially substituted monophenol TS-13 inducing the Nrf2/Keap1/ARE signaling system was studied on the model of chronic inflammation in vivo. It was found that during simulation of inflammation in an air pouch lined with synovial-like membrane, TS-13 did not affect the exudate volume, protein content, and cell count, but significantly reduced the intensity of oxidative metabolism in leukocytes of the exudate. In rheumatoid polyarthritis induced by heterologous collagen, TS-13 reduced the severity of clinical signs of inflammation only at the early stages, but inhibited H2O2 generation by monocytes and, partially, by blood neutrophils. These results suggest that the phlogolytic effect of the redox sensitive Nrf2/Keap1/ARE signaling system is less pronounced in chronic immune-mediated inflammatory processes than in acute inflammation.

Antioxidative Stress Mechanisms behind Resveratrol: A Multidimensional Analysis

“…In the absence of external stimulation, Nrf2 is in the cytoplasm and binds to inactivated KEAP1. When ROS accumulates, there are conformational changes in KEAP1, making it disassociate from Nrf2 and translocate into the nucleus [69]. Musculoaponeurotic fibrosarcoma (Maf ) protein forms a heterodimer with Nrf2 and then combines with ARE to enhance the expression of downstream phase II antioxidant genes, producing antioxidant enzymes [70].…”

Optimizing an Antioxidant TEMPO Copolymer for Reactive Oxygen Species Scavenging and Anti-Inflammatory Effects in Vivo

“…The efficacy of antioxidant therapy in the air pouch model has been investigated by others. Drugs including 10-(6′-plastoquinonyl)­decyltriphenylphosphonium bromide (SkQ1), Cressa cretica extract, TS-13 (a tert -butyl phenol thiosulfonate), and atorvastatin have shown anti-inflammatory effects in this model. − These results are promising; however, all of these treatment options required prophylactic administration 1 h or 1–10 days (daily) before carrageenan injection to achieve therapeutic efficacy. In contrast, coadministration of our optimized TEMPO copolymer reduced both O 2 •– and TNFα levels in the air pouch by ∼90% and ∼83%, respectively.…”

Effect of Resveratrol on Markers of Oxidative Stress and Sirtuin 1 in Elderly Adults with Type 2 Diabetes

“…This effect is achieved through its interaction with erythroid-derived nuclear factor 2 (Nrf2), a transcription factor that modulates the expression of genes containing antioxidant response elements (AREs). The activation of the Nrf2/ARE pathway promotes the expression of antioxidant genes and stimulates the production of SOD, GPx and Cat enzymes, whose function is to eliminate ROS [ 58 , 59 ]. In this sense, it has been observed that RV activates Nrf2 through the activation of AMPK, which, in turn, stimulates the Nrf2/ARE pathway and, as a result, increases the production of antioxidant enzymes [ 58 , 59 , 60 ].…”

“…The activation of the Nrf2/ARE pathway promotes the expression of antioxidant genes and stimulates the production of SOD, GPx and Cat enzymes, whose function is to eliminate ROS [ 58 , 59 ]. In this sense, it has been observed that RV activates Nrf2 through the activation of AMPK, which, in turn, stimulates the Nrf2/ARE pathway and, as a result, increases the production of antioxidant enzymes [ 58 , 59 , 60 ]. In our study, we found a non-significant increase in SOD activity in EG1000 and a statistically significant decrease in the PG, which agrees with what was stated above, as well as with the results of two randomized double-blind clinical trials in which an increase in SOD activity was observed with RV treatments in doses of 500 and 800 mg/day, and a decrease in the activity of the enzyme was observed in groups treated with a placebo [ 55 , 61 ].…”