| Redox Status in Health and Disease Harry Van Goor1; Arno Bourgonje2; Amel Eman Abdulle2; Sanne Gordijn2; Udo Mulder2; Gerard Dijkstra2; Andreas Pasch3; 1UMCG, Groningen, Netherlands; 2UNIVERSITY MEDICAL CENTER GRONINGEN AND UNIVERSITY OF GRONINGEN, Groninge, Netherlands; 3JOHANNES KEPLER UNIVERSITY LINZ, Linz 4040, Austria; PAPER: 430/Oxidative/Regular (Oral) SCHEDULED: 15:55/Thu. 24 Oct. 2019/Zeus (55/Mezz. F) ABSTRACT: Oxidative stress is characterized by an excessive production of reactive oxygen species (ROS) and decreased antioxidant availability. It is considered as a major effector mechanism responsible for extensive cellular and molecular damage, perpetuating chronic inflammation and increased tissue destruction. Serum free thiols (R-SH, sulfhydryl groups) are considered as a robust and powerful read-out of the systemic in vivo reduction-oxidation (redox) status. Systemic oxidative stress is associated with decreased levels of reduced free thiols, since thiols are rapidly oxidized by circulating reactive species. Blood proteins, mainly albumin, harbor the largest amount of redox-active thiol groups (approximately 75% of the total thiol pool). Typically, high extracellular concentrations of reduced free thiols are representative of a healthy redox status. We have examined systemic free thiol levels in a variety of (inflammatory) disease conditions, including pregnancy related, cardiovascular, renal, metabolic and rheumatological diseases. All these studies show a positive association between free thiol levels and favorable disease outcomes. Inversely, decreased free thiols have been linked to cardiovascular risk factors, such as ageing, obesity and alcohol consumption. In patient with Crohn’s disease in clinical remission systemic free thiols were still markedly reduced levels indicating the sensitivity of the Redox system as biomarker for (latent) disease. We evaluated free thiols in patients with inflammatory bowel disease and found them to be a strongly discriminating biomarker for endoscopic disease activity in IBD, even superiorly to classical fecal calprotectin levels. In a prospective clinical study that evaluated effects of dietary intake of the anti-oxidant riboflavin (vitamin B2) in Crohn’s disease, we observed significant improvement of systemic redox status after 3 weeks of riboflavin supplementation. This study highlights the potential significance of free thiols as therapeutic target of the redox signaling network in disease conditions. Finally, In a large population-based cohort (n=6000), the redox status was inversely associated with the risk of cardiovascular events and all-cause mortality (10 year follow up). All these data highlight the potential significance and clinical relevance of the Redox status as modifiable biomarker in both health and disease. |
