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Make a choice prof. dr. S.J.L. Bakker Prof. dr. H. van Goor drs. A.R. Bourgonje

Project properties

Title	The Effects of Lifestyle-, Diet- and Antioxidant Interventions on the Systemic Redox Status in Health and Disease
Keywords	chronic disease oxidative stress biomarkers
Researchers	prof. dr. S.J.L. Bakker Prof. dr. H. van Goor drs. A.R. Bourgonje
Nature of the research	Prospective and retrospective cohort studies
Fields of study	epidemiology and statistics internal medicine nephrology

Background / introduction

Oxidative stress is characterized by an imbalance between the production of reactive oxygen species (ROS, oxidants) and antioxidant availability in favor of the oxidants. Oxidative stress plays a pivotal role in a variety of human diseases. (1) In general, oxidative stress is considered as a major disease mechanism responsible for extensive cellular and molecular damage, perpetuation of inflammatory reactions and tissue destruction. ROS and related compounds are gaining increasing interest in literature as biomarkers for virtually all conditions in which “redox stresses” are involved. Recently, we investigated the potential value of serum free thiols (R-SH, sulfhydryl groups) as a predictive biomarker for disease outcome in health and in a variety of disease conditions. (2-4) Free thiols are considered a robust and reliable read-out of systemic levels of oxidative stress. Typically, systemic oxidative stress is associated with decreased free thiol levels, whereas high levels of free thiols are representative of a favorable redox status. (1) Recently, we found that serum free thiols were able to predict mortality and the occurrence of cardiovascular disease in otherwise healthy individuals from a large population-based cohort. (2,3) In a recent follow-up study, we convincingly demonstrated that higher levels of free thiols (reflecting less oxidative stress) were associated with a decreased risk of developing chronic kidney disease (CKD), again in subjects from the general population. (4) In previous studies, we observed similar associations to disease outcome and disease prognosis. For instance, in a study in renal transplant recipients, serum free thiols were associated with improved patient and graft survival, and in a study consisting of patients with heart failure, free thiols demonstrated were strongly associated with disease severity indices and prognosis. (5-7) Overall, these results indicated that the use of redox biomarkers may be highly useful as potentially predictive tools in future translational research. Furthermore, these results are particularly intriguing as serum free may form a potential target for therapy, which makes them even more interesting and valuable to study. Our next studies will now focus on the effects of lifestyle-, diet-, antioxidant, and anti-inflammatory drugs and interventions on the systemic redox status in health and disease. By doing so, we aim to define whether reduction in oxidative stress associates with beneficial treatment effects. Our ultimate goal is to design personalized redox medicine, decreasing the oxidative burden without affecting the physiological role of ROS.

Research question / problem definition

In this research, we have several questions that we would like to answer: • What is the value redox biomarkers for disease activity in oxidative stress-mediated human diseases? • What are the effects of lifestyle-, diet-, antioxidant and anti-inflammatory interventions on the systemic redox status in health and in disease conditions? • What is the predictive value of redox biomarkers with regard to treatment responses and disease prognosis in health and in disease conditions?

Workplan

The student will help to discover the role of the human redox system in oxidative stress-mediated diseases and to study the effects of lifestyle, diet and treatments on its dynamics. A large amount of data has already been collected that is ready to be explored and additional data will be collected to study the role of redox biomarkers as monitoring tools for treatment effects and as predictive tools for disease-specific outcomes and disease prognosis. These studies will be mainly clinically-oriented and of translational origin, but an easy shift could be made towards more fundamental research (if preferred). The student will learn a lot about disease mechanisms and develop skills for data analysis and data interpretation.

References

(1) Cortese-Krott MM, Koning A, Kuhnle GGC, Nagy P, Bianco CL, Pasch A, et al. The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine. Antiox Redox Signal 2017;27(10):684-712. (2) Bourgonje MF, Bourgonje AR, Abdulle AE, Kieneker LM, la Bastide-van Gemert S, Gansevoort RT, Bakker SJL, Mulder DJ, Pasch A, Saleh J, Gordijn SJ, van Goor H. Systemic Oxidative Stress, Aging and the Risk of Cardiovascular Events in the General Female Population. Front Cardiovasc Med 2021;8:630543. (3) Abdulle AE, Bourgonje AR, Kieneker LM, Koning AM, la Bastide-van Gemert S, Bulthuis MLC, Dijkstra G, Faber KN, Dullaart RPF, Bakker SJL, Gans ROB, Gansevoort RT, Mulder DJ, Pasch A, van Goor H. Serum free thiols predict cardiovascular events and all-cause mortality in the general population: a prospective cohort study. BMC Med 2020;18(1):130. (4) Bourgonje AR, Abdulle AE, Bourgonje MF, Binnenmars HS, Gordijn SJ, Bulthuis MLC, la Bastide-van Gemert S, Kieneker LM, Gansevoort RT, Bakker SJL, Mulder DJ, Pasch A, de Borst MH, van Goor H. Serum free sulfhydryl status associates with new-onset chronic kidney diseae in the general population. Redox Biol 2021;48:102211. (5) Frenay AS, de Borst MH, Bachtler M, Tschopp N, Keyzer CA, van den Berg E, Bakker SJL, Feelisch M, Pasch A, van Goor H. Serum free sulfhydryl status is associated with patient and graft survival in renal transplant recipients. Free Radic Biol Med 2016;99:345-51. (6) Koning AM, Meijers WC, Pasch A, Leuvenink HGD, Frenay AS, Dekker MM, Feelisch M, de Boer RA, van Goor H. Serum free thiols in chronic heart failure. Pharmacol Res 2016;111:452-58. (7) Bourgonje AR, Gabriëls RY, de Borst MH, Bulthuis MLC, Faber KN, van Goor H, Dijkstra G. Serum Free Thiols Are Superior to Fecal Calprotectin in Reflecting Endoscopic Disease Activity in Inflammatory Bowel Disease. Antioxidants (Basel) 2019;8(9):351.