Antioxidants in Translational Medicine

Abstract

Significance: It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent evidence points even to health risks, in particular for supplements of lipophilic antioxidants. Recent Advances: The biological impact of ROS depends not only on their quantities but also on their chemical nature, (sub)cellular and tissue location, and the rates of their formation and degradation. Moreover, ROS serve important physiological functions; thus, inappropriate removal of ROS may cause paradoxical reductive stress and thereby induce or promote disease. Critical Issues: Any recommendation on antioxidants must be based on solid clinical evidence and patient-relevant outcomes rather than surrogate parameters. Future Directions: Such evidence-based use may include site-directed application, time-limited high dosing, (functional) pharmacological repair of oxidized biomolecules, and triggers of endogenous antioxidant response systems. Ideally, these approaches need guidance by patient stratification through predictive biomarkers and possibly imaging modalities. Antioxid. Redox Signal. 23, 1130–1143.

Reactive Oxygen Species Can Provide Atheroprotection via NOX4-Dependent Inhibition of Inflammation and Vascular Remodeling

“…Oxidative stress has been postulated to be a key mediator of endothelial dysfunction and vascular disease; however, all clinical therapies addressing this by the use of antioxidants have failed by being ineffective or even causing harm. 39 It is hypothesized that this is because of the fact that ROS do not have exclusively negative effects but also serve essential signaling functions, for example, in innate immunity, hormone synthesis, and angiogenesis. The key for therapeutic exploitation of ROS will thus be to differentiate between disease-triggering and physiological sources of ROS that should rather be left untouched.…”

Repurposing the NRF2 Activator Dimethyl Fumarate as Therapy Against Synucleinopathy in Parkinson's Disease

“…Finally, dementia is becoming one of the most difficult symptoms to palliate in late PD. However, although this issue has not yet been addressed in a preclinical model of PD, there is strong evidence indicating that the NRF2 might protect the cholinergic system in Alzheimer's disease mouse models (40,62).…”

Taking up the cudgels for the traditional reactive oxygen and nitrogen species detection assays and their use in the cardiovascular system

“…for different Nox isoforms) [20], or even repair the resulting oxidative damage (e.g. activators and stimulators of oxidized soluble guanylyl cyclase) thus leaving important cellular redox signaling mechanisms intact [13,21]. The failure of classical antioxidants to fight successfully oxidative stress associated diseases stresses the point that we have to learn more about the sources of ROS and RNS, their interaction, discrimination between beneficial (physiological) redox signaling and detrimental (pathophysiological) oxidative damage pathways.…”