Hormesis and Oxidative Distress: Pathophysiology of Reactive Oxygen Species and the Open Question of Antioxidant Modulation and Supplementation

Abstract

Alterations of redox homeostasis leads to a condition of resilience known as hormesis that is due to the activation of redox-sensitive pathways stimulating cell proliferation, growth, differentiation, and angiogenesis. Instead, supraphysiological production of reactive oxygen species (ROS) exceeds antioxidant defence and leads to oxidative distress. This condition induces damage to biomolecules and is responsible or co-responsible for the onset of several chronic pathologies. Thus, a dietary antioxidant supplementation has been proposed in order to prevent aging, cardiovascular and degenerative diseases as well as carcinogenesis. However, this approach has failed to demonstrate efficacy, often leading to harmful side effects, in particular in patients affected by cancer. In this latter case, an approach based on endogenous antioxidant depletion, leading to ROS overproduction, has shown an interesting potential for enhancing susceptibility of patients to anticancer therapies. Therefore, a deep investigation of molecular pathways involved in redox balance is crucial in order to identify new molecular targets useful for the development of more effective therapeutic approaches. The review herein provides an overview of the pathophysiological role of ROS and focuses the attention on positive and negative aspects of antioxidant modulation with the intent to find new insights for a successful clinical application.

Glutathione in cancer progression and chemoresistance: an update

“…The pathogenesis of several human diseases including cancer is characterised by alterations of intracellular redox homeostasis [Traverso N, Ricciarelli R et al 2013;Nitti M, Marengo B et al 2022].…”

“…Although cancer cells prefer aerobic glycolysis (Warburg effect), in order to satisfy their energy demands, under pro-oxidant conditions their metabolism can shift towards oxidative phosphorylation (OXPHOS), that is a dynamic and reversible process strongly involved in cancer progression and therapy resistance [Nitti M, Marengo B et al 2022]. In this connection, our recent study demonstrated that the inhibition of protein kinase C- (PKC-), by favouring the switch from OXPHOS to aerobic glycolysis, is able to reduce GSH levels and stimulate ferroptosis (see next paragraph) of chemoresistant neuroblastoma stem cells [Monteleone L, Speciale A et al 2021].…”

“…In fact, the anticancer strategy is often based on the induction of oxidative stress through the administration of pro-oxidant chemotherapeutic drugs or ionizing radiation [Pelicano H, Carney D et al 2004;Holley AK, Miao L et al 2014]. Unfortunately, these approaches, after an initial success, lead to the onset of chemoresistance due to the increase of antioxidant defense [Kim EK, Jang M et al 2019;Domenicotti C, Marengo B 2022].…”

On the Potential Role of the Antioxidant Couple Vitamin E/Selenium Taken by the Oral Route in Skin and Hair Health

“…To reconcile both deleterious and physiological aspects of ROS, Sies and Jones [ 30 ] defined OS as an imbalance between reactive oxidative species or ROS and antioxidants in favor of the formers, leading to a signaling disruption as a consequence of oxidative damages to lipids, and DNA evidenced by the measurement of proteins. A third interesting and novel concept is adaptive oxidative stress or hormesis ( Figure 1 ) defined as a phenomenon in which ROS produced in moderate amounts had beneficial effects to living organisms [ 31 , 32 , 33 ].…”

Effects of Feeding with Non-Autoclaved and Autoclaved Fructose-Arginine Mixture on Stress Resistance of Drosophila Melanogaster

“…If these products undergo certain modifications and thereby stabilize, they are converted into advanced glycation endproducts (AGEs) (Semchyshyn, 2013). Both Maillard products and AGEs are capable of inducing oxidative stress (Hegele et al, 2009;Nitti et al, 2022;Schmitt et al, 2006;Van Nguyen, 2006b). Oxidative stress results in tissue damage and accelerates aging (Liguori et al, 2018).…”