Modulating the Antioxidant Response for Better Oxidative Stress-Inducing Therapies: How to Take Advantage of Two Sides of the Same Medal?

Abstract

Oxidative stress-inducing therapies are characterized as a specific treatment that involves the production of reactive oxygen and nitrogen species (RONS) by external or internal sources. To protect cells against oxidative stress, cells have evolved a strong antioxidant defense system to either prevent RONS formation or scavenge them. The maintenance of the redox balance ensures signal transduction, development, cell proliferation, regulation of the mechanisms of cell death, among others. Oxidative stress can beneficially be used to treat several diseases such as neurodegenerative disorders, heart disease, cancer, and other diseases by regulating the antioxidant system. Understanding the mechanisms of various endogenous antioxidant systems can increase the therapeutic efficacy of oxidative stress-based therapies, leading to clinical success in medical treatment. This review deals with the recent novel findings of various cellular endogenous antioxidant responses behind oxidative stress, highlighting their implication in various human diseases, such as ulcers, skin pathologies, oncology, and viral infections such as SARS-CoV-2.

Interplay of oxidative stress, cellular communication and signaling pathways in cancer

“…In the face of oxidative stress, tumor suppressor proteins act as pivotal regulators that dynamically modulate the cellular redox status [43]. These proteins can induce the transcription of antioxidant genes like glutathione peroxidases (GPx), superoxide dismutases (SOD), and catalases; simultaneously, they can suppress prooxidative genes that might otherwise exacerbate cellular stress and this dual regulatory ability enables tumor suppressor genes to create a finely tuned response that adapts to varying levels of oxidative stress [43,44]. p53 p53 is the chief regulator of programmed cell death and prevents tumorigenesis by facilitating the regulation of oxidative stress in cells.…”

Effects of Nitro-Oxidative Stress on Biomolecules: Part 1—Non-Reactive Molecular Dynamics Simulations

“…Increased entry of RONS into the cell disrupts the balance between intracellular RONS levels and the antioxidant system, resulting in oxidative stress [ 51 ]. This oxidative stress can damage proteins, lipids, and DNA, affecting crucial interactions such as protein-protein, protein-lipid, and DNA-protein interactions, and disturbing the normal function of cell organelles [ 32 , 52 , 53 , 54 , 55 , 56 , 57 ]. The membrane also maintains membrane proteins, which have various functions in the cell, including membrane receptors, transport proteins, membrane enzymes, and cell adhesion molecules [ 58 ].…”

The Activation of PPARγ by (2Z,4E,6E)-2-methoxyocta-2,4,6-trienoic Acid Counteracts the Epithelial–Mesenchymal Transition Process in Skin Carcinogenesis

“…Here we reproduced some experiments with A02 to evaluate its potential to exert a similar effect. The treatment with the compound (10, 50, 90 μM) for 6 h significantly increased the mRNA expression level of CATALASE ( CAT ), HEME-OXIGENASE 1 ( HO-1) , and NAD(P)H QUINONE DEHYDROGENASE 1 ( NQO1) ( Figure 1 D), three key enzymes involved in cellular defense against oxidative stress [ 66 , 67 ]. The Western blot analysis of catalase confirmed the gradual induction of the protein after 24 h of treatment ( Figure 1 E).…”