Antioxidant Metabolism Pathways in Vitamins, Polyphenols, and Selenium: Parallels and Divergences.

Free radicals (FRs) are unstable molecules that cause reactive stress (RS), an imbalance between reactive oxygen and nitrogen species in the body and its ability to neutralize them. These species are generated by both internal and external factors and can damage cellular lipids, proteins, and DNA. Antioxidants prevent or slow down the oxidation process by interrupting the transfer of electrons between substances and reactive agents. This is particularly important at the cellular level because oxidation reactions lead to the formation of FR and contribute to various diseases. As we age, RS accumulates and leads to organ dysfunction and age-related disorders. Polyphenols; vitamins A, C, and E; and selenoproteins possess antioxidant properties and may have a role in preventing and treating certain human diseases associated with RS. In this review, we explore the current evidence on the potential benefits of dietary supplementation and investigate the intricate connection between SIRT1, a crucial regulator of aging and longevity; the transcription factor NRF2; and polyphenols, vitamins, and selenium. Finally, we discuss the positive effects of antioxidant molecules, such as reducing RS, and their potential in slowing down several diseases.

Electrophilic Compounds in the Human Diet and Their Role in the Induction of the Transcription Factor NRF2.

The phrase "Let food be thy medicine…" means that food can be a form of medicine and medicine can be a form of food; in other words, that the diet we eat can have a significant impact on our health and well-being. Today, this phrase is gaining prominence as more and more scientific evidence suggests that one's diet can help prevent and treat disease. A diet rich in fruits, vegetables, whole grains, and lean protein can help reduce the risk of heart disease, cancer, diabetes, and other health problems and, on the other hand, a diet rich in processed foods, added sugars, and saturated fats can increase the risk of the same diseases. Electrophilic compounds in the diet can have a significant impact on our health, and they are molecules that covalently modify cysteine residues present in the thiol-rich Keap1 protein. These compounds bind to Keap1 and activate NRF2, which promotes its translocation to the nucleus and its binding to DNA in the ARE region, triggering the antioxidant response and protecting against oxidative stress. These compounds include polyphenols and flavonoids that are nucleophilic but are converted to electrophilic quinones by metabolic enzymes such as polyphenol oxidases (PPOs) and sulfur compounds present in foods such as the Brassica genus (broccoli, cauliflower, cabbage, Brussel sprouts, etc.) and garlic. This review summarizes our current knowledge on this subject.

Chemistry of Hydrogen Sulfide-Pathological and Physiological Functions in Mammalian Cells.

Hydrogen sulfide (H2S) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). The aim of this review is to provide an overview of the formation of hydrogen sulfide (H2S) in the human body. H2S is synthesized by enzymatic processes involving cysteine and several enzymes, including cystathionine-ß-synthase (CBS), cystathionine-γ-lyase (CSE), cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (3MST) and D-amino acid oxidase (DAO). The physiological and pathological effects of hydrogen sulfide (H2S) on various systems in the human body have led to extensive research efforts to develop appropriate methods to deliver H2S under conditions that mimic physiological settings and respond to various stimuli. These functions span a wide spectrum, ranging from effects on the endocrine system and cellular lifespan to protection of liver and kidney function. The exact physiological and hazardous thresholds of hydrogen sulfide (H2S) in the human body are currently not well understood and need to be researched in depth. This article provides an overview of the physiological significance of H2S in the human body. It highlights the various sources of H2S production in different situations and examines existing techniques for detecting this gas.

Chemical Insights into Oxidative and Nitrative Modifications of DNA.

This review focuses on DNA damage caused by a variety of oxidizing, alkylating, and nitrating species, and it may play an important role in the pathophysiology of inflammation, cancer, and degenerative diseases. Infection and chronic inflammation have been recognized as important factors in carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from inflammatory and epithelial cells, and result in the formation of oxidative and nitrative DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. Cellular DNA is continuously exposed to a very high level of genotoxic stress caused by physical, chemical, and biological agents, with an estimated 10,000 modifications occurring every hour in the genetic material of each of our cells. This review highlights recent developments in the chemical biology and toxicology of 2'-deoxyribose oxidation products in DNA.

Superoxide Anion Chemistry-Its Role at the Core of the Innate Immunity.

Classically, superoxide anion O2•- and reactive oxygen species ROS play a dual role. At the physiological balance level, they are a by-product of O2 reduction, necessary for cell signalling, and at the pathological level they are considered harmful, as they can induce disease and apoptosis, necrosis, ferroptosis, pyroptosis and autophagic cell death. This revision focuses on understanding the main characteristics of the superoxide O2•-, its generation pathways, the biomolecules it oxidizes and how it may contribute to their modification and toxicity. The role of superoxide dismutase, the enzyme responsible for the removal of most of the superoxide produced in living organisms, is studied. At the same time, the toxicity induced by superoxide and derived radicals is beneficial in the oxidative death of microbial pathogens, which are subsequently engulfed by specialized immune cells, such as neutrophils or macrophages, during the activation of innate immunity. Ultimately, this review describes in some depth the chemistry related to O2•- and how it is harnessed by the innate immune system to produce lysis of microbial agents.

Myeloid-Derived Suppressor Cells in Cancer and COVID-19 as Associated with Oxidative Stress.

Myeloid-derived suppressor cells MDSCs are a heterogeneous population of cells that expand beyond their physiological regulation during pathologies such as cancer, inflammation, bacterial, and viral infections. Their key feature is their remarkable ability to suppress T cell and natural killer NK cell responses. Certain risk factors for severe COVID-19 disease, such as obesity and diabetes, are associated with oxidative stress. The resulting inflammation and oxidative stress can negatively impact the host. Similarly, cancer cells exhibit a sustained increase in intrinsic ROS generation that maintains the oncogenic phenotype and drives tumor progression. By disrupting endoplasmic reticulum calcium channels, intracellular ROS accumulation can disrupt protein folding and ultimately lead to proteostasis failure. In cancer and COVID-19, MDSCs consist of the same two subtypes (PMN-MSDC and M-MDSC). While the main role of polymorphonuclear MDSCs is to dampen the response of T cells and NK killer cells, they also produce reactive oxygen species ROS and reactive nitrogen species RNS. We here review the origin of MDSCs, their expansion mechanisms, and their suppressive functions in the context of cancer and COVID-19 associated with the presence of superoxide anion •O2- and reactive oxygen species ROS.

Chlorine Dioxide: Friend or Foe for Cell Biomolecules? A Chemical Approach.

This review examines the role of chlorine dioxide (ClO2) on inorganic compounds and cell biomolecules. As a disinfectant also present in drinking water, ClO2 helps to destroy bacteria, viruses, and some parasites. The Environmental Protection Agency EPA regulates the maximum concentration of chlorine dioxide in drinking water to be no more than 0.8 ppm. In any case, human consumption must be strictly regulated since, given its highly reactive nature, it can react with and oxidize many of the inorganic compounds found in natural waters. Simultaneously, chlorine dioxide reacts with natural organic matter in water, including humic and fulvic acids, forming oxidized organic compounds such as aldehydes and carboxylic acids, and rapidly oxidizes phenolic compounds, amines, amino acids, peptides, and proteins, as well as the nicotinamide adenine dinucleotide NADH, responsible for electron and proton exchange and energy production in all cells. The influence of ClO2 on biomolecules is derived from its interference with redox processes, modifying the electrochemical balances in mitochondrial and cell membranes. This discourages its use on an individual basis and without specialized monitoring by health professionals.

Impact of Reactive Species on Amino Acids-Biological Relevance in Proteins and Induced Pathologies.

This review examines the impact of reactive species RS (of oxygen ROS, nitrogen RNS and halogens RHS) on various amino acids, analyzed from a reactive point of view of how during these reactions, the molecules are hydroxylated, nitrated, or halogenated such that they can lose their capacity to form part of the proteins or peptides, and can lose their function. The reactions of the RS with several amino acids are described, and an attempt was made to review and explain the chemical mechanisms of the formation of the hydroxylated, nitrated, and halogenated derivatives. One aim of this work is to provide a theoretical analysis of the amino acids and derivatives compounds in the possible positions. Tyrosine, methionine, cysteine, and tryptophan can react with the harmful peroxynitrite or •OH and •NO2 radicals and glycine, serine, alanine, valine, arginine, lysine, tyrosine, histidine, cysteine, methionine, cystine, tryptophan, glutamine and asparagine can react with hypochlorous acid HOCl. These theoretical results may help to explain the loss of function of proteins subjected to these three types of reactive stresses. We hope that this work can help to assess the potential damage that reactive species can cause to free amino acids or the corresponding residues when they are part of peptides and proteins.

The Role of Reactive Species on Innate Immunity.

This review examines the role of reactive species RS (of oxygen ROS, nitrogen RNS and halogen RHS) on innate immunity. The importance of these species in innate immunity was first recognized in phagocytes that underwent a "respiratory burst" after activation. The anion superoxide •O2- and hydrogen peroxide H2O2 are detrimental to the microbial population. NADPH oxidase NOx, as an •O2- producer is essential for microbial destruction, and patients lacking this functional oxidase are more susceptible to microbial infections. Reactive nitrogen species RNS (the most important are nitric oxide radical -•NO, peroxynitrite ONOO- and its derivatives), are also harmful to microorganisms, including bacteria, viruses, and parasites. Hypochlorous acid HOCl and hypothiocyanous acid HOSCN synthesized through the enzyme myeloperoxidase MPO, which catalyzes the reaction between H2O2 and Cl- or SCN-, are important inorganic bactericidal molecules, effective against a wide range of microbes. This review also discusses the role of antimicrobial peptides AMPs and their induction of ROS. In summary, reactive species RS are the heart of the innate immune system, and they are necessary for microbial lysis in infections that can affect mammals throughout their lives.

Hypochlorous Acid Chemistry in Mammalian Cells-Influence on Infection and Role in Various Pathologies.

This review discusses the formation of hypochlorous acid HOCl and the role of reactive chlorinated species (RCS), which are catalysed by the enzyme myeloperoxidase MPO, mainly located in leukocytes and which in turn contribute to cellular oxidative stress. The reactions of RCS with various organic molecules such as amines, amino acids, proteins, lipids, carbohydrates, nucleic acids, and DNA are described, and an attempt is made to explain the chemical mechanisms of the formation of the various chlorinated derivatives and the data available so far on the effects of MPO, RCS and halogenative stress. Their presence in numerous pathologies such as atherosclerosis, arthritis, neurological and renal diseases, diabetes, and obesity is reviewed and were found to be a feature of debilitating diseases.