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Pharmacology & Therapeutics Dec 2021Initially adopted as a mucolytic about 60 years ago, the cysteine prodrug N-acetylcysteine (NAC) is the standard of care to treat paracetamol intoxication, and is... (Review)
Review
Initially adopted as a mucolytic about 60 years ago, the cysteine prodrug N-acetylcysteine (NAC) is the standard of care to treat paracetamol intoxication, and is included on the World Health Organization's list of essential medicines. Additionally, NAC increasingly became the epitome of an "antioxidant". Arguably, it is the most widely used "antioxidant" in experimental cell and animal biology, as well as clinical studies. Most investigators use and test NAC with the idea that it prevents or attenuates oxidative stress. Conventionally, it is assumed that NAC acts as (i) a reductant of disulfide bonds, (ii) a scavenger of reactive oxygen species and/or (iii) a precursor for glutathione biosynthesis. While these mechanisms may apply under specific circumstances, they cannot be generalized to explain the effects of NAC in a majority of settings and situations. In most cases the mechanism of action has remained unclear and untested. In this review, we discuss the validity of conventional assumptions and the scope of a newly discovered mechanism of action, namely the conversion of NAC into hydrogen sulfide and sulfane sulfur species. The antioxidative and cytoprotective activities of per- and polysulfides may explain many of the effects that have previously been ascribed to NAC or NAC-derived glutathione.
Topics: Acetylcysteine; Animals; Antioxidants; Humans; Hydrogen Sulfide; Sulfur
PubMed: 34171332
DOI: 10.1016/j.pharmthera.2021.107916 -
Oxidative Medicine and Cellular... 2019Goji berries (Lycium fruits) are usually found in Asia, particularly in northwest regions of China. Traditionally, dried goji berries are cooked before they are... (Review)
Review
Goji berries (Lycium fruits) are usually found in Asia, particularly in northwest regions of China. Traditionally, dried goji berries are cooked before they are consumed. They are commonly used in Chinese soups and as herbal tea. Moreover, goji berries are used for the production of tincture, wine, and juice. Goji berries are high antioxidant potential fruits which alleviate oxidative stress to confer many health protective benefits such as preventing free radicals from damaging DNA, lipids, and proteins. Therefore, the aim of the review was to focus on the bioactive compounds and pharmacological properties of goji berries including their molecular mechanisms of action. The health benefits of goji berries include enhancing hemopoiesis, antiradiation, antiaging, anticancer, improvement of immunity, and antioxidation. There is a better protection through synergistic and additive effects in fruits and herbal products from a complex mixture of phytochemicals when compared to one single phytochemical.
Topics: Antioxidants; Fruit; Humans; Lycium
PubMed: 30728882
DOI: 10.1155/2019/2437397 -
Cells Mar 2023Vitiligo is an autoimmune skin disorder caused by dysfunctional pigment-producing melanocytes which are attacked by immune cells. Oxidative stress is considered to play... (Review)
Review
Vitiligo is an autoimmune skin disorder caused by dysfunctional pigment-producing melanocytes which are attacked by immune cells. Oxidative stress is considered to play a crucial role in activating consequent autoimmune responses related to vitiligo. Melanin synthesis by melanocytes is the main intracellular stressor, producing reactive oxygen species (ROS). Under normal physiological conditions, the antioxidative nuclear factor erythroid 2-related factor 2 (Nrf2) pathway functions as a crucial mediator for cells to resist oxidative stress. In pathological situations, such as with antioxidant defects or under inflammation, ROS accumulate and cause cell damage. Herein, we summarize events at the cellular level under excessive ROS in vitiligo and highlight exposure to melanocyte-specific antigens that trigger immune responses. Such responses lead to functional impairment and the death of melanocytes, which sequentially increase melanocyte cytotoxicity through both innate and adaptive immunity. This report provides new perspectives and advances our understanding of interrelationships between oxidative stress and autoimmunity in the pathogenesis of vitiligo. We describe progress with targeted antioxidant therapy, with the aim of providing potential therapeutic approaches.
Topics: Humans; Vitiligo; Antioxidants; Reactive Oxygen Species; Oxidative Stress; Hypopigmentation
PubMed: 36980277
DOI: 10.3390/cells12060936 -
Oxidative Medicine and Cellular... 2013Free radical damage is linked to formation of many degenerative diseases, including cancer, cardiovascular disease, cataracts, and aging. Excessive reactive oxygen... (Review)
Review
Free radical damage is linked to formation of many degenerative diseases, including cancer, cardiovascular disease, cataracts, and aging. Excessive reactive oxygen species (ROS) formation can induce oxidative stress, leading to cell damage that can culminate in cell death. Therefore, cells have antioxidant networks to scavenge excessively produced ROS. The balance between the production and scavenging of ROS leads to homeostasis in general; however, the balance is somehow shifted towards the formation of free radicals, which results in accumulated cell damage in time. Antioxidants can attenuate the damaging effects of ROS in vitro and delay many events that contribute to cellular aging. The use of multivitamin/mineral supplements (MVMs) has grown rapidly over the past decades. Some recent studies demonstrated no effect of antioxidant therapy; sometimes the intake of antioxidants even increased mortality. Oxidative stress is damaging and beneficial for the organism, as some ROS are signaling molecules in cellular signaling pathways. Lowering the levels of oxidative stress by antioxidant supplements is not beneficial in such cases. The balance between ROS and antioxidants is optimal, as both extremes, oxidative and antioxidative stress, are damaging. Therefore, there is a need for accurate determination of individual's oxidative stress levels before prescribing the supplement antioxidants.
Topics: Animals; Antioxidants; Humans; Models, Biological; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Signal Transduction
PubMed: 23738047
DOI: 10.1155/2013/956792 -
Redox Biology May 2021Recently, numerous evidence has revealed that excessive reactive oxygen species (ROS) production and mitochondrial disruption during acute lung injury (ALI) and its most...
Recently, numerous evidence has revealed that excessive reactive oxygen species (ROS) production and mitochondrial disruption during acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS) will aggravate the inflammatory process. To identify whether antioxidation can be one of the treatment strategies during this progress, we chose mitoQ, a mitochondria-targeted antioxidant that was proved to be effective in reducing ROS generated in mitochondria, as a ROS scavenger to investigate the role of antioxidation in ALI. We demonstrated that overoxidation occurred during the process of ALI, which could be reduced by mitoQ. In the meantime, apoptosis of endothelial cells of ALI mice, accompanied by hyperpermeability of pulmonary vascular and impaired pulmonary function, was partially reversed following an intraperitoneal injection of mitoQ. Moreover, in in vitro study, lipopolysaccharides (LPS) induced excessive ROS production, mitochondrial dysfunction and apoptosis in human pulmonary microvascular endothelial cells (HPMECs), which were rectified by mitoQ. To explore underlying mechanisms, we proceeded RNA-sequencing and found significantly upregulated expression of musculoaponeurotic fibrosarcoma F (MafF) in mitoQ treated group. Additionally, mitoQ inhibited the degradation and increased nuclear translocation of NF-E2-related factor 2 (Nrf2) and upregulated its downstream antioxidant response elements (AREs), such as heme oxygenase (HO)-1 and NAD(P)H:quinone oxidoreductase (NQO)-1. This effect was abolished by transfecting HPMECs with Nrf2 or Maff siRNA. In Nrf2 deficient mice, the protective effects of mitoQ on LPS model of ALI were largely vanished. Taken together, these results provide insights into how antioxidation exerts beneficial effects on ALI via maintaining mitochondrial hemostasis, inhibiting endothelial cells apoptosis, attenuating the endothelial disruption and regulating lung inflammation via Nrf2-MafF/ARE pathway.
Topics: Acute Lung Injury; Animals; Antioxidants; Endothelial Cells; Endothelium; Lipopolysaccharides; Mice; NF-E2-Related Factor 2; Signal Transduction
PubMed: 33752110
DOI: 10.1016/j.redox.2021.101936 -
Phytochemistry Jul 2015Carnosic acid (salvin), which possesses antioxidative and antimicrobial properties, is increasingly exploited within the food, nutritional health and cosmetics...
Carnosic acid (salvin), which possesses antioxidative and antimicrobial properties, is increasingly exploited within the food, nutritional health and cosmetics industries. Since its first extraction from a Salvia species (∼70 years ago) and its identification (∼50 years ago), numerous articles and patents (∼400) have been published on specific food and medicinal applications of Rosmarinus and Salvia plant extracts abundant in carnosic acid. In contrast, relevant biochemical, physiological or molecular studies in planta have remained rare. In this overview, recent advances in understanding of carnosic acid distribution, biosynthesis, accumulation and role in planta, and its applications are summarised. We also discuss the deficiencies in our understanding of the relevant biochemical processes, and suggest the molecular targets of carnosic acid. Finally, future perspectives and studies related to its potential roles are highlighted.
Topics: Abietanes; Animals; Anti-Infective Agents; Antioxidants; Chromatography, High Pressure Liquid; Humans; Mice; Molecular Structure; Plant Leaves; Rats; Rosmarinus; Salvia; Sheep
PubMed: 25639596
DOI: 10.1016/j.phytochem.2014.12.026 -
Neuron Oct 2022For many cancer patients, chemotherapy produces untreatable life-long neurologic effects termed chemotherapy-related cognitive impairment (CRCI). We discovered that the...
For many cancer patients, chemotherapy produces untreatable life-long neurologic effects termed chemotherapy-related cognitive impairment (CRCI). We discovered that the chemotherapy methotrexate (MTX) adversely affects oxidative metabolism of non-cancerous choroid plexus (ChP) cells and the cerebrospinal fluid (CSF). We used a ChP-targeted adeno-associated viral (AAV) vector approach in mice to augment CSF levels of the secreted antioxidant SOD3. AAV-SOD3 gene therapy increased oxidative defense capacity of the CSF and prevented MTX-induced lipid peroxidation in the hippocampus. Furthermore, this gene therapy prevented anxiety and deficits in short-term learning and memory caused by MTX. MTX-induced oxidative damage to cultured human cortical neurons and analyses of CSF samples from MTX-treated lymphoma patients demonstrated that MTX diminishes antioxidant capacity of patient CSF. Collectively, our findings motivate the advancement of ChP- and CSF-targeted anti-oxidative prophylactic measures to relieve CRCI.
Topics: Humans; Animals; Mice; Antioxidants; Choroid Plexus; Methotrexate; Oxidative Stress; Hippocampus; Neoplasms
PubMed: 36070751
DOI: 10.1016/j.neuron.2022.08.009 -
Journal of Nutritional Science and... 2022In the history of modern nutritional science, understanding antioxidants is one of the major topics. In many cases, food-derived antioxidants have π conjugate or thiol... (Review)
Review
In the history of modern nutritional science, understanding antioxidants is one of the major topics. In many cases, food-derived antioxidants have π conjugate or thiol group in their molecular structures because π conjugate stabilizes radical by its delocalization and two thiol groups form a disulfide bond in its antioxidative process. In recent years, antioxidant peptides have received much attention because for their ability to scavenge free radicals, inhibition of lipid peroxidation, chelation of transition metal ions, as well as their additional nutritional value. Among them, dipeptides are attracting much interest as post-amino acids, which have residues in common with amino acids, but also have different physiological properties and functions from those of amino acids. Especially, dipeptides containing moieties of several amino acid (tryptophan, tyrosine, histidine, cysteine, and methionine) possess potent antioxidant activity. This review summarizes previous details of structural property, radical scavenging activity, and biological activity of antioxidant dipeptide. Hopefully, this review will help provide a new insight into the study of the biological functions of antioxidant dipeptides.
Topics: Amino Acids; Antioxidants; Dipeptides; Food Additives; Lipid Peroxidation; Sulfhydryl Compounds
PubMed: 35768247
DOI: 10.3177/jnsv.68.162 -
International Journal of Molecular... Oct 2022Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as , , etc. Free radicals lead to the development of... (Review)
Review
Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as , , etc. Free radicals lead to the development of oxidative stress causing inflammation, arthritis, cancer, diabetes, fatty liver disease, etc. These further reduce the efficacy of anticancer drugs, activate inflammatory signaling pathways, degrade joints and cartilage, and disrupt the glycemic index and normal function of liver enzymes. For instance, the current treatment modalities used in arthritis such as non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatoid drugs, and lipoxygenase inhibitors present limited efficacy and adverse effects. Thus, there is a constant need to find newer and safer alternatives. Esculetin has an immense antioxidative potential thereby alleviating arthritis, diabetes, malignancies, and hepatic disorders. Structurally, esculetin contains two hydroxyl groups, which enhance its ability to function as an antioxidant by inhibiting oxidative stress in pathological conditions. Leukotriene B4 synthesis, NF-κB and MPAK pathway activation, and inflammatory cytokine production are the main causes of bone and joint deterioration in arthritis, whereas esculetin treatment reverses these factors and relieves the disease condition. In contrast, lipid peroxidation caused by upregulation of TGF-β-mediated expression and dysfunction of antioxidant enzymes is inhibited by esculetin therapy, thus reducing liver fibrosis by acting on the PI3K/FoxO1 pathway. Therefore, targeting NF-κB, pro-inflammatory cytokines, TGF-β and oxidative stress may be a therapeutic strategy to alleviate arthritis and liver fibrosis.
Topics: Humans; Antioxidants; NF-kappa B; Lipoxygenase Inhibitors; Leukotriene B4; Umbelliferones; Liver Cirrhosis; Cytokines; Anti-Inflammatory Agents; Phosphatidylinositol 3-Kinases; Antineoplastic Agents; Arthritis; Transforming Growth Factor beta
PubMed: 36293500
DOI: 10.3390/ijms232012643 -
Theranostics 2020Liver is the principal detoxifying organ and metabolizes various compounds that produce free radicals (FR) constantly. To maintain the oxidative/antioxidative balance in... (Review)
Review
Liver is the principal detoxifying organ and metabolizes various compounds that produce free radicals (FR) constantly. To maintain the oxidative/antioxidative balance in the liver, antioxidants would scavenge FR by preventing tissue damage through FR formation, scavenging, or by enhancing their decomposition. The disruption of this balance therefore leads to oxidative stress and in turn leads to the onset of various diseases. Supplying the liver with exogeneous antioxidants is an effective way to recreate the oxidative/antioxidative balance in the liver homeostasis. Nevertheless, due to the short half-life and instability of antioxidants in circulation, the methodology for delivering antioxidants to the liver needs to be improved. Nanocarrier mediated delivery of antioxidants proved to be an ingenious way to safely and efficiently deliver a high payload of antioxidants into the liver for circumventing liver diseases. The objective of this review is to provide an overview of the role of reactive oxygen species (oxidant) and ROS scavengers (antioxidant) in liver diseases. Subsequently, current nanocarrier mediated antioxidant delivery methods for liver diseases are discussed.
Topics: Animals; Antioxidants; Drug Carriers; Humans; Liver; Liver Diseases; Nanoparticles; Oxidative Stress; Reactive Oxygen Species
PubMed: 31938064
DOI: 10.7150/thno.38834