Cellular systems responsible for the formation and removal of reactive oxygen species (ROS), functioning within physiological limits, are essential for maintaining intracellular redox balance. This state is known as oxidative eustress. Key redox signaling molecules, such as superoxide anion radical (O2•-) and hydrogen peroxide (H2O2), operate at nanomolar concentrations and are produced by NADPH oxidases (regulated by various factors), the mitochondrial electron transport chain (ETC), and numerous enzymes. In addition, cell signaling is influenced by nitric oxide (NO•) and reactive lipid species. Disruption of ROS signaling can lead to oxidative stress, a harmful condition associated with many chronic diseases, including cancer. The dual nature of ROS is evident in premalignant and malignant cells at all stages of tumor development, including proliferation, migration/invasion, angiogenesis, inflammation, immune evasion, and metastasis. ROS can promote tumor formation by regulating immune cells, mitochondrial metabolism, DNA methylation, DNA damage [such as the DNA oxidation product, 8-oxo-dG, resulting from hydroxyl radical (•OH) attack], and other mechanisms. The tumor-promoting activity mediated by H2O2 manifests through the promotion of epithelial-to-mesenchymal transition (EMT) and the formation of the tumor microenvironment (TME) by tumor-associated macrophages. While ROS are vital for tumor initiation and growth, their excessive production can also have anticancer effects by inducing senescence, apoptosis, or necrosis. ROS-related anticancer mechanisms include mitochondrial dysfunction, p53-dependent apoptosis, iron-dependent ferroptosis, activation of endoplasmic reticulum stress, inhibition of growth signaling pathways (such as the epidermal growth factor pathway, EGF), among others. Tumor cells employ a range of adaptive mechanisms to effectively maintain ROS levels within a dynamic range that promotes proliferation while preventing cell death. This regulation is achieved by fine-tuning the effects of antioxidants throughout all stages of cancer. During early tumor development, characterized by increased oncogene-induced oxidative stress, cancer cells depend on glutathione (GSH) and upregulated antioxidant gene expression controlled by nuclear factor erythroid 2-related factor 2 (NRF2) to maintain redox balance. The opposing roles of certain antioxidant enzymes, such as Mn-SOD (SOD2), illustrate the same duality as ROS, acting as potential tumor suppressors during early carcinogenesis and as tumor promoters during metastasis. Low-molecular-weight antioxidants such as vitamins C (ascorbate) and E (tocopherols), carotenoids (e.g., lycopene, β-carotene), flavonoids (e.g., quercetin), and isoflavones demonstrate effective antioxidant activity in vitro, but their anticancer effects in clinical settings remain unproven. Understanding the influence of the antioxidant network and the redox threshold on epithelial-to-mesenchymal transition and key tumor microenvironment components could lead to more effective therapeutic strategies. This review explores the dual roles of ROS and antioxidants throughout different stages of cancer progression.

• Klíčová slova
• Antioxidants, Cancer, Cell signaling, Oxidative stress, ROS, Tumorigenesis,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Given the key importance played by the redox-active metals iron (Fe), copper (Cu), and manganese (Mn) in vital cellular processes, such as DNA synthesis, oxidative phosphorylation, the detoxification of reactive oxygen species (ROS), and angiogenesis, it is not surprising that their dysregulation plays a causative role in many human diseases. The same applies to redox-inactive zinc (Zn), which is involved in numerous biological functions, and serves as a structural element, a catalyst, and a participant in both intracellular and intercellular signaling and in maintaining immune system function. An imbalance in redox active (Fe, Cu, Mn) or redox inactive (Zn) metal ions, whether in excess or deficiency, is harmful and may disrupt the structural, regulatory, and catalytic roles of various antioxidant enzymes (superoxide dismutases (SODs), catalase (CAT), glutathione peroxidases (GPxs)), proteins, receptors, transporters, alter sulfhydryl homeostasis, generate high levels of ROS (e.g., hydroxyl radicals by the Fenton reaction), initiate lipid peroxidation, cause DNA damage, and lead to cell death via mechanisms such as ferroptosis, cuproptosis, cellular senescence, or inflammation. Maintaining redox homeostasis is essential for regulating numerous cellular signaling pathways. Redox-sensitive signaling pathways, such as the nuclear factor kappa B (NF-κB), mitogen-activated protein kinase kinase (MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, form an intricate network that governs cellular responses to redox metal-induced oxidative stress and inflammation. The Nrf2 pathway is primarily responsible for mediating antioxidant defenses, whereas the NF-κB and MAPK pathways play roles in proinflammatory and stress-related responses. Dysregulation of redox-active Fe, Cu, Mn, and redox-inactive Zn can alter epigenetic regulatory mechanisms such as DNA methylation, histone modification, and non-coding RNA expression. The dyshomeostasis of metal ions is closely related to the pathogenesis of lung, renal, and gastrointestinal diseases, neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, and Huntington's disease), psychiatric conditions (schizophrenia), and various cancers. This review summarizes recent findings on the role of iron, copper, manganese, and zinc in maintaining physiological functions, redox homeostasis, and human diseases. See also the graphical abstract(Fig. 1).

• Klíčová slova
• copper, human diseases, iron, manganese, oxidative stress, zinc,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Myocardial infarction is a leading cause of death and morbidity in individuals with cardiovascular diseases. Natural antioxidants, such as those found in green tea leaves, are beneficial in preventing these diseases. This study evaluated the protective effects of green tea leaves powder against isoprenaline (ISO)-induced myocardial infarction in rats. Four groups of male Long Evans rats were used: Control, Control + green tea leaves powder, ISO, and ISO + green tea leaves powder. Organ and blood plasma samples were collected to measure oxidative stress biomarkers, biochemical parameters, and gene expressions. Furthermore, tissue sections were prepared and stained histologically. ISO-induced rats showed decreased cellular antioxidants (catalase activity and glutathione concentration) and elevated oxidative stress markers. Notable inflammatory cell infiltration and fibrosis were observed in the heart and kidneys of ISO-induced rats. Supplementation with green tea leaves powder significantly restored catalase activity and glutathione concentration (p < 0.05) in plasma and tissues. It also considerably reduced lipid peroxidation, nitric oxide, and advanced oxidation protein products (p < 0.05) in ISO-administered rats. Furthermore, green tea leaves powder supplementation halted inflammatory gene expression (p < 0.05), restored antioxidant genes (p < 0.05) such as Nrf-2-HO-1, and prevented cardiac fibrosis in ISO-administered rats. Green tea leaves powder supplementation may reduce oxidative stress, inflammation, and fibrosis in ISO-administered rats, potentially through the Nrf-2-HO-1-mediated restoration of antioxidant enzymes and prevention of heart inflammation.

• Klíčová slova
• Camellia sinensis, Fibrosis, Inflammation, Isoprenaline, Myocardial infarction,
• MeSH
• antioxidancia * metabolismus   farmakologie   MeSH
• čajovník čínský * chemie   MeSH
• faktor 2 související s NF-E2 * metabolismus   MeSH
• hemová oxygenasa (decyklizující) MeSH
• infarkt myokardu * chemicky indukované   farmakoterapie   metabolismus   patologie   MeSH
• isoprenalin škodlivé účinky   MeSH
• katechin * farmakologie   MeSH
• krysa rodu Rattus MeSH
• myokard patologie   metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• polyfenoly * farmakologie   chemie   MeSH
• poranění srdce * chemicky indukované   farmakoterapie   metabolismus   MeSH
• potkani Long-Evans MeSH
• prášky, zásypy, pudry MeSH
• rostlinné extrakty farmakologie   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia * MeSH
• faktor 2 související s NF-E2 * MeSH
• hemová oxygenasa (decyklizující) MeSH
• Hmox1 protein, rat MeSH Prohlížeč
• isoprenalin MeSH
• katechin * MeSH
• Nfe2l2 protein, rat MeSH Prohlížeč
• polyfenoly * MeSH
• prášky, zásypy, pudry MeSH
• rostlinné extrakty MeSH

Heavy metals are naturally occurring components of the Earth's crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·-), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO-). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.

• Klíčová slova
• Antioxidant enzymes, Heavy metals, Human disease, Oxidative stress, ROS, Toxicity,
• MeSH
• antioxidancia metabolismus   MeSH
• látky znečišťující životní prostředí * toxicita   farmakokinetika   MeSH
• lidé MeSH
• otrava těžkými kovy MeSH
• oxidační stres účinky léků   MeSH
• těžké kovy * toxicita   farmakokinetika   MeSH
• vystavení vlivu životního prostředí * škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia MeSH
• látky znečišťující životní prostředí * MeSH
• těžké kovy * MeSH

A laser-plasma source emitting photons with energies in the water window spectral range has been used to reveal the radiation chemical yields of single-strand breaks in plasmid DNA as a function of ·OH radical scavenger concentration. Direct and indirect effects were investigated separately using DNA samples with various levels of hydration. We experimentally determined the value of the efficiency factor for strand cleavage in DNA caused by the reaction with ·OH radicals at 0.11, which was previously found in the theoretical studies. Additionally, the radiation chemical yield of ·OH radicals specific to the water window radiation emission of the source was determined by comparison with the gamma radiation-induced strand break yields. The ·OH radical yield determined using the plasmid DNA samples as a model was similar to the yield found using sensitive fluorescent dosimeters in previous experiments.

• Klíčová slova
• Gamma radiation, OH radical, Plasmid DNA, Radical scavengers, Soft X-rays,
• MeSH
• DNA * chemie   MeSH
• hydroxylový radikál * chemie   MeSH
• jednořetězcové zlomy DNA MeSH
• plazmidy chemie   MeSH
• rentgenové záření MeSH
• scavengery volných radikálů chemie   MeSH
• voda * chemie   MeSH
• záření gama MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA * MeSH
• hydroxylový radikál * MeSH
• scavengery volných radikálů MeSH
• voda * MeSH

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system. The first-line defense mechanism is the most efficient and involves antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This line of defense plays an irreplaceable role in the dismutation of superoxide radicals (O2•-) and hydrogen peroxide (H2O2). The removal of superoxide radicals by SOD prevents the formation of the much more damaging peroxynitrite ONOO- (O2•- + NO• → ONOO-) and maintains the physiologically relevant level of nitric oxide (NO•), an important molecule in neurotransmission, inflammation, and vasodilation. The second-line antioxidant defense pathway involves exogenous diet-derived small-molecule antioxidants. The third-line antioxidant defense is ensured by the repair or removal of oxidized proteins and other biomolecules by a variety of enzyme systems. This review briefly discusses the endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) and exogenous (e.g., smoking, radiation, drugs, pollution) sources of ROS (superoxide radical, hydrogen peroxide, hydroxyl radical, peroxyl radical, hypochlorous acid, peroxynitrite). Attention has been given to the first-line antioxidant defense system provided by SOD, CAT, and GPx. The chemical and molecular mechanisms of antioxidant enzymes, enzyme-related diseases (cancer, cardiovascular, lung, metabolic, and neurological diseases), and the role of enzymes (e.g., GPx4) in cellular processes such as ferroptosis are discussed. Potential therapeutic applications of enzyme mimics and recent progress in metal-based (copper, iron, cobalt, molybdenum, cerium) and nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) are also discussed. Moreover, attention has been given to the mechanisms of action of low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids (e.g., β-carotene, lycopene, lutein), flavonoids (e.g., quercetin, anthocyanins, epicatechin), and glutathione (GSH)), the activation of transcription factors such as Nrf2, and the protection against chronic diseases. Given that there is a discrepancy between preclinical and clinical studies, approaches that may result in greater pharmacological and clinical success of low-molecular-weight antioxidant therapies are also subject to discussion.

• Klíčová slova
• Antioxidant enzymes, Chronic disease, Enzyme mimics, Low-molecular antioxidants, Oxidative stress, ROS,
• MeSH
• anthokyaniny metabolismus   farmakologie   MeSH
• antioxidancia * farmakologie   metabolismus   MeSH
• chronická nemoc MeSH
• kyselina peroxydusitá farmakologie   MeSH
• lidé MeSH
• nádory * MeSH
• oxid dusnatý MeSH
• oxidační stres MeSH
• peroxid vodíku MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• superoxiddismutasa metabolismus   MeSH
• superoxidy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• anthokyaniny MeSH
• antioxidancia * MeSH
• kyselina peroxydusitá MeSH
• oxid dusnatý MeSH
• peroxid vodíku MeSH
• reaktivní formy kyslíku MeSH
• superoxiddismutasa MeSH
• superoxidy MeSH