Editorial

7 pages, 1121 KiB

Open AccessEditorial

Biomarkers of Oxidative and Radical Stress

by Chryssostomos Chatgilialoglu

Biomolecules 2024, 14(2), 194; https://doi.org/10.3390/biom14020194 - 05 Feb 2024

Viewed by 847

Reactive oxygen and nitrogen species (ROS/RNS) are generated as a result of normal intracellular metabolism [...] Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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Research

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18 pages, 5668 KiB

Open AccessArticle

Melatonin as a Repairing Agent in Cadmium- and Free Fatty Acid-Induced Lipotoxicity

by Anna Migni, Francesca Mancuso, Tiziano Baroni, Gabriele Di Sante, Mario Rende, Francesco Galli and Desirée Bartolini

Biomolecules 2023, 13(12), 1758; https://doi.org/10.3390/biom13121758 - 07 Dec 2023

Cited by 1 | Viewed by 899

Abstract

(1) Background: Cadmium (Cd) is a potentially toxic element with a long half-life in the human body (20–40 years). Cytotoxicity mechanisms of Cd include increased levels of oxidative stress and apoptotic signaling, and recent studies have suggested that these aspects of Cd toxicity [...] Read more.

(1) Background: Cadmium (Cd) is a potentially toxic element with a long half-life in the human body (20–40 years). Cytotoxicity mechanisms of Cd include increased levels of oxidative stress and apoptotic signaling, and recent studies have suggested that these aspects of Cd toxicity contribute a role in the pathobiology of non-alcoholic fatty liver disease (NAFLD), a highly prevalent ailment associated with hepatic lipotoxicity and an increased generation of reactive oxygen species (ROS). In this study, Cd toxicity and its interplay with fatty acid (FA)-induced lipotoxicity have been studied in intestinal epithelium and liver cells; the cytoprotective function of melatonin (MLT) has been also evaluated. (2) Methods: human liver cells (HepaRG), primary murine hepatocytes and Caco-2 intestinal epithelial cells were exposed to CdCl₂ before and after induction of lipotoxicity with oleic acid (OA) and/or palmitic acid (PA), and in some experiments, FA was combined with MLT (50 nM) treatment. (3) Results: CdCl₂ toxicity was associated with ROS induction and reduced cell viability in both the hepatic and intestinal cells. Cd and FA synergized to induce lipid droplet formation and ROS production; the latter was higher for PA compared to OA in liver cells, resulting in a higher reduction in cell viability, especially in HepaRG and primary hepatocytes, whereas CACO-2 cells showed higher resistance to Cd/PA-induced lipotoxicity compared to liver cells. MLT showed significant protection against Cd toxicity either considered alone or combined with FFA-induced lipotoxicity in primary liver cells. (4) Conclusions: Cd and PA combine their pro-oxidant activity to induce lipotoxicity in cellular populations of the gut–liver axis. MLT can be used to lessen the synergistic effect of Cd-PA on cellular ROS formation. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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17 pages, 5074 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Physico-Chemical Changes Induced by Gamma Irradiation on Some Structural Protein Extracts

by Maria Stanca, Carmen Gaidau, Traian Zaharescu, George-Alin Balan, Iulia Matei, Aurica Precupas, Anca Ruxandra Leonties and Gabriela Ionita

Biomolecules 2023, 13(5), 774; https://doi.org/10.3390/biom13050774 - 29 Apr 2023

Cited by 4 | Viewed by 1447

Abstract

In this study, the effect of gamma irradiation (10 kGy) on proteins extracted from animal hide, scales, and wool was evidenced by calorimetric (μDSC) and spectroscopic (IR, circular dichroism, and EPR) methods. Keratin was obtained from sheep wool, collagen and bovine gelatin from [...] Read more.

In this study, the effect of gamma irradiation (10 kGy) on proteins extracted from animal hide, scales, and wool was evidenced by calorimetric (μDSC) and spectroscopic (IR, circular dichroism, and EPR) methods. Keratin was obtained from sheep wool, collagen and bovine gelatin from bovine hide, and fish gelatin from fish scales. The μDSC experiments evidenced that gamma irradiation influences the thermal stability of these proteins differently. The thermal stability of keratin decreases, while a resistance to thermal denaturation was noticed for collagen and gelatins after gamma irradiation. The analysis of the IR spectra demonstrated that gamma irradiation determines changes in the vibrational modes of the amide groups that are associated with protein denaturation, most meaningfully in the case of keratin. As evidenced by circular dichroism for all proteins considered, exposure to gamma radiation produces changes in the secondary structure that are more significant than those produced by UV irradiation. Riboflavin has different effects on the secondary structure of the investigated proteins, a stabilizing effect for keratin and fish gelatin and a destabilizing effect for bovine gelatin, observed in both irradiated and non-irradiated samples. The EPR spectroscopy evidences the presence, in the gamma-irradiated samples, of free radicals centered on oxygen, and the increase in their EPR signals over time due to the presence of riboflavin. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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17 pages, 2389 KiB

Open AccessEditor’s ChoiceArticle

Plasmalogens: Free Radical Reactivity and Identification of Trans Isomers Relevant to Biological Membranes

by Carla Ferreri, Alessandra Ferocino, Gessica Batani, Chryssostomos Chatgilialoglu, Vanda Randi, Maria Vittoria Riontino, Fabrizio Vetica and Anna Sansone

Biomolecules 2023, 13(5), 730; https://doi.org/10.3390/biom13050730 - 24 Apr 2023

Cited by 4 | Viewed by 2260

Abstract

Plasmalogens are membrane phospholipids with two fatty acid hydrocarbon chains linked to L-glycerol, one containing a characteristic cis-vinyl ether function and the other one being a polyunsaturated fatty acid (PUFA) residue linked through an acyl function. All double bonds in these structures display [...] Read more.

Plasmalogens are membrane phospholipids with two fatty acid hydrocarbon chains linked to L-glycerol, one containing a characteristic cis-vinyl ether function and the other one being a polyunsaturated fatty acid (PUFA) residue linked through an acyl function. All double bonds in these structures display the cis geometrical configuration due to desaturase enzymatic activity and they are known to be involved in the peroxidation process, whereas the reactivity through cis-trans double bond isomerization has not yet been identified. Using 1-(1Z-octadecenyl)-2-arachidonoyl-sn-glycero-3-phosphocholine (C18 plasm-20:4 PC) as a representative molecule, we showed that the cis-trans isomerization can occur at both plasmalogen unsaturated moieties, and the product has characteristic analytical signatures useful for omics applications. Using plasmalogen-containing liposomes and red blood cell (RBC) ghosts under biomimetic Fenton-like conditions, in the presence or absence of thiols, peroxidation, and isomerization processes were found to occur with different reaction outcomes due to the particular liposome compositions. These results allow gaining a full scenario of plasmalogen reactivity under free radical conditions. Moreover, clarification of the plasmalogen reactivity under acidic and alkaline conditions was carried out, identifying the best protocol for RBC membrane fatty acid analysis due to their plasmalogen content of 15–20%. These results are important for lipidomic applications and for achieving a full scenario of radical stress in living organisms. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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22 pages, 11271 KiB

Open AccessFeature PaperArticle

Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer

by Matea Nikolac Perkovic, Morana Jaganjac, Lidija Milkovic, Tea Horvat, David Rojo, Kamelija Zarkovic, Marijana Ćorić, Tvrtko Hudolin, Georg Waeg, Biserka Orehovec and Neven Zarkovic

Biomolecules 2023, 13(1), 145; https://doi.org/10.3390/biom13010145 - 10 Jan 2023

Cited by 9 | Viewed by 2826

Abstract

An oxidative degradation product of the polyunsaturated fatty acids, 4-hydroxynonenal (4-HNE), is of particular interest in cancer research due to its concentration-dependent pleiotropic activities affecting cellular antioxidants, metabolism, and growth control. Although an increase in oxidative stress and lipid peroxidation was already associated [...] Read more.

An oxidative degradation product of the polyunsaturated fatty acids, 4-hydroxynonenal (4-HNE), is of particular interest in cancer research due to its concentration-dependent pleiotropic activities affecting cellular antioxidants, metabolism, and growth control. Although an increase in oxidative stress and lipid peroxidation was already associated with prostate cancer progression a few decades ago, the knowledge of the involvement of 4-HNE in prostate cancer tumorigenesis is limited. This study investigated the appearance of 4-HNE-protein adducts in prostate cancer tissue by immunohistochemistry using a genuine 4-HNE monoclonal antibody. Plasma samples of the same patients and samples of the healthy controls were also analyzed for the presence of 4-HNE-protein adducts, followed by metabolic profiling using LC-ESI-QTOF-MS and GC-EI-Q-MS. Finally, the analysis of the metabolic pathways affected by 4-HNE was performed. The obtained results revealed the absence of 4-HNE-protein adducts in prostate carcinoma tissue but increased 4-HNE-protein levels in the plasma of these patients. Metabolomics revealed a positive association of different long-chain and medium-chain fatty acids with the presence of prostate cancer. Furthermore, while linoleic acid positively correlated with the levels of 4-HNE-protein adducts in the blood of healthy men, no correlation was obtained for cancer patients indicating altered lipid metabolism in this case. The metabolic pathway of unsaturated fatty acids biosynthesis emerged as significantly affected by 4-HNE. Overall, this is the first study linking 4-HNE adduction to plasma proteins with specific alterations in the plasma metabolome of prostate cancer patients. This study revealed that increased 4-HNE plasma protein adducts could modulate the unsaturated fatty acids biosynthesis pathway. It is yet to be determined if this is a direct result of 4-HNE or whether they are produced by the same underlying mechanisms. Further mechanistic studies are needed to grasp the biological significance of the observed changes in prostate cancer tumorigenesis. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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14 pages, 3929 KiB

Open AccessArticle

Assessing the Formation of Purine Lesions in Mitochondrial DNA of Cockayne Syndrome Cells

by Chryssostomos Chatgilialoglu, Marios G. Krokidis, Annalisa Masi, Sebastian Barata-Vallejo, Carla Ferreri, Barbara Pascucci and Mariarosaria D’Errico

Biomolecules 2022, 12(11), 1630; https://doi.org/10.3390/biom12111630 - 03 Nov 2022

Cited by 3 | Viewed by 1523

Abstract

Mitochondrial (mt) DNA and nuclear (n) DNA have known structures and roles in cells; however, they are rarely compared under specific conditions such as oxidative or degenerative environments that can create damage to the DNA base moieties. Six purine lesions were ascertained in [...] Read more.

Mitochondrial (mt) DNA and nuclear (n) DNA have known structures and roles in cells; however, they are rarely compared under specific conditions such as oxidative or degenerative environments that can create damage to the DNA base moieties. Six purine lesions were ascertained in the mtDNA of wild type (wt) CSA (CS3BE–wtCSA) and wtCSB (CS1AN–wtCSB) cells and defective counterparts CS3BE and CS1AN in comparison with the corresponding total (t) DNA (t = n + mt). In particular, the four 5′,8–cyclopurine (cPu) and the two 8–oxo–purine (8–oxo–Pu) lesions were accurately quantified by LC–MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. The 8–oxo–Pu levels were found to be in the range of 25–50 lesions/10⁷ nucleotides in both the mtDNA and tDNA. The four cPu were undetectable in the mtDNA both in defective cells and in the wt counterparts (CSA and CSB), contrary to their detection in tDNA, indicating a nonappearance of hydroxyl radical (HO^•) reactivity within the mtDNA. In order to assess the HO^• reactivity towards purine nucleobases in the two genetic materials, we performed γ–radiolysis experiments coupled with the 8–oxo–Pu and cPu quantifications on isolated mtDNA and tDNA from wtCSB cells. In the latter experiments, all six purine lesions were detected in both of the DNA, showing a higher resistance to HO^• attack in the case of mtDNA compared with tDNA, likely due to their different DNA helical topology influencing the relative abundance of the lesions. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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18 pages, 2227 KiB

Open AccessArticle

Effects of Aging and Disease Conditions in Brain of Tumor-Bearing Mice: Evaluation of Purine DNA Damages and Fatty Acid Pool Changes

by Marios G. Krokidis, Paraskevi Prasinou, Eleni K. Efthimiadou, Andrea Boari, Carla Ferreri and Chryssostomos Chatgilialoglu

Biomolecules 2022, 12(8), 1075; https://doi.org/10.3390/biom12081075 - 04 Aug 2022

Cited by 5 | Viewed by 2021

Abstract

The consequences of aging and disease conditions in tissues involve reactive oxygen species (ROS) and related molecular alterations of different cellular compartments. We compared a murine model of immunodeficient (SCID) xenografted young (4 weeks old) and old (17 weeks old) mice with corresponding [...] Read more.

The consequences of aging and disease conditions in tissues involve reactive oxygen species (ROS) and related molecular alterations of different cellular compartments. We compared a murine model of immunodeficient (SCID) xenografted young (4 weeks old) and old (17 weeks old) mice with corresponding controls without tumor implantation and carried out a compositional evaluation of brain tissue for changes in parallel DNA and lipids compartments. DNA damage was measured by four purine 5′,8-cyclo-2′-deoxynucleosides, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), and 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxo-dA). In brain lipids, the twelve most representative fatty acid levels, which were mostly obtained from the transformation of glycerophospholipids, were followed up during the aging and disease progressions. The progressive DNA damage due to age and tumoral conditions was confirmed by raised levels of 5′S-cdG and 5′S-cdA. In the brain, the remodeling involved a diminution of palmitic acid accompanied by an increase in arachidonic acid, along both age and tumor progressions, causing increases in the unsaturation index, the peroxidation index, and total TFA as indicators of increased oxidative and free radical reactivity. Our results contribute to the ongoing debate on the central role of DNA and genome instability in the aging process, and on the need for a holistic vision, which implies choosing the best biomarkers for such monitoring. Furthermore, our data highlight brain tissue for its lipid remodeling response and inflammatory signaling, which seem to prevail over the effects of DNA damage. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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Review

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30 pages, 3364 KiB

Open AccessEditor’s ChoiceReview

Impact of Polyphenols on Inflammatory and Oxidative Stress Factors in Diabetes Mellitus: Nutritional Antioxidants and Their Application in Improving Antidiabetic Therapy

by Michal Krawczyk, Izabela Burzynska-Pedziwiatr, Lucyna A. Wozniak and Malgorzata Bukowiecka-Matusiak

Biomolecules 2023, 13(9), 1402; https://doi.org/10.3390/biom13091402 - 17 Sep 2023

Cited by 6 | Viewed by 2519

Abstract

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia and oxidative stress. Oxidative stress plays a crucial role in the development and progression of diabetes and its complications. Nutritional antioxidants derived from dietary sources have gained significant attention due to their potential [...] Read more.

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia and oxidative stress. Oxidative stress plays a crucial role in the development and progression of diabetes and its complications. Nutritional antioxidants derived from dietary sources have gained significant attention due to their potential to improve antidiabetic therapy. This review will delve into the world of polyphenols, investigating their origins in plants, metabolism in the human body, and relevance to the antioxidant mechanism in the context of improving antidiabetic therapy by attenuating oxidative stress, improving insulin sensitivity, and preserving β-cell function. The potential mechanisms of, clinical evidence for, and future perspectives on nutritional antioxidants as adjuvant therapy in diabetes management are discussed. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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33 pages, 5052 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Lipid Peroxidation and Antioxidant Protection

by Luca Valgimigli

Biomolecules 2023, 13(9), 1291; https://doi.org/10.3390/biom13091291 - 24 Aug 2023

Cited by 5 | Viewed by 2295

Abstract

Lipid peroxidation (LP) is the most important type of oxidative-radical damage in biological systems, owing to its interplay with ferroptosis and to its role in secondary damage to other biomolecules, such as proteins. The chemistry of LP and its biological consequences are reviewed [...] Read more.

Lipid peroxidation (LP) is the most important type of oxidative-radical damage in biological systems, owing to its interplay with ferroptosis and to its role in secondary damage to other biomolecules, such as proteins. The chemistry of LP and its biological consequences are reviewed with focus on the kinetics of the various processes, which helps understand the mechanisms and efficacy of antioxidant strategies. The main types of antioxidants are discussed in terms of structure–activity rationalization, with focus on mechanism and kinetics, as well as on their potential role in modulating ferroptosis. Phenols, pyri(mi)dinols, antioxidants based on heavy chalcogens (Se and Te), diarylamines, ascorbate and others are addressed, along with the latest unconventional antioxidant strategies based on the double-sided role of the superoxide/hydroperoxyl radical system. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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20 pages, 1416 KiB

Open AccessReview

Oxidative Stress in Healthy and Pathological Red Blood Cells

by Florencia Orrico, Sandrine Laurance, Ana C. Lopez, Sophie D. Lefevre, Leonor Thomson, Matias N. Möller and Mariano A. Ostuni

Biomolecules 2023, 13(8), 1262; https://doi.org/10.3390/biom13081262 - 18 Aug 2023

Cited by 8 | Viewed by 3669

Abstract

Red cell diseases encompass a group of inherited or acquired erythrocyte disorders that affect the structure, function, or production of red blood cells (RBCs). These disorders can lead to various clinical manifestations, including anemia, hemolysis, inflammation, and impaired oxygen-carrying capacity. Oxidative stress, characterized [...] Read more.

Red cell diseases encompass a group of inherited or acquired erythrocyte disorders that affect the structure, function, or production of red blood cells (RBCs). These disorders can lead to various clinical manifestations, including anemia, hemolysis, inflammation, and impaired oxygen-carrying capacity. Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense mechanisms, plays a significant role in the pathophysiology of red cell diseases. In this review, we discuss the most relevant oxidant species involved in RBC damage, the enzymatic and low molecular weight antioxidant systems that protect RBCs against oxidative injury, and finally, the role of oxidative stress in different red cell diseases, including sickle cell disease, glucose 6-phosphate dehydrogenase deficiency, and pyruvate kinase deficiency, highlighting the underlying mechanisms leading to pathological RBC phenotypes. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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15 pages, 1721 KiB

Open AccessReview

Primary Processes of Free Radical Formation in Pharmaceutical Formulations of Therapeutic Proteins

by Christian Schöneich

Biomolecules 2023, 13(7), 1142; https://doi.org/10.3390/biom13071142 - 17 Jul 2023

Cited by 2 | Viewed by 1817

Abstract

Oxidation represents a major pathway for the chemical degradation of pharmaceutical formulations. Few specific details are available on the mechanisms that trigger oxidation reactions in these formulations, specifically with respect to the formation of free radicals. Hence, these mechanisms must be formulated based [...] Read more.

Oxidation represents a major pathway for the chemical degradation of pharmaceutical formulations. Few specific details are available on the mechanisms that trigger oxidation reactions in these formulations, specifically with respect to the formation of free radicals. Hence, these mechanisms must be formulated based on information on impurities and stress factors resulting from manufacturing, transportation and storage. In more detail, this article focusses on autoxidation, metal-catalyzed oxidation, photo-degradation and radicals generated from cavitation as a result of mechanical stress. Emphasis is placed on probable rather than theoretically possible pathways. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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15 pages, 568 KiB

Open AccessReview

Factors Important in the Use of Fluorescent or Luminescent Probes and Other Chemical Reagents to Measure Oxidative and Radical Stress

by Peter Wardman

Biomolecules 2023, 13(7), 1041; https://doi.org/10.3390/biom13071041 - 26 Jun 2023

Cited by 3 | Viewed by 1249

Abstract

Numerous chemical probes have been used to measure or image oxidative, nitrosative and related stress induced by free radicals in biology and biochemistry. In many instances, the chemical pathways involved are reasonably well understood. However, the rate constants for key reactions involved are [...] Read more.

Numerous chemical probes have been used to measure or image oxidative, nitrosative and related stress induced by free radicals in biology and biochemistry. In many instances, the chemical pathways involved are reasonably well understood. However, the rate constants for key reactions involved are often not yet characterized, and thus it is difficult to ensure the measurements reflect the flux of oxidant/radical species and are not influenced by competing factors. Key questions frequently unanswered are whether the reagents are used under ‘saturating’ conditions, how specific probes are for particular radicals or oxidants and the extent of the involvement of competing reactions (e.g., with thiols, ascorbate and other antioxidants). The commonest-used probe for ‘reactive oxygen species’ in biology actually generates superoxide radicals in producing the measured product in aerobic systems. This review emphasizes the need to understand reaction pathways and in particular to quantify the kinetic parameters of key reactions, as well as measure the intracellular levels and localization of probes, if such reagents are to be used with confidence. Full article

(This article belongs to the Special Issue Biomarkers of Oxidative and Radical Stress)

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