Special Issue "10th Anniversary of Antioxidants—Aberrant and Signaling Oxidation of Biomolecules"

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Aberrant Oxidation of Biomolecules".

Deadline for manuscript submissions: 30 September 2022 | Viewed by 3152

Special Issue Editors

Prof. Dr. Giancarlo Aldini
E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milan, Italy
Interests: reactive carbonyls species; advanced glycation end products (AGEs); advanced lipoxidation end products (ALEs); sequestering agents; protein adducts
Special Issues, Collections and Topics in MDPI journals
Dr. Alessandra Altomare
E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, University of Milan, Via Luigi Mangiagalli 25, 20133 Milan, Italy
Interests: liquid chromatography; reactive carbonyl species; spectrometry
Dr. Giovanna Baron
E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Università degli Studi di Milano, 20122 Milan, Italy
Interests: medicinal chemistry; lipid peroxidation; antioxidant activity

Special Issue Information

Dear Colleagues,

Biomolecule oxidation involves covalent modifications and occurs both by direct and indirect reaction mechanisms; the direct oxidation is mediated by reactive oxygen species (ROS), the indirect by secondary by-products of oxidative stress, such as lipid-peroxidation break-down products, which covalently adduct the biomolecules.

In vitro and in vivo evidence indicates that biomolecule oxidation is involved in the onset and propagation of several diseases, including cardiovascular and neurological disorders. The damaging effect can be mediated by several mechanisms, including a direct dysregulating effect of the target biomolecule, oligomerization, and epitope formation.

Most recently, it has been found that besides inducing a damaging effect, protein oxidation, in some circumstances, can exert a beneficial effect by stimulating the Nrf2-antioxidant response element signaling pathway; Nrf2 activation controls the expression of genes whose protein products enhance cellular antioxidant capacity and are involved in the detoxication and elimination of reactive oxidants and electrophilic agents.

Based on the above-mentioned premises, the aim of the Special Issue is to collect research and review papers focusing on the damaging and signaling processes induced by oxidized proteins. Papers on the following topics, among others, are welcome: methodological papers on cutting edge analytical approaches for the identification, characterization, and quantification of oxidized biomolecules in different biological samples, including plant, animal and human specimens; OMICs approaches (genomic, proteomic, metabolomic, and lipidomic) to investigate the effect of oxidized biomolecules on cellular pathways; in vitro and in vivo studies on cell signaling evoked by oxidized biomolecules; cellular mechanisms for degradation and removal of oxidized proteins and their regulation; and oxidized biomolecules as drug target and medicinal chemistry approaches for their regulation.

Prof. Dr. Giancarlo Aldini
Dr. Alessandra Altomare
Dr. Giovanna Baron
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (5 papers)

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Research

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Article
The Burden of Impaired Serum Albumin Antioxidant Properties and Glyco-Oxidation in Coronary Heart Disease Patients with and without Type 2 Diabetes Mellitus
Antioxidants 2022, 11(8), 1501; https://doi.org/10.3390/antiox11081501 - 30 Jul 2022
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Abstract
Human serum albumin (HSA) has an important antioxidant activity due to the presence of the reduced cysteine at position 34, which represents the most abundant free thiol in the plasma. In oxidative-based diseases, HSA undergoes S-thiolation (THIO-HSA) with changes in the antioxidant function [...] Read more.
Human serum albumin (HSA) has an important antioxidant activity due to the presence of the reduced cysteine at position 34, which represents the most abundant free thiol in the plasma. In oxidative-based diseases, HSA undergoes S-thiolation (THIO-HSA) with changes in the antioxidant function of albumin that could contribute to the progression of the disease. The aim of this study was to verify, for the first time, the different burdens of THIO-HSA, glycated HSA (GLY-HSA), and advanced glycation end products (AGE) accumulation both in type 2 diabetes mellitus (T2DM) patients and in non-diabetic patients, with or without coronary heart disease (CHD). In this study, we assessed the presence of modified forms of HSA, THIO-HSA, and GLY-HSA by means of mass spectrometry in 33 patients with both T2DM and CHD, in 31 patients with T2DM and without CHD, in 30 patients without diabetes with a history of CHD, and 27 subjects without diabetes and CHD. All the patients’ anthropometric and clinical data were recorded including age, sex, duration of diabetes, body mass index (BMI), blood pressure, and history of CHD defined with anamnestic data. Metabolic parameters, such as fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipids, pentosidine, AGE, receptor for advanced glycation end-products (RAGE) and its soluble form (sRAGE), were measured. AGE and pentosidine are significantly higher in T2DM patients with and without CHD with respect to non-diabetic patients with CHD and control subjects. RAGE levels are significantly higher in T2DM patients with respect to non-diabetic patients, and among T2DM patients, the group with CHD showed significantly higher RAGE levels than those without CHD (217 ± 171 pg/mL and 140 ± 61 pg/mL, respectively). Albumin isoforms discriminate between non-diabetic patients with CHD and T2DM patients with and without CHD and control subjects, with GLY-HSA levels higher in T2DM with and without CHD, and THIO-HSA higher in CHD patients without T2DM. Finally, we demonstrated that the oxidized forms of HSA can increase the expression of the inflammatory cytokine Tumor Necrosis Factor-alpha (TNFα) in monocytic cells. In patients with CHD, GLY-HSA and THIO-HSA have a different prevalent distribution, the first one prevailing in patients with T2DM and the second one in patients without T2DM. These findings suggest that albumin quality and homeostasis balance between glyco-oxidation and thiolation might have an impact on the antioxidant defense system in cardiovascular diseases. Full article
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Article
Doxorubicin Induces Bone Loss by Increasing Autophagy through a Mitochondrial ROS/TRPML1/TFEB Axis in Osteoclasts
Antioxidants 2022, 11(8), 1476; https://doi.org/10.3390/antiox11081476 - 28 Jul 2022
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Abstract
Doxorubicin (DOX), a widely used chemotherapeutic agent, has been linked to an increased risk of bone damage in human patients and induces bone loss in mice. DOX induces autophagy, which contributes to bone homeostasis and excess autophagy in osteoclasts (OCs), resulting in bone [...] Read more.
Doxorubicin (DOX), a widely used chemotherapeutic agent, has been linked to an increased risk of bone damage in human patients and induces bone loss in mice. DOX induces autophagy, which contributes to bone homeostasis and excess autophagy in osteoclasts (OCs), resulting in bone loss. We hypothesized that DOX-induced bone loss is caused by the induction of autophagy in OCs. In vitro, DOX significantly increased the area of OCs and bone resorption activity, whereas it decreased OC number through apoptosis. DOX enhanced the level of LC3II and acidic vesicular organelles-containing cells in OCs, whereas an autophagy inhibitor, 3-methyladenine (3-MA), reversed these, indicating that enhanced autophagy was responsible for the effects of DOX. Increased mitochondrial reactive oxygen species (mROS) by DOX oxidized transient receptor potential mucolipin 1 (TRPML1) on the lysosomal membrane, which led to nuclear localization of transcription factor EB (TFEB), an autophagy-inducing transcription factor. In vivo, micro-computerized tomography analysis revealed that the injection of 3-MA reversed DOX-induced bone loss, and tartrate-resistant acid phosphatase staining showed that 3-MA reduced the area of OCs on the bone surface, which was enhanced upon DOX administration. Collectively, DOX-induced bone loss is at least partly attributable to autophagy upregulation in OCs via an mROS/TRPML1/TFEB axis. Full article
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Article
Measurement of Tetrahydrobiopterin in Animal Tissue Samples by HPLC with Electrochemical Detection—Protocol Optimization and Pitfalls
Antioxidants 2022, 11(6), 1182; https://doi.org/10.3390/antiox11061182 - 16 Jun 2022
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Abstract
Tetrahydrobiopterin (BH4) is an essential cofactor of all nitric oxide synthase isoforms, thus determination of BH4 levels can provide important mechanistic insight into diseases. We established a protocol for high-performance liquid chromatography/electrochemical detection (HPLC/ECD)-based determination of BH4 in tissue samples. We first determined [...] Read more.
Tetrahydrobiopterin (BH4) is an essential cofactor of all nitric oxide synthase isoforms, thus determination of BH4 levels can provide important mechanistic insight into diseases. We established a protocol for high-performance liquid chromatography/electrochemical detection (HPLC/ECD)-based determination of BH4 in tissue samples. We first determined the optimal storage and work-up conditions for authentic BH4 and its oxidation product dihydrobiopterin (BH2) under various conditions (pH, temperature, presence of antioxidants, metal chelators, and storage time). We then applied optimized protocols for detection of BH4 in tissues of septic (induced by lipopolysaccharide [LPS]) rats. BH4 standards in HCl are stabilized by addition of 1,4-dithioerythritol (DTE) and diethylenetriaminepentaacetic acid (DTPA), while HCl was sufficient for BH2 standard stabilization. Overnight storage of BH4 standard solutions at room temperature in HCl without antioxidants caused complete loss of BH4 and the formation of BH2. We further optimized the protocol to separate ascorbate and the BH4 tissue sample and found a significant increase in BH4 in the heart and kidney as well as higher BH4 levels by trend in the brain of septic rats compared to control rats. These findings correspond to reports on augmented nitric oxide and BH4 levels in both animals and patients with septic shock. Full article
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Article
Simple and Sensitive Method for the Quantitative Determination of Lipid Hydroperoxides by Liquid Chromatography/Mass Spectrometry
Antioxidants 2022, 11(2), 229; https://doi.org/10.3390/antiox11020229 - 25 Jan 2022
Cited by 1 | Viewed by 1108
Abstract
Lipid hydroperoxides (LOOH) are the initial products of the peroxidation of unsaturated lipids and play a crucial role in lipid oxidation due to their ability to decompose into free radicals and cause adverse effects on human health. Thus, LOOHs are commonly considered biomarkers [...] Read more.
Lipid hydroperoxides (LOOH) are the initial products of the peroxidation of unsaturated lipids and play a crucial role in lipid oxidation due to their ability to decompose into free radicals and cause adverse effects on human health. Thus, LOOHs are commonly considered biomarkers of oxidative stress-associated pathological conditions. Despite their importance, the sensitive and selective analytical method for determination is limited, due to their low abundance, poor stability, and low ionizing efficiency. To overcome these limitations, in this study, we chemically synthesized eight fatty acid hydroperoxides (FAOOH), including FA 18:1-OOH, FA 18:2-OOH, FA 18:3-OOH, FA 20:4-OOH, FA 20:5-OOH, FA 22:1-OOH, FA 22:6-OOH as analytes, and FA 19:1-OOH as internal standard. Then, they were chemically labeled with 2-methoxypropene (2-MxP) to obtain FAOOMxP by one-step derivatization (for 10 min). A selected reaction monitoring assisted targeted analytical method was developed using liquid chromatography/tandem mass spectrometry (LC-MS/MS). The MxP-labelling improved the stability and enhanced the ionization efficiency in positive mode. Application of reverse-phase chromatography allowed coelution of analytes and internal standards with a short analysis time of 6 min. The limit of detection and quantification for FAOOH ranged from 0.1–1 pmol/µL and 1–2.5 pmol/µL, respectively. The method was applied to profile total FAOOHs in chemically oxidized human serum samples (n = 5) and their fractions of low and high-density lipoproteins (n = 4). The linoleic acid hydroperoxide (FA 18:2-OOH) and oleic acid hydroperoxide (FA 18:1-OOH) were the most abundant FAOOHs in human serum and lipoproteins. Overall, our validated LC-MS/MS methodology features enhanced detection and rapid separation that enables facile quantitation of multiple FAOOHs, therefore providing a valuable tool for determining the level of lipid peroxidation with potential diagnostic applications. Full article
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Review

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Review
Extracellular Vesicles and Cancer Therapy: Insights into the Role of Oxidative Stress
Antioxidants 2022, 11(6), 1194; https://doi.org/10.3390/antiox11061194 - 17 Jun 2022
Viewed by 494
Abstract
Oxidative stress plays a significant role in cancer development and cancer therapy, and is a major contributor to normal tissue injury. The unique characteristics of extracellular vesicles (EVs) have made them potentially useful as a diagnostic tool in that their molecular content indicates [...] Read more.
Oxidative stress plays a significant role in cancer development and cancer therapy, and is a major contributor to normal tissue injury. The unique characteristics of extracellular vesicles (EVs) have made them potentially useful as a diagnostic tool in that their molecular content indicates their cell of origin and their lipid membrane protects the content from enzymatic degradation. In addition to their possible use as a diagnostic tool, their role in how normal and diseased cells communicate is of high research interest. The most exciting area is the association of EVs, oxidative stress, and pathogenesis of numerous diseases. However, the relationship between oxidative stress and oxidative modifications of EVs is still unclear, which limits full understanding of the clinical potential of EVs. Here, we discuss how EVs, oxidative stress, and cancer therapy relate to one another; how oxidative stress can contribute to the generation of EVs; and how EVs’ contents reveal the presence of oxidative stress. We also point out the potential promise and limitations of using oxidatively modified EVs as biomarkers of cancer and tissue injury with a focus on pediatric oncology patients. Full article
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