Antioxidants

Editorial

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6 pages, 259 KiB

Open AccessEditorial

Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators

by Elena Obrador and Alegría Montoro

Antioxidants 2023, 12(6), 1219; https://doi.org/10.3390/antiox12061219 - 5 Jun 2023

Cited by 8 | Viewed by 2717

Abstract

Ionizing radiation (IR) is the energy released by atoms in the form of electromagnetic waves (e [...] Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

Research

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16 pages, 2078 KiB

Open AccessArticle

A Study on the Planarian Model Confirms the Antioxidant Properties of Tameron against X-ray- and Menadione-Induced Oxidative Stress

by Elena Tsarkova, Kristina Filippova, Vera Afanasyeva, Olga Ermakova, Anastasia Kolotova, Artem Blagodatski and Artem Ermakov

Antioxidants 2023, 12(4), 953; https://doi.org/10.3390/antiox12040953 - 18 Apr 2023

Cited by 1 | Viewed by 2613

Abstract

Ionizing radiation and radiation-related oxidative stress are two important factors responsible for the death of actively proliferating cells, thus drastically reducing the regeneration capacity of living organisms. Planarian flatworms are freshwater invertebrates that are rich in stem cells called neoblasts and, therefore, present [...] Read more.

Ionizing radiation and radiation-related oxidative stress are two important factors responsible for the death of actively proliferating cells, thus drastically reducing the regeneration capacity of living organisms. Planarian flatworms are freshwater invertebrates that are rich in stem cells called neoblasts and, therefore, present a well-established model for studies on regeneration and the testing of novel antioxidant and radioprotective substances. In this work, we tested an antiviral and antioxidant drug Tameron (Monosodium α-Luminol or 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt) for its ability to reduce the harm of X-ray- and chemically induced oxidative stress on a planarian model. Our study has revealed the ability of Tameron to effectively protect planarians from oxidative stress while enhancing their regenerative capacity by modulating the expression of neoblast marker genes and NRF-2-controlled oxidative stress response genes. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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17 pages, 6085 KiB

Open AccessArticle

Limnospira indica PCC 8005 Supplementation Prevents Pelvic Irradiation-Induced Dysbiosis but Not Acute Inflammation in Mice

by Charlotte Segers, Mohamed Mysara, Amelie Coolkens, Shari Wouters, Sarah Baatout, Natalie Leys, Sarah Lebeer, Mieke Verslegers and Felice Mastroleo

Antioxidants 2023, 12(3), 572; https://doi.org/10.3390/antiox12030572 - 24 Feb 2023

Cited by 5 | Viewed by 2355

Abstract

Pelvic irradiation-induced mucositis secondarily leads to dysbiosis, which seriously affects patients’ quality of life after treatment. No safe and effective radioprotector or mitigator has yet been approved for clinical therapy. Here, we investigated the potential protective effects of fresh biomass of Limnospira indica [...] Read more.

Pelvic irradiation-induced mucositis secondarily leads to dysbiosis, which seriously affects patients’ quality of life after treatment. No safe and effective radioprotector or mitigator has yet been approved for clinical therapy. Here, we investigated the potential protective effects of fresh biomass of Limnospira indica PCC 8005 against ionizing irradiation-induced mucositis and dysbiosis in respect to benchmark probiotic Lacticaseibacillus rhamnosus GG ATCC 53103. For this, mice were supplemented daily before and after 12 Gy X-irradiation of the pelvis. Upon sacrifice, food supplements’ efficacy was assessed for intestinal barrier protection, immunomodulation and changes in the microbiota composition. While both could not confer barrier protection or significant immunomodulatory effects, 16S microbial profiling revealed that L. indica PCC 8005 and L. rhamnosus GG could prevent pelvic irradiation-induced dysbiosis. Altogether, our data show that—besides benchmarked L. rhamnosus GG—L. indica PCC 8005 is an interesting candidate to further explore as a radiomitigator counteracting pelvic irradiation-induced dysbiosis in the presented in vivo irradiation–gut–microbiota platform. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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21 pages, 2088 KiB

Open AccessArticle

Radiation Type- and Dose-Specific Transcriptional Responses across Healthy and Diseased Mammalian Tissues

by Eftychia Sagkrioti, Gökay Mehmet Biz, Işıl Takan, Seyedehsadaf Asfa, Zacharenia Nikitaki, Vassiliki Zanni, Rumeysa Hanife Kars, Christine E. Hellweg, Edouard I. Azzam, Stella Logotheti, Athanasia Pavlopoulou and Alexandros G. Georgakilas

Antioxidants 2022, 11(11), 2286; https://doi.org/10.3390/antiox11112286 - 18 Nov 2022

Cited by 14 | Viewed by 3163

Abstract

Ionizing radiation (IR) is a genuine genotoxic agent and a major modality in cancer treatment. IR disrupts DNA sequences and exerts mutagenic and/or cytotoxic properties that not only alter critical cellular functions but also impact tissues proximal and distal to the irradiated site. [...] Read more.

Ionizing radiation (IR) is a genuine genotoxic agent and a major modality in cancer treatment. IR disrupts DNA sequences and exerts mutagenic and/or cytotoxic properties that not only alter critical cellular functions but also impact tissues proximal and distal to the irradiated site. Unveiling the molecular events governing the diverse effects of IR at the cellular and organismal levels is relevant for both radiotherapy and radiation protection. Herein, we address changes in the expression of mammalian genes induced after the exposure of a wide range of tissues to various radiation types with distinct biophysical characteristics. First, we constructed a publicly available database, termed RadBioBase, which will be updated at regular intervals. RadBioBase includes comprehensive transcriptomes of mammalian cells across healthy and diseased tissues that respond to a range of radiation types and doses. Pertinent information was derived from a hybrid analysis based on stringent literature mining and transcriptomic studies. An integrative bioinformatics methodology, including functional enrichment analysis and machine learning techniques, was employed to unveil the characteristic biological pathways related to specific radiation types and their association with various diseases. We found that the effects of high linear energy transfer (LET) radiation on cell transcriptomes significantly differ from those caused by low LET and are consistent with immunomodulation, inflammation, oxidative stress responses and cell death. The transcriptome changes also depend on the dose since low doses up to 0.5 Gy are related with cytokine cascades, while higher doses with ROS metabolism. We additionally identified distinct gene signatures for different types of radiation. Overall, our data suggest that different radiation types and doses can trigger distinct trajectories of cell-intrinsic and cell-extrinsic pathways that hold promise to be manipulated toward improving radiotherapy efficiency and reducing systemic radiotoxicities. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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12 pages, 1492 KiB

Open AccessArticle

Antioxidant Potential of Resveratrol as the Result of Radiation Exposition

by Natalia Rosiak, Judyta Cielecka-Piontek, Robert Skibiński, Kornelia Lewandowska, Waldemar Bednarski and Przemysław Zalewski

Antioxidants 2022, 11(11), 2097; https://doi.org/10.3390/antiox11112097 - 24 Oct 2022

Cited by 8 | Viewed by 2970

Abstract

The purpose of this study was to determine the effect of electron beam irradiation (EBI) at a dose of 25 kGy on the stability and antioxidant properties of resveratrol (RSV), a nutraceutical with clinically proven activity. The electron paramagnetic resonance (EPR) method was [...] Read more.

The purpose of this study was to determine the effect of electron beam irradiation (EBI) at a dose of 25 kGy on the stability and antioxidant properties of resveratrol (RSV), a nutraceutical with clinically proven activity. The electron paramagnetic resonance (EPR) method was used to evaluate the concentration of free radicals after irradiation. Minor changes in chemical structure due to free radicals induced by EBI were confirmed by FTIR spectroscopy. HPLC and HPLC-MS analysis ruled out the appearance of degradation products after irradiation. In addition, HPLC analysis confirmed the absence of trans- to cis-resveratrol conversion. Changes in the antioxidant potential of RSV after irradiation were studied using DPPH, ABTS, CUPRAC, and FRAP techniques. It was confirmed that EBI favorably affected the antioxidant properties of tests based on the HAT mechanism (increase in DPPH and CUPRAC tests). Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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24 pages, 10270 KiB

Open AccessArticle

New Properties of a Well-Known Antioxidant: Pleiotropic Effects of Human Lactoferrin in Mice Exposed to Gamma Irradiation in a Sublethal Dose

by Marina Yu. Kopaeva, Irina B. Alchinova, Anton B. Cherepov, Marina S. Demorzhi, Mikhail V. Nesterenko, Irina Yu. Zarayskaya and Mikhail Yu. Karganov

Antioxidants 2022, 11(9), 1833; https://doi.org/10.3390/antiox11091833 - 18 Sep 2022

Cited by 10 | Viewed by 2526

Abstract

We studied the effects of human lactoferrin (hLf), a multifunctional protein from the transferrin family, on integral (survival, lifespan during the experiment, body weight, behavior, subfractional compositions of blood serum) and systemic (hemoglobin level, leukocyte number, differential leukocyte count, histological structure of the [...] Read more.

We studied the effects of human lactoferrin (hLf), a multifunctional protein from the transferrin family, on integral (survival, lifespan during the experiment, body weight, behavior, subfractional compositions of blood serum) and systemic (hemoglobin level, leukocyte number, differential leukocyte count, histological structure of the liver and spleen) parameters of the body in mice after acute gamma irradiation in a sublethal dose. The experiments were performed on male C57BL/6 mice. The mice in the experimental groups were exposed to whole-body gamma radiation in a dose of 7.5 Gy from a ⁶⁰Co source. Immediately after irradiation and 24 h after it, some animals received an intraperitoneal injection of hLf (4 mg/mouse). Single or repeated administration of hLf had a positive pleiotropic effect on irradiated animals: animal survival increased from 28% to 78%, and the mean life expectancy during the experiment (30 days) increased from 16 to 26 days. A compensatory effect of hLf on radiation-induced body weight loss, changes in homeostasis parameters, and a protective effect on the structural organization of the spleen were demonstrated. These data indicate that Lf has potential as a means of early therapy after radiation exposure. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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14 pages, 1848 KiB

Open AccessArticle

Serum Proteomic and Oxidative Modification Profiling in Mice Exposed to Total Body X-Irradiation

by Masaru Yamaguchi, Yota Tatara, Eka Djatnika Nugraha, Yoshiaki Sato, Tomisato Miura, Masahiro Hosoda, Mukh Syaifudin, Shinji Tokonami and Ikuo Kashiwakura

Antioxidants 2022, 11(9), 1710; https://doi.org/10.3390/antiox11091710 - 30 Aug 2022

Cited by 5 | Viewed by 2280

Abstract

The details of the dose-dependent response of serum proteins exposed to ionizing radiation, especially the oxidative modification response in amino acid sequences of albumin, the most abundant protein, are unknown. Thus, a proteomic analysis of the serum components from mice exposed to total [...] Read more.

The details of the dose-dependent response of serum proteins exposed to ionizing radiation, especially the oxidative modification response in amino acid sequences of albumin, the most abundant protein, are unknown. Thus, a proteomic analysis of the serum components from mice exposed to total body X-irradiation (TBI) ranging from 0.5 Gy to 3.0 Gy was conducted using LC-MS/MS. The analysis of oxidative modification sequences of albumin (mOMSA) in TBI mouse serum revealed significant moderate or strong correlations between the X-irradiation exposure dose and modification of 11 mOMSAs (especially the 97th, 267th and 499th lysine residues, 159th methionine residue and 287th tyrosine residues). In the case of X-irradiation of serum alone, significant correlations were also found in the 14 mOMSAs. In addition, a dose-dependent variation in six proteins (Angiotensinogen, Odorant-binding protein 1a, Serine protease inhibitor A3K, Serum paraoxonase/arylesterase 1, Prothrombin and Epidermal growth factor receptor) was detected in the serum of mice exposed to TBI. These findings suggest the possibility that the protein variation and serum albumin oxidative modification responses found in exposed individuals are important indicators for considering the effects of radiation on living organisms, along with DNA damage, and suggests their possible application as biomarkers of radiation dose estimation. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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24 pages, 2908 KiB

Open AccessArticle

Differential Radiomodulating Action of Olea europaea L. cv. Caiazzana Leaf Extract on Human Normal and Cancer Cells: A Joint Chemical and Radiobiological Approach

by Severina Pacifico, Pavel Bláha, Shadab Faramarzi, Francesca Fede, Katarina Michaličková, Simona Piccolella, Valerio Ricciardi and Lorenzo Manti

Antioxidants 2022, 11(8), 1603; https://doi.org/10.3390/antiox11081603 - 19 Aug 2022

Cited by 11 | Viewed by 2717

Abstract

The identification of a natural compound with selectively differential radiomodulating activity would arguably represent a valuable asset in the striving quest for widening the therapeutic window in cancer radiotherapy (RT). To this end, we fully characterized the chemical profile of olive tree leaf [...] Read more.

The identification of a natural compound with selectively differential radiomodulating activity would arguably represent a valuable asset in the striving quest for widening the therapeutic window in cancer radiotherapy (RT). To this end, we fully characterized the chemical profile of olive tree leaf polyphenols from the Caiazzana cultivar (OLC), autochthonous to the Campania region (Italy), by ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HR-MS). Oleacein was the most abundant molecule in the OLC. Two normal and two cancer cells lines were X-ray-irradiated following 24-h treatment with the same concentration of the obtained crude extract and were assessed for their radioresponse in terms of micronucleus (MN) induction and, for one of the normal cell lines, of premature senescence (PS). Irradiation of pre-treated normal cells in the presence of the OLC reduced the frequency of radiation-induced MN and the onset of PS. Conversely, the genotoxic action of ionising radiation was exacerbated in cancer cells under the same experimental conditions. To our knowledge, this is the first report on the dual action of a polyphenol-rich olive leaf extract on radiation-induced damage. If further confirmed, these findings may be pre-clinically relevant and point to a substance that may potentially counteract cancer radioresistance while reducing RT-associated normal tissue toxicity. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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15 pages, 3388 KiB

Open AccessArticle

Peroxiredoxin 6 Applied after Exposure Attenuates Damaging Effects of X-ray Radiation in 3T3 Mouse Fibroblasts

by Elena G. Novoselova, Mars G. Sharapov, Sergey M. Lunin, Svetlana B. Parfenyuk, Maxim O. Khrenov, Elvira K. Mubarakshina, Anna A. Kuzekova, Tatyana V. Novoselova, Ruslan G. Goncharov and Olga V. Glushkova

Antioxidants 2021, 10(12), 1951; https://doi.org/10.3390/antiox10121951 - 5 Dec 2021

Cited by 11 | Viewed by 3496

Abstract

Although many different classes of antioxidants have been evaluated as radioprotectors, none of them are in widespread clinical use because of their low efficiency. The goal of our study was to evaluate the potential of the antioxidant protein peroxiredoxin 6 (Prdx6) to increase [...] Read more.

Although many different classes of antioxidants have been evaluated as radioprotectors, none of them are in widespread clinical use because of their low efficiency. The goal of our study was to evaluate the potential of the antioxidant protein peroxiredoxin 6 (Prdx6) to increase the radioresistance of 3T3 fibroblasts when Prdx6 was applied after exposure to 6 Gy X-ray. In the present study, we analyzed the mRNA expression profiles of genes associated with proliferation, apoptosis, cellular stress, senescence, and the production of corresponding proteins from biological samples after exposure of 3T3 cells to X-ray radiation and application of Prdx6. Our results suggested that Prdx6 treatment normalized p53 and NF-κB/p65 expression, p21 levels, DNA repair-associated genes (XRCC4, XRCC5, H2AX, Apex1), TLR expression, cytokine production (TNF-α and IL-6), and apoptosis, as evidenced by decreased caspase 3 level in irradiated 3T3 cells. In addition, Prdx6 treatment reduced senescence, as evidenced by the decreased percentage of SA-β-Gal positive cells in cultured 3T3 fibroblasts. Importantly, the activity of the NRF2 gene, an important regulator of the antioxidant cellular machinery, was completely suppressed by irradiation but was restored by post-irradiation Prdx6 treatment. These data support the radioprotective therapeutic efficacy of Prdx6. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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18 pages, 11903 KiB

Open AccessArticle

Radioprotective and Radiomitigative Effects of Melatonin in Tissues with Different Proliferative Activity

by Serazhutdin A. Abdullaev, Sergey I. Glukhov and Azhub I. Gaziev

Antioxidants 2021, 10(12), 1885; https://doi.org/10.3390/antiox10121885 - 25 Nov 2021

Cited by 11 | Viewed by 3193

Abstract

We used various markers to analyze damage to mouse tissues (spleen and cerebral cortex) which have different proliferative activity and sensitivity to ionizing radiation (IR). We also assessed the degree of modulation of damages that occurs when melatonin is administered to mice prior [...] Read more.

We used various markers to analyze damage to mouse tissues (spleen and cerebral cortex) which have different proliferative activity and sensitivity to ionizing radiation (IR). We also assessed the degree of modulation of damages that occurs when melatonin is administered to mice prior to and after their X-ray irradiation. The data from this study showed that lesions in nuclear DNA (nDNA) were repaired more actively in the spleen than in the cerebral cortex of mice irradiated and treated with melatonin (N-acetyl-5-methoxytryptamine). Mitochondrial biogenesis involving mitochondrial DNA (mtDNA) synthesis was activated in both tissues of irradiated mice. A significant proportion of the newly synthesized mtDNA molecules were mutant copies that increase oxidative stress. Melatonin reduced the number of mutant mtDNA copies and the level of H₂O₂ in both tissues of the irradiated mice. Melatonin promoted the restoration of ATP levels in the tissues of irradiated mice. In the mouse tissues after exposure to X-ray, the level of malondialdehyde (MDA) increased and melatonin was able to reduce it. The MDA concentration was higher in the cerebral cortex tissue than that in the spleen tissue of the mouse. In mouse tissues following irradiation, the glutathione (GSH) level was low. The spleen GSH content was more than twice as low as that in the cerebral cortex. Melatonin helped restore the GSH levels in the mouse tissues. Although the spleen and cerebral cortex tissues of mice differ in the baseline values of the analyzed markers, the radioprotective and radiomitigative potential of melatonin was observed in both tissues. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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12 pages, 2225 KiB

Open AccessArticle

Planarians as an In Vivo Experimental Model for the Study of New Radioprotective Substances

by Artem M. Ermakov, Kristina A. Kamenskikh, Olga N. Ermakova, Artem S. Blagodatsky, Anton L. Popov and Vladimir K. Ivanov

Antioxidants 2021, 10(11), 1763; https://doi.org/10.3390/antiox10111763 - 4 Nov 2021

Cited by 3 | Viewed by 3305

Abstract

Ionising radiation causes the death of the most actively dividing cells, thus leading to depletion of the stem cell pool. Planarians are invertebrate flatworms that are unique in that their stem cells, called neoblasts, constantly replace old, damaged, or dying cells. Amenability to [...] Read more.

Ionising radiation causes the death of the most actively dividing cells, thus leading to depletion of the stem cell pool. Planarians are invertebrate flatworms that are unique in that their stem cells, called neoblasts, constantly replace old, damaged, or dying cells. Amenability to efficient RNAi treatments, the rapid development of clear phenotypes, and sensitivity to ionising radiation, combined with new genomic technologies, make planarians an outstanding tool for the discovery of potential radioprotective agents. In this work, using the well-known antioxidant N-acetylcysteine, planarians are, for the first time, shown to be an excellent model system for the fast and effective screening of novel radioprotective and radio-sensitising substances. In addition, a panel of measurable parameters that can be used for the study of radioprotective effects on this model is suggested. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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17 pages, 5623 KiB

Open AccessArticle

Supplemental Ferulic Acid Inhibits Total Body Irradiation-Mediated Bone Marrow Damage, Bone Mass Loss, Stem Cell Senescence, and Hematopoietic Defect in Mice by Enhancing Antioxidant Defense Systems

by Sajeev Wagle, Hyun-Jaung Sim, Govinda Bhattarai, Ki-Choon Choi, Sung-Ho Kook, Jeong-Chae Lee and Young-Mi Jeon

Antioxidants 2021, 10(8), 1209; https://doi.org/10.3390/antiox10081209 - 28 Jul 2021

Cited by 15 | Viewed by 4190

Abstract

While total body irradiation (TBI) is an everlasting curative therapy, the irradiation can cause long-term bone marrow (BM) injuries, along with senescence of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) via reactive oxygen species (ROS)-induced oxidative damages. Thus, ameliorating or preventing [...] Read more.

While total body irradiation (TBI) is an everlasting curative therapy, the irradiation can cause long-term bone marrow (BM) injuries, along with senescence of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) via reactive oxygen species (ROS)-induced oxidative damages. Thus, ameliorating or preventing ROS accumulation and oxidative stress is necessary for TBI-requiring clinical treatments. Here, we explored whether administration of ferulic acid, a dietary antioxidant, protects against TBI-mediated systemic damages, and examined the possible mechanisms therein. Sublethal TBI (5 Gy) decreased body growth, lifespan, and production of circulating blood cells in mice, together with ROS accumulation, and senescence induction of BM-conserved HSCs and MSCs. TBI also impaired BM microenvironment and bone mass accrual, which was accompanied by downregulated osteogenesis and by osteoclastogenic and adipogenic activation in BM. Long-term intraperitoneal injection of ferulic acid (50 mg/kg body weight, once per day for 37 consecutive days) protected mice from TBI-mediated mortality, stem cell senescence, and bone mass loss by restoring TBI-stimulated disorders in osteogenic, osteoclastic, and adipogenic activation in BM. In vitro experiments using BM stromal cells supported radioprotective effects of ferulic acid on TBI-mediated defects in proliferation and osteogenic differentiation. Overall, treatment with ferulic acid prevented TBI-mediated liver damage and enhanced endogenous antioxidant defense systems in the liver and BM. Collectively, these results support an efficient protection of TBI-mediated systemic defects by supplemental ferulic acid, indicating its clinical usefulness for TBI-required patients. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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Review

Jump to: Editorial, Research

23 pages, 387 KiB

Open AccessReview

Combination Therapy of Radiation and Hyperthermia, Focusing on the Synergistic Anti-Cancer Effects and Research Trends

by Seeun Kwon, Sumin Jung and Seung Ho Baek

Antioxidants 2023, 12(4), 924; https://doi.org/10.3390/antiox12040924 - 13 Apr 2023

Cited by 23 | Viewed by 4321

Abstract

Despite significant therapeutic advances, the toxicity of conventional therapies remains a major obstacle to their application. Radiation therapy (RT) is an important component of cancer treatment. Therapeutic hyperthermia (HT) can be defined as the local heating of a tumor to 40–44 °C. Both [...] Read more.

Despite significant therapeutic advances, the toxicity of conventional therapies remains a major obstacle to their application. Radiation therapy (RT) is an important component of cancer treatment. Therapeutic hyperthermia (HT) can be defined as the local heating of a tumor to 40–44 °C. Both RT and HT have the advantage of being able to induce and regulate oxidative stress. Here, we discuss the effects and mechanisms of RT and HT based on experimental research investigations and summarize the results by separating them into three phases. Phase (1): RT + HT is effective and does not provide clear mechanisms; phase (2): RT + HT induces apoptosis via oxygenation, DNA damage, and cell cycle arrest; phase (3): RT + HT improves immunological responses and activates immune cells. Overall, RT + HT is an effective cancer modality complementary to conventional therapy and stimulates the immune response, which has the potential to improve cancer treatments, including immunotherapy, in the future. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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18 pages, 2138 KiB

Open AccessReview

Targeting Mitochondrial Metabolism to Reverse Radioresistance: An Alternative to Glucose Metabolism

by Chenbin Bian, Zhuangzhuang Zheng, Jing Su, Huanhuan Wang, Sitong Chang, Ying Xin and Xin Jiang

Antioxidants 2022, 11(11), 2202; https://doi.org/10.3390/antiox11112202 - 7 Nov 2022

Cited by 13 | Viewed by 3060

Abstract

Radiotherapy failure and poor tumor prognosis are primarily attributed to radioresistance. Improving the curative effect of radiotherapy and delaying cancer progression have become difficult problems for clinicians. Glucose metabolism has long been regarded as the main metabolic process by which tumor cells meet [...] Read more.

Radiotherapy failure and poor tumor prognosis are primarily attributed to radioresistance. Improving the curative effect of radiotherapy and delaying cancer progression have become difficult problems for clinicians. Glucose metabolism has long been regarded as the main metabolic process by which tumor cells meet their bioenergetic and anabolic needs, with the complex interactions between the mitochondria and tumors being ignored. This misconception was not dispelled until the early 2000s; however, the cellular molecules and signaling pathways involved in radioresistance remain incompletely defined. In addition to being a key metabolic site that regulates tumorigenesis, mitochondria can influence the radiation effects of malignancies by controlling redox reactions, participating in oxidative phosphorylation, producing oncometabolites, and triggering apoptosis. Therefore, the mitochondria are promising targets for the development of novel anticancer drugs. In this review, we summarize the internal relationship and related mechanisms between mitochondrial metabolism and cancer radioresistance, thus exploring the possibility of targeting mitochondrial signaling pathways to reverse radiation insensitivity. We suggest that attention should be paid to the potential value of mitochondria in prolonging the survival of cancer patients. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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51 pages, 1526 KiB

Open AccessReview

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

by Elena Obrador, Rosario Salvador-Palmer, Juan I. Villaescusa, Eduardo Gallego, Blanca Pellicer, José M. Estrela and Alegría Montoro

Antioxidants 2022, 11(6), 1098; https://doi.org/10.3390/antiox11061098 - 31 May 2022

Cited by 42 | Viewed by 6380

Abstract

Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are [...] Read more.

Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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16 pages, 1702 KiB

Open AccessReview

Auranofin and Pharmacologic Ascorbate as Radiomodulators in the Treatment of Pancreatic Cancer

by Garett J. Steers, Gloria Y. Chen, Brianne R. O’Leary, Juan Du, Hannah Van Beek and Joseph J. Cullen

Antioxidants 2022, 11(5), 971; https://doi.org/10.3390/antiox11050971 - 14 May 2022

Cited by 7 | Viewed by 3536

Abstract

Pancreatic cancer accounts for nearly one fourth of all new cancers worldwide. Little progress in the development of novel or adjuvant therapies has been made over the past few decades and new approaches to the treatment of pancreatic cancer are desperately needed. Pharmacologic [...] Read more.

Pancreatic cancer accounts for nearly one fourth of all new cancers worldwide. Little progress in the development of novel or adjuvant therapies has been made over the past few decades and new approaches to the treatment of pancreatic cancer are desperately needed. Pharmacologic ascorbate (P-AscH⁻, high-dose, intravenous vitamin C) is being investigated in clinical trials as an adjunct to standard-of-care chemoradiation treatments. In vitro, P-AscH⁻ has been shown to sensitize cancer cells to ionizing radiation in a manner that is dependent on the generation of H₂O₂ while simultaneously protecting normal tissue from radiation damage. There is renewed interest in Auranofin (Au), an FDA-approved medication utilized in the treatment of rheumatoid arthritis, as an anti-cancer agent. Au inhibits the thioredoxin antioxidant system, thus increasing the overall peroxide burden on cancer cells. In support of current literature demonstrating Au’s effectiveness in breast, colon, lung, and ovarian cancer, we offer additional data that demonstrate the effectiveness of Au alone and in combination with P-AscH⁻ and ionizing radiation in pancreatic cancer treatment. Combining P-AscH⁻ and Au in the treatment of pancreatic cancer may confer multiple mechanisms to increase H₂O₂-dependent toxicity amongst cancer cells and provide a promising translatable avenue by which to enhance radiation effectiveness and improve patient outcomes. Full article

(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)

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