Antioxidants

Editorial

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5 pages, 197 KiB

Open AccessEditorial

Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease

by Mario Allegra

Antioxidants 2021, 10(12), 1955; https://doi.org/10.3390/antiox10121955 - 7 Dec 2021

Cited by 3 | Viewed by 2544

Abstract

Reactive oxygen and nitrogen species (RONS) play a key role in the regulation of cell survival [...] Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

Research

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17 pages, 2875 KiB

Open AccessArticle

Anti-Atherosclerotic Effect of Gossypetin on Abnormal Vascular Smooth Muscle Cell Proliferation and Migration

by Hui-Hsuan Lin, Ming-Chang Hsieh, Chi-Ping Wang, Pei-Rong Yu, Ming-Shih Lee and Jing-Hsien Chen

Antioxidants 2021, 10(9), 1357; https://doi.org/10.3390/antiox10091357 - 26 Aug 2021

Cited by 13 | Viewed by 2755

Abstract

Gossypetin (GTIN), known as 3,5,7,8,3′,4′-hexahydroxyflavone, has been demonstrated to exert anti-atherosclerotic potential against apoptotic injury in oxidized low-density lipoprotein-incubated endothelial cells, and atherosclerotic lesions of cholesterol-fed rabbits. However, the effect and underlying mechanism of GTIN on abnormal vascular smooth muscle cells (VSMCs) proliferation [...] Read more.

Gossypetin (GTIN), known as 3,5,7,8,3′,4′-hexahydroxyflavone, has been demonstrated to exert anti-atherosclerotic potential against apoptotic injury in oxidized low-density lipoprotein-incubated endothelial cells, and atherosclerotic lesions of cholesterol-fed rabbits. However, the effect and underlying mechanism of GTIN on abnormal vascular smooth muscle cells (VSMCs) proliferation and migration, a major event in the pathogenesis of atherosclerosis, is still unknown. In this study, non-cytotoxic doses of GTIN abolished the VSMCs A7r5 proliferation and cell-cycle S phase distribution. The GTIN-arrested G0/G1 phase might be performed by increasing the expressions of phosphorylated p53 and its downstream molecules that inhibit the activation of cyclin E/cyclin-dependent kinase (cdk)-2, blocking retinoblastoma protein (Rb) phosphorylation and the subsequent dissociation of Rb/transcription factor E2F1 complex. In addition, the results indicated that GTIN inhibited VSMCs wound-healing and migratory abilities through reducing matrix metalloproteinase (MMP)-9 activity and expression, as well as down-regulating protein kinase B (PKB)/nuclear factor-kappaB (NF-κB) signaling. GTIN also revealed potential in diminishing reactive oxygen species (ROS) generation. These findings suggested the inhibitory effects of GTIN on VSMCs dysfunction could likely lead to the containment of atherosclerosis and other cardiovascular illness. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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18 pages, 10232 KiB

Open AccessArticle

Exogenous Antioxidants Impact on UV-Induced Changes in Membrane Phospholipids and the Effectiveness of the Endocannabinoid System in Human Skin Cells

by Agnieszka Gęgotek, Anna Jastrząb, Marta Dobrzyńska, Michał Biernacki and Elżbieta Skrzydlewska

Antioxidants 2021, 10(8), 1260; https://doi.org/10.3390/antiox10081260 - 6 Aug 2021

Cited by 8 | Viewed by 3295

Abstract

Natural antioxidants effectively counteract changes caused by UV radiation in human skin cells. However, their action is limited due to their lipo/hydrophilicity. Therefore, the aim of this study was to analyze the mutual protective action of hydrophilic ascorbic acid and partially lipophilic rutin [...] Read more.

Natural antioxidants effectively counteract changes caused by UV radiation in human skin cells. However, their action is limited due to their lipo/hydrophilicity. Therefore, the aim of this study was to analyze the mutual protective action of hydrophilic ascorbic acid and partially lipophilic rutin against UVA/UVB-induced changes in membranes phospholipid and endocannabinoid system in keratinocytes and fibroblasts. Obtained results clearly showed that, despite the stronger antioxidant properties of ascorbic acid, the lipid membranes were more effectively protected against UV-induced oxidation by rutin, including changes in phospholipid fatty acid levels, prevention against reactive aldehydes formation and endocannabinoids degradation. Ascorbic acid more strongly prevented UV-induced endocannabinoid receptors expression in fibroblasts, especially CB1. However, the combined action of used antioxidants resulted in the greatest cytoprotective effect, which was evident in the inflammatory marker TNFα down-regulation and increased cell viability following cell irradiation. The applied mixture of antioxidants showed a stronger protective in relation to membrane phospholipids in keratinocytes and in the endocannabinoid system in fibroblasts. In conclusion, it can be suggested that combined antioxidant capacities of ascorbic acid and rutin protects against lipid peroxidation but also decreases the UV-induced inflammation by direct interaction with the endocannabinoid system, thus increasing skin cell viability. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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27 pages, 8926 KiB

Open AccessArticle

Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels

by Violeta Popovici, Elena Matei, Georgeta Camelia Cozaru, Mariana Aschie, Laura Bucur, Dan Rambu, Teodor Costache, Iulia Elena Cucolea, Gabriela Vochita, Daniela Gherghel, Aureliana Caraiane and Victoria Badea

Antioxidants 2021, 10(8), 1171; https://doi.org/10.3390/antiox10081171 - 23 Jul 2021

Cited by 23 | Viewed by 5183

Abstract

Nowadays, numerous biomedical studies performed on natural compounds and plant extracts aim to obtain highly selective pharmacological activities without unwanted toxic effects. In the big world of medicinal plants, Usnea barbata (L) F.H. Wigg (U. barbata) and usnic acid (UA) are [...] Read more.

Nowadays, numerous biomedical studies performed on natural compounds and plant extracts aim to obtain highly selective pharmacological activities without unwanted toxic effects. In the big world of medicinal plants, Usnea barbata (L) F.H. Wigg (U. barbata) and usnic acid (UA) are well-known for their therapeutical properties. One of the most studied properties is their cytotoxicity on various tumor cells. This work aims to evaluate their cytotoxic potential on normal blood cells. Three dry U. barbata extracts in various solvents: ethyl acetate (UBEA), acetone (UBA), and ethanol (UBE) were prepared. From UBEA we isolated usnic acid with high purity by semipreparative chromatography. Then, UA, UBA, and UBE dissolved in 1% dimethyl sulfoxide (DMSO) and diluted in four concentrations were tested for their toxicity on human blood cells. The blood samples were collected from a healthy non-smoker donor; the obtained blood cell cultures were treated with the tested samples. After 24 h, the cytotoxic effect was analyzed through the mechanisms that can cause cell death: early and late apoptosis, caspase 3/7 activity, nuclear apoptosis, autophagy, reactive oxygen species (ROS) level and DNA damage. Generally, the cytotoxic effect was directly proportional to the increase of concentrations, usnic acid inducing the most significant response. At high concentrations, usnic acid and U. barbata extracts induced apoptosis and DNA damage in human blood cells, increasing ROS levels. Our study reveals the importance of prior natural products toxicity evaluation on normal cells to anticipate their limits and benefits as potential anticancer drugs. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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16 pages, 2859 KiB

Open AccessArticle

Changes in Hepatic Phospholipid Metabolism in Rats under UV Irradiation and Topically Treated with Cannabidiol

by Michał Biernacki, Anna Jastrząb and Elżbieta Skrzydlewska

Antioxidants 2021, 10(8), 1157; https://doi.org/10.3390/antiox10081157 - 21 Jul 2021

Cited by 9 | Viewed by 3285

Abstract

The liver is a key metabolic organ that is particularly sensitive to environmental factors, including UV radiation. As UV radiation induces oxidative stress and inflammation, natural compounds are under investigation as one method to counteract these consequences. The aim of this study was [...] Read more.

The liver is a key metabolic organ that is particularly sensitive to environmental factors, including UV radiation. As UV radiation induces oxidative stress and inflammation, natural compounds are under investigation as one method to counteract these consequences. The aim of this study was to assess the effect of topical application of phytocannabinoid-cannabidiol (CBD) on the skin of nude rats chronically irradiated with UVA/UVB, paying particular attention to its impact on the liver antioxidants and phospholipid metabolism. The results of this study indicate that CBD reaches the rat liver where it is then metabolized into decarbonylated cannabidiol, 7-hydroxy-cannabidiol and cannabidiol-glucuronide. CBD increased the levels of GSH and vitamin A after UVB radiation. Moreover, CBD prevents the increase of 4-hydroxynonenal and 8-iso-prostaglandin-F_2α levels in UVA-irradiated rats. As a consequence of reductions in phospholipase A2 and cyclooxygenases activity following UV irradiation, CBD upregulates the level of 2-arachidonoylglycerol and downregulates prostaglandin E2 and leukotriene B4. Finally, CBD enhances decreased level of 15-deoxy-Δ-12,14-prostaglandin J2 after UVB radiation and 15-hydroxyeicosatetraenoic acid after UVA radiation. These data show that CBD applied to the skin prevents ROS- and enzyme-dependent phospholipid metabolism in the liver of UV-irradiated rats, suggesting that it may be used as an internal organ protector. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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13 pages, 2090 KiB

Open AccessArticle

Blood Pressure-Lowering Effect of Wine Lees Phenolic Compounds Is Mediated by Endothelial-Derived Factors: Role of Sirtuin 1

by Raúl López-Fernández-Sobrino, Jorge R. Soliz-Rueda, Javier Ávila-Román, Anna Arola-Arnal, Manuel Suárez, Begoña Muguerza and Francisca Isabel Bravo

Antioxidants 2021, 10(7), 1073; https://doi.org/10.3390/antiox10071073 - 3 Jul 2021

Cited by 15 | Viewed by 3484

Abstract

The antihypertensive effect of wine lees powder (WLPW) from a Cabernet grape variety was related to its high content in flavanols and anthocyanins compounds. This study investigates the involvement of endothelial-derived factors and SIRT1 in its bioactivity. Spontaneously hypertensive rats (SHR) were orally [...] Read more.

The antihypertensive effect of wine lees powder (WLPW) from a Cabernet grape variety was related to its high content in flavanols and anthocyanins compounds. This study investigates the involvement of endothelial-derived factors and SIRT1 in its bioactivity. Spontaneously hypertensive rats (SHR) were orally administered water or WLPW (125 mg/kg bw). Posteriorly, both groups were intraperitoneally administered saline, Nω-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthesis inhibitor, indomethacin, a prostacyclin synthesis inhibitor, or sirtinol, an inhibitor of sirtuins. Blood pressure (BP) was recorded before and 6 h after WLPW administration. In an additional experiment, SHR were administered water or WLPW and endothelial expressions of eNos, Sirt1, Nox4, and Et1 were determined. The BP-lowering properties of WLPW were abolished by L-NAME and partially reduced by indomethacin, demonstrating that WLPW antihypertensive effect was mediated by changes in NO availability, although prostacyclin also contributed to this activity. Moreover, BP-lowering effect was reduced by sirtinol, indicating that WLPW decreased BP in a SIRT1-dependent manner. Furthermore, WLPW upregulated eNos and Sirt1 and downregulated Nox4 and Et1 endothelial gene expression. These results evidence the vasoprotective effect of WLPW and show that its antihypertensive effect in SHR is endothelium dependent and mediated by SIRT1. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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22 pages, 4353 KiB

Open AccessArticle

Hidrox^® and Endometriosis: Biochemical Evaluation of Oxidative Stress and Pain

by Marika Cordaro, Angela Trovato Salinaro, Rosalba Siracusa, Ramona D'Amico, Daniela Impellizzeri, Maria Scuto, Maria Laura Ontario, Livia Interdonato, Roberto Crea, Roberta Fusco, Salvatore Cuzzocrea, Rosanna Di Paola and Vittorio Calabrese

Antioxidants 2021, 10(5), 720; https://doi.org/10.3390/antiox10050720 - 4 May 2021

Cited by 27 | Viewed by 4653

Abstract

Endometriosis is a gynecological and painful condition affecting women of reproductive age. It is characterized by dysfunctional endometrium-like implants outside of the uterine cavity. The purpose of this study was to evaluate the effects of Hidrox^®, an aqueous extract of olive [...] Read more.

Endometriosis is a gynecological and painful condition affecting women of reproductive age. It is characterized by dysfunctional endometrium-like implants outside of the uterine cavity. The purpose of this study was to evaluate the effects of Hidrox^®, an aqueous extract of olive pulp containing hydroxytyrosol, on endometriotic lesions associated with pro-oxidative alterations and pain-like behaviors. Endometriosis was induced by intraperitoneal injection of uterine fragments, and Hidrox^® was administered daily. At the end of the 14-day treatment, behavioral alterations were assessed and hippocampal tissues were collected. Laparotomy was performed, and the endometrial implants were harvested for histological and biochemical analysis. Hidrox^® treatment reduced endometriotic implant area, diameter and volumes. Vehicle-treated rats showed lesional fibrosis, epithelial–mesenchymal transition and fibroblast–myofibroblast transdifferentiation, angiogenesis and pro-oxidative alterations in the peritoneal cavity. Hidrox^® treatment reduced the aniline blue-stained area, α-smooth muscle actin (α-sma) and CD34 positive expressions. Moreover, it reduced mast cell recruitment into the lesions, myeloperoxidase activity and lipid peroxidation and increased superoxide dismutase (SOD) activity and glutathione levels in the endometrial explants. In the peritoneal fluid, Hidrox^® treatment reduced interleukin (IL)-1β, IL2, IL6, tumor necrosis factor-α (TNF-α) and vascular endothelial grow factor (VEGF) levels increased by the disease. Hidrox^® administration also reduced peripheral and visceral sensibility as shown by the behavioral tests (open field test, hot plate test, elevated plus maze test and acetic-acid-induced abdominal contractions). Animals treated with Hidrox^® also showed reduced blood–brain barrier permeability and mast cell infiltration in the hippocampus, as well as astrocyte and microglia activation and brain oxidative status restoring brain-derived neurotrophic factor (BDNF) protein expression and increasing Nuclear factor erythroid 2-related factor 2 (Nfr2) nuclear translocation. In conclusion, Hidrox^® displayed potential ameliorative effects on endometriotic implants and related pain-induced behaviors due to its potent antioxidative properties. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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12 pages, 4340 KiB

Open AccessFeature PaperArticle

Protective Effects of Taurine Chloramine on Experimentally Induced Colitis: NFκB, STAT3, and Nrf2 as Potential Targets

by Seong Hoon Kim, Hye-Won Yum, Seung Hyeon Kim, Wonki Kim, Su-Jung Kim, Chaekyun Kim, Kyeojin Kim, Young-Ger Suh and Young-Joon Surh

Antioxidants 2021, 10(3), 479; https://doi.org/10.3390/antiox10030479 - 18 Mar 2021

Cited by 13 | Viewed by 4725

Abstract

Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory [...] Read more.

Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory mediators, such as chemokines and cytokines in many different types of cells. In the present study, we investigated the protective effects of TauCl on experimentally induced colon inflammation. Oral administration of TauCl protected against mouse colitis caused by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TauCl administration attenuated apoptosis in the colonic mucosa of TNBS-treated mice. This was accompanied by reduced expression of an oxidative stress marker, 4-hydroxy-2-nonenal and proinflammatory molecules including tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 in mouse colon. TauCl also inhibited activation of NFκB and STAT3, two key transcription factors mediating proinflammatory signaling. Notably, the protective effect of TauCl on oxidative stress and inflammation in the colon of TNBS-treated mice was associated with elevated activation of Nrf2 and upregulation of its target genes encoding heme oxygenase-1, NAD(P)H:quinone oxidoreductase, glutamate cysteine ligase catalytic subunit, and glutathione S-transferase. Taken together, these results suggest that TauCl exerts the protective effect against colitis through upregulation of Nrf2-dependent cytoprotective gene expression while blocking the proinflammatory signaling mediated by NFκB and STAT3. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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16 pages, 4063 KiB

Open AccessArticle

The Aqueous Extract of Polypodium leucotomos (Fernblock^®) Regulates Opsin 3 and Prevents Photooxidation of Melanin Precursors on Skin Cells Exposed to Blue Light Emitted from Digital Devices

by Mikel Portillo, Manuel Mataix, Miguel Alonso-Juarranz, Silvia Lorrio, María Villalba, Azahara Rodríguez-Luna and Salvador González

Antioxidants 2021, 10(3), 400; https://doi.org/10.3390/antiox10030400 - 6 Mar 2021

Cited by 27 | Viewed by 5204

Abstract

The effects of sun exposure on the skin and specifically those related to pigmentation disorders are well known. It has recently been shown that blue light leads to the induction of oxidative stress and long-lasting pigmentation. The protective effect of an aqueous extract [...] Read more.

The effects of sun exposure on the skin and specifically those related to pigmentation disorders are well known. It has recently been shown that blue light leads to the induction of oxidative stress and long-lasting pigmentation. The protective effect of an aqueous extract of Polypodium leucotomos (Fernblock^®) is known. Our aim was to investigate the action mechanism of Fernblock^® against pigmentation induced by blue light from digital devices. Human fibroblasts (HDF) and murine melanocytes (B16-F10) were exposed to artificial blue light (a 400–500 nm LED lamp). Cell viability, mitochondrial morphology, and the expression of the mitogen-activated protein kinase (MAPK) p38, known markers involved in the melanogenesis pathway, were evaluated. The activation of Opsin-3, a membrane protein sensitive to blue light that triggers the activation of the enzyme tyrosinase responsible for melanogenesis in melanocytes, was also analyzed. Our results demonstrated that pretreatment with Fernblock^® prevents cell death, alteration of mitochondrial morphology, and phosphorylation of p38 in HDF exposed to blue light. In addition, Fernblock^® significantly reduced the activation of Opsin-3 in melanocytes and the photo-oxidation of melanin, preventing its photodegradation. In sum, Fernblock^® exerts beneficial effects against the detrimental impact of blue light from digital devices and could prevent early photoaging, while maintaining skin homeostasis. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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12 pages, 2341 KiB

Open AccessArticle

ROS-Induced SIRT2 Upregulation Contributes to Cisplatin Sensitivity in Ovarian Cancer

by Wenyu Wang, Jihye Im, Soochi Kim, Suin Jang, Youngjin Han, Kyung-Min Yang, Seong-Jin Kim, Danny N. Dhanasekaran and Yong Sang Song

Antioxidants 2020, 9(11), 1137; https://doi.org/10.3390/antiox9111137 - 16 Nov 2020

Cited by 17 | Viewed by 3128

Abstract

Cisplatin resistance remains a significant obstacle for improving the clinical outcome of ovarian cancer patients. Recent studies have demonstrated that cisplatin is an important inducer of intracellullar reactive oxygen species (ROS), triggering cancer cell death. Sirtuin 2 (SIRT2), a member of class III [...] Read more.

Cisplatin resistance remains a significant obstacle for improving the clinical outcome of ovarian cancer patients. Recent studies have demonstrated that cisplatin is an important inducer of intracellullar reactive oxygen species (ROS), triggering cancer cell death. Sirtuin 2 (SIRT2), a member of class III NAD⁺ dependent histone deacetylases (HDACs), has been reported to be involved in regulating cancer hallmarks including drug response. In this study, we aimed to identify the role of SIRT2 in oxidative stress and cisplatin response in cancer. Two ovarian cancer cell lines featuring different sensitivities to cisplatin were used in this study. We found different expression patterns of SIRT2 in cisplatin-sensitive (A2780/S) and cisplatin-resistant (A2780/CP) cancer cells with cisplatin treatment, where SIRT2 expression was augmented only in A2780/S cells. Furthermore, cisplatin-induced ROS generation was responsible for the upregulation of SIRT2 in A2780/S cells, whereas overexpression of SIRT2 significantly enhanced the sensitivity of cisplatin-resistant counterpart cells to cisplatin. Our study proposes that targeting SIRT2 may provide new strategies to potentiate platinum-based chemotherapy in ovarian cancer patients. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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20 pages, 4497 KiB

Open AccessArticle

Gd-Complex of a Rosmarinic Acid Conjugate as an Anti-Inflammatory Theranostic Agent via Reactive Oxygen Species Scavenging

by Hee-Kyung Kim, Seonghwan Hwang, Bokyung Sung, Yeoun-Hee Kim and Yongmin Chang

Antioxidants 2020, 9(8), 744; https://doi.org/10.3390/antiox9080744 - 13 Aug 2020

Cited by 11 | Viewed by 4318

Abstract

Rosmarinic acid (RosA), an important polyphenol, is known for its antioxidant and anti-inflammatory activities. However, its application in theranostics has been rarely reported. Therefore, a new single-molecule anti-inflammatory theranostic compound containing RosA would be of great interest. A gadolinium (Gd) complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic [...] Read more.

Rosmarinic acid (RosA), an important polyphenol, is known for its antioxidant and anti-inflammatory activities. However, its application in theranostics has been rarely reported. Therefore, a new single-molecule anti-inflammatory theranostic compound containing RosA would be of great interest. A gadolinium (Gd) complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and RosA (Gd(DO3A-RosA)(H₂O)) was synthesized and examined for use as a single-molecule theranostic agent. Its kinetic stability is comparable to that of clinically used macrocyclic magnetic resonance imaging contrast agents. In addition, its relaxivity is higher than that of structurally analogous Gd-BT-DO3A. This agent was evaluated for inflammatory targeting magnetic resonance contrast and showed strong and prolonged enhancement of imaging in inflamed tissues of mice. The theranostic agent also possesses antioxidant and anti-inflammatory activities, as evidenced by reactive oxygen species scavenging, superoxide dismutase activity, and inflammatory factors. The novel RosA-conjugated Gd complex is a promising theranostic agent for the imaging of inflamed tissues, as well as for the treatment of inflammation and oxidative stress. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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18 pages, 4769 KiB

Open AccessArticle

Methanol Extract of Usnea barbata Induces Cell Killing, Apoptosis, and DNA Damage against Oral Cancer Cells through Oxidative Stress

by Jen-Yang Tang, Kuang-Han Wu, Yen-Yun Wang, Ammad Ahmad Farooqi, Hurng-Wern Huang, Shyng-Shiou F. Yuan, Ru-In Jian, Li-Yi Tsao, Po-An Chen, Fang-Rong Chang, Yuan-Bin Cheng, Hao-Chun Hu and Hsueh-Wei Chang

Antioxidants 2020, 9(8), 694; https://doi.org/10.3390/antiox9080694 - 3 Aug 2020

Cited by 31 | Viewed by 3872

Abstract

Some lichens provide the resources of common traditional medicines and show anticancer effects. However, the anticancer effect of Usnproliea barbata (U. barbata) is rarely investigated, especially for oral cancer cells. The aim of this study was to investigate the cell killing [...] Read more.

Some lichens provide the resources of common traditional medicines and show anticancer effects. However, the anticancer effect of Usnproliea barbata (U. barbata) is rarely investigated, especially for oral cancer cells. The aim of this study was to investigate the cell killing function of methanol extracts of U. barbata (MEUB) against oral cancer cells. MEUB shows preferential killing against a number of oral cancer cell lines (Ca9-22, OECM-1, CAL 27, HSC3, and SCC9) but rarely affects normal oral cell lines (HGF-1). Ca9-22 and OECM-1 cells display the highest sensitivity to MEUB and were chosen for concentration effect and time course experiments to address its cytotoxic mechanisms. MEUB induces apoptosis of oral cancer cells in terms of the findings from flow cytometric assays and Western blotting, such as subG1 accumulation, annexin V detection, and pancaspase activation as well as poly (ADP-ribose) polymerase (PARP) cleavage. MEUB induces oxidative stress and DNA damage of oral cancer cells following flow cytometric assays, such as reactive oxygen species (ROS)/mitochondrial superoxide (MitoSOX) production, mitochondrial membrane potential (MMP) depletion as well as overexpression of γH2AX and 8-oxo-2′deoxyguanosine (8-oxodG). All MEUB-induced changes in oral cancer cells were triggered by oxidative stress which was validated by pretreatment with antioxidant N-acetylcysteine (NAC). In conclusion, MEUB causes preferential killing of oral cancer cells and is associated with oxidative stress, apoptosis, and DNA damage. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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Review

Jump to: Editorial, Research

22 pages, 2342 KiB

Open AccessReview

A New Insight into an Alternative Therapeutic Approach to Restore Redox Homeostasis and Functional Mitochondria in Neurodegenerative Diseases

by Dong-Hoon Hyun and Jaewang Lee

Antioxidants 2022, 11(1), 7; https://doi.org/10.3390/antiox11010007 - 21 Dec 2021

Cited by 6 | Viewed by 3773

Abstract

Neurodegenerative diseases are accompanied by oxidative stress and mitochondrial dysfunction, leading to a progressive loss of neuronal cells, formation of protein aggregates, and a decrease in cognitive or motor functions. Mitochondrial dysfunction occurs at the early stage of neurodegenerative diseases. Protein aggregates containing [...] Read more.

Neurodegenerative diseases are accompanied by oxidative stress and mitochondrial dysfunction, leading to a progressive loss of neuronal cells, formation of protein aggregates, and a decrease in cognitive or motor functions. Mitochondrial dysfunction occurs at the early stage of neurodegenerative diseases. Protein aggregates containing oxidatively damaged biomolecules and other misfolded proteins and neuroinflammation have been identified in animal models and patients with neurodegenerative diseases. A variety of neurodegenerative diseases commonly exhibits decreased activity of antioxidant enzymes, lower amounts of antioxidants, and altered cellular signalling. Although several molecules have been approved clinically, there is no known cure for neurodegenerative diseases, though some drugs are focused on improving mitochondrial function. Mitochondrial dysfunction is caused by oxidative damage and impaired cellular signalling, including that of peroxisome proliferator-activated receptor gamma coactivator 1α. Mitochondrial function can also be modulated by mitochondrial biogenesis and the mitochondrial fusion/fission cycle. Mitochondrial biogenesis is regulated mainly by sirtuin 1, NAD⁺, AMP-activated protein kinase, mammalian target of rapamycin, and peroxisome proliferator-activated receptor γ. Altered mitochondrial dynamics, such as increased fission proteins and decreased fusion products, are shown in neurodegenerative diseases. Due to the restrictions of a target-based approach, a phenotype-based approach has been performed to find novel proteins or pathways. Alternatively, plasma membrane redox enzymes improve mitochondrial function without the further production of reactive oxygen species. In addition, inducers of antioxidant response elements can be useful to induce a series of detoxifying enzymes. Thus, redox homeostasis and metabolic regulation can be important therapeutic targets for delaying the progression of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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25 pages, 1682 KiB

Open AccessReview

Oxidative Stress and Neurodegeneration: Interconnected Processes in PolyQ Diseases

by Ioannis Gkekas, Anna Gioran, Marina Kleopatra Boziki, Nikolaos Grigoriadis, Niki Chondrogianni and Spyros Petrakis

Antioxidants 2021, 10(9), 1450; https://doi.org/10.3390/antiox10091450 - 13 Sep 2021

Cited by 22 | Viewed by 3914

Abstract

Neurodegenerative polyglutamine (polyQ) disorders are caused by trinucleotide repeat expansions within the coding region of disease-causing genes. PolyQ-expanded proteins undergo conformational changes leading to the formation of protein inclusions which are associated with selective neuronal degeneration. Several lines of evidence indicate that these [...] Read more.

Neurodegenerative polyglutamine (polyQ) disorders are caused by trinucleotide repeat expansions within the coding region of disease-causing genes. PolyQ-expanded proteins undergo conformational changes leading to the formation of protein inclusions which are associated with selective neuronal degeneration. Several lines of evidence indicate that these mutant proteins are associated with oxidative stress, proteasome impairment and microglia activation. These events may correlate with the induction of inflammation in the nervous system and disease progression. Here, we review the effect of polyQ-induced oxidative stress in cellular and animal models of polyQ diseases. Furthermore, we discuss the interplay between oxidative stress, neurodegeneration and neuroinflammation using as an example the well-known neuroinflammatory disease, Multiple Sclerosis. Finally, we review some of the pharmaceutical interventions which may delay the onset and progression of polyQ disorders by targeting disease-associated mechanisms. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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34 pages, 1740 KiB

Open AccessFeature PaperReview

N-Acetylcysteine (NAC): Impacts on Human Health

by Micaely Cristina dos Santos Tenório, Nayara Gomes Graciliano, Fabiana Andréa Moura, Alane Cabral Menezes de Oliveira and Marília Oliveira Fonseca Goulart

Antioxidants 2021, 10(6), 967; https://doi.org/10.3390/antiox10060967 - 16 Jun 2021

Cited by 206 | Viewed by 64694

Abstract

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory [...] Read more.

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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16 pages, 1016 KiB

Open AccessReview

Serum Albumin Redox States: More Than Oxidative Stress Biomarker

by Fuka Tabata, Yasuaki Wada, Satomi Kawakami and Kazuhiro Miyaji

Antioxidants 2021, 10(4), 503; https://doi.org/10.3390/antiox10040503 - 24 Mar 2021

Cited by 52 | Viewed by 4849

Abstract

Serum albumin is the most abundant circulating protein in mammals including humans. It has three isoforms according to the redox state of the free cysteine residue at position 34, named as mercaptalbumin (reduced albumin), non-mercaptalbumin-1 and -2 (oxidized albumin), respectively. The serum albumin [...] Read more.

Serum albumin is the most abundant circulating protein in mammals including humans. It has three isoforms according to the redox state of the free cysteine residue at position 34, named as mercaptalbumin (reduced albumin), non-mercaptalbumin-1 and -2 (oxidized albumin), respectively. The serum albumin redox state has long been viewed as a biomarker of systemic oxidative stress, as the redox state shifts to a more oxidized state in response to the severity of the pathological condition in various diseases such as liver diseases and renal failures. However, recent ex vivo studies revealed oxidized albumin per se could aggravate the pathological conditions. Furthermore, the possibility of the serum albumin redox state as a sensitive protein nutrition biomarker has also been demonstrated in a series of animal studies. A paradigm shift is thus ongoing in the research field of the serum albumin. This article provides an updated overview of analytical techniques for serum albumin redox state and its association with human health, focusing on recent findings. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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Open AccessReview

Post-Translational S-Nitrosylation of Proteins in Regulating Cardiac Oxidative Stress

by Xiaomeng Shi and Hongyu Qiu

Antioxidants 2020, 9(11), 1051; https://doi.org/10.3390/antiox9111051 - 28 Oct 2020

Cited by 19 | Viewed by 4242

Abstract

Like other post-translational modifications (PTMs) of proteins, S-nitrosylation has been considered a key regulatory mechanism of multiple cellular functions in many physiological and disease conditions. Emerging evidence has demonstrated that S-nitrosylation plays a crucial role in regulating redox homeostasis in the stressed heart, [...] Read more.

Like other post-translational modifications (PTMs) of proteins, S-nitrosylation has been considered a key regulatory mechanism of multiple cellular functions in many physiological and disease conditions. Emerging evidence has demonstrated that S-nitrosylation plays a crucial role in regulating redox homeostasis in the stressed heart, leading to discoveries in the mechanisms underlying the pathogenesis of heart diseases and cardiac protection. In this review, we summarize recent studies in understanding the molecular and biological basis of S-nitrosylation, including the formation, spatiotemporal specificity, homeostatic regulation, and association with cellular redox status. We also outline the currently available methods that have been applied to detect S-nitrosylation. Additionally, we synopsize the up-to-date studies of S-nitrosylation in various cardiac diseases in humans and animal models, and we discuss its therapeutic potential in cardiac protection. These pieces of information would bring new insights into understanding the role of S-nitrosylation in cardiac pathogenesis and provide novel avenues for developing novel therapeutic strategies for heart diseases. Full article

(This article belongs to the Special Issue Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease)

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