Reactive Oxygen Species (ROS) in Gastrointestinal Diseases

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 16239

Special Issue Editors

Department of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Republic of Korea
Interests: cancer; signaling; transcription factor; gene regulation; ROS; antioxidants
Special Issues, Collections and Topics in MDPI journals
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, China
Interests: molecular oncology; ROS; transcription factor; gene regulation; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
Interests: anticancer target; molecular mechanism; cell signaling pathway; gastrointestinal cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Reactive oxygen species (ROS) play critical roles in the development of various chronic and degenerative gastrointestinal diseases, such as cancer and digestive diseases. ROS, such as superoxide and hydrogen peroxide, can act as second messengers in intracellular signaling pathways in cancer cell progression and are associated with multiple signaling cascades that modulate cell proliferation, invasion, and angiogenesis.

For this Special Issue, we invite researchers to submit original research articles and review articles covering, without being limited to, the following topics:

  • Novel antioxidant molecules with a wide range of applications, such as in clinical medicines, natural compounds, synthesized compounds, and other bioactivity chemicals for gastrointestinal diseases;
  • Related mechanisms of antioxidant molecules that provide a basis for developing new antioxidant drugs;
  • The role of ROS in the development of gastrointestinal diseases.

Articles in a wide range of fields, from medicinal chemistry to biochemistry to molecular oncology to  nutrition, are welcome.

Prof. Dr. Young Do Jung
Dr. Shinan Li
Dr. Sen Lian
Guest Editors

Manuscript Submission Information

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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 2900 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.

Keywords

  • reactive oxygen species
  • gastrointestinal cancer
  • antioxidants
  • intracellular signaling
  • metastasis
  • cancer

Published Papers (9 papers)

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Research

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18 pages, 4568 KiB  
Article
Ellagic Acid Prevented Dextran-Sodium-Sulfate-Induced Colitis, Liver, and Brain Injury through Gut Microbiome Changes
by Dong-ha Kim, Ji-Su Kim, Jae-Hee Kwon, In-Sook Kwun, Moon-Chang Baek, Gi-Seok Kwon, Wiramon Rungratanawanich, Byoung-Joon Song, Do-Kyun Kim, Hyo-Jung Kwon and Young-Eun Cho
Antioxidants 2023, 12(10), 1886; https://doi.org/10.3390/antiox12101886 - 20 Oct 2023
Viewed by 1334
Abstract
Inflammatory bowel disease (IBD) affects millions of people worldwide and is considered a significant risk factor for colorectal cancer. Recent in vivo and in vitro studies reported that ellagic acid (EA) exhibits important antioxidant and anti-inflammatory properties. In this study, we investigated the [...] Read more.
Inflammatory bowel disease (IBD) affects millions of people worldwide and is considered a significant risk factor for colorectal cancer. Recent in vivo and in vitro studies reported that ellagic acid (EA) exhibits important antioxidant and anti-inflammatory properties. In this study, we investigated the preventive effects of EA against dextran sulfate sodium (DSS)-induced acute colitis, liver, and brain injury in mice through the gut–liver–brain axis. Acute colitis, liver, and brain injury were induced by treatment with 5% (w/v) DSS in the drinking water for 7 days. Freshly prepared EA (60 mg/kg/day) was orally administered, while control (CON) group mice were treated similarly by daily oral administrations with a vehicle (water). All the mice were euthanized 24 h after the final treatment with EA. The blood, liver, colon, and brain samples were collected for further histological and biochemical analyses. Co-treatment with a physiologically relevant dose (60 mg/kg/day) of EA for 7 days significantly reduced the DSS-induced gut barrier dysfunction; endotoxemia; and inflammatory gut, liver, and brain injury in mice by modulating gut microbiota composition and inhibiting the elevated oxidative and nitrative stress marker proteins. Our results further demonstrated that the preventive effect of EA on the DSS-induced IBD mouse model was mediated by blocking the NF-κB and mitogen-activated protein kinase (MAPK) pathway. Therefore, EA co-treatment significantly attenuated the pro-inflammatory and oxidative stress markers by suppressing the activation of NF-κB/MAPK pathways in gut, liver, and brain injury. These results suggest that EA, effective in attenuating IBD in a mouse model, deserves further consideration as a potential therapeutic for the treatment of inflammatory diseases. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
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16 pages, 2674 KiB  
Article
Response of the Glutathione (GSH) Antioxidant Defense System to Oxidative Injury in Necrotizing Enterocolitis
by Alena Golubkova, Tyler Leiva, Katherine Snyder, Camille Schlegel, Sarah M. Bonvicino, Martin-Paul Agbaga, Richard S. Brush, Jason M. Hansen, Peter F. Vitiello and Catherine J. Hunter
Antioxidants 2023, 12(7), 1385; https://doi.org/10.3390/antiox12071385 - 05 Jul 2023
Cited by 3 | Viewed by 1329
Abstract
Necrotizing enterocolitis (NEC) is a neonatal intestinal disease associated with oxidative stress. The targets of peroxidation and the role of the innate intestinal epithelial antioxidant defense system are ill-defined. We hypothesized that oxidative stress in NEC correlates with oxidized GSH redox potentials, lipid [...] Read more.
Necrotizing enterocolitis (NEC) is a neonatal intestinal disease associated with oxidative stress. The targets of peroxidation and the role of the innate intestinal epithelial antioxidant defense system are ill-defined. We hypothesized that oxidative stress in NEC correlates with oxidized GSH redox potentials, lipid peroxidation, and a dysfunctional antioxidant system. Methods: Intestinal samples from infants +/− NEC were generated into enteroids and incubated with lipopolysaccharide (LPS) and hypoxia to induce experimental NEC. HPLC assayed GSH redox potentials. Lipid peroxidation was measured by flow cytometry. Immunoblotting measured glutathione peroxidase 4 (Gpx4) expression. Results: GSH redox potentials were more oxidized in NEC intestinal tissue and enteroids as compared to controls. Lipid radicals in NEC-induced enteroids were significantly increased. Human intestinal tissue with active NEC and treated enteroid cultures revealed decreased levels of Gpx4. Conclusions: The ability of neonatal intestine to mitigate radical accumulation plays a role in its capacity to overcome oxidative stress. Accumulation of lipid radicals is confirmed after treatment of enteroids with NEC-triggering stimuli. Decreased Gpx4 diminishes a cell’s ability to effectively neutralize lipid radicals. When lipid peroxidation overwhelms antioxidant machinery, cellular death ensues. Identification of the mechanisms behind GSH-dependent enzyme dysfunction in NEC may provide insights into strategies for reversing radical damage. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
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13 pages, 286 KiB  
Article
Effects of Sihuang Zhili Granules on the Diarrhea Symptoms, Immunity, and Antioxidant Capacity of Poultry Challenged with Lipopolysaccharide (LPS)
by Shaolong Wang, Chong Li, Chaosheng Zhang, Guohua Liu, Aijuan Zheng, Kai Qiu, Wenhuan Chang and Zhimin Chen
Antioxidants 2023, 12(7), 1372; https://doi.org/10.3390/antiox12071372 - 30 Jun 2023
Cited by 1 | Viewed by 1162
Abstract
A growing interest has been focused on Chinese herbs as alternatives to antimicrobial growth promoters, which are characterized by non-toxic side effects and drug resistance. The purpose of this study was to evaluate the effects of the Sihuang Zhili granule (abbreviated as Sihuang) [...] Read more.
A growing interest has been focused on Chinese herbs as alternatives to antimicrobial growth promoters, which are characterized by non-toxic side effects and drug resistance. The purpose of this study was to evaluate the effects of the Sihuang Zhili granule (abbreviated as Sihuang) on diarrhea, immunity, and antioxidation in poultry. Thirty male Leghorn chickens, aged 21 days, were randomly assigned to one of three groups with ten animals each. The control group (CON) received intraperitoneal saline injections, while the LPS-challenged group (LPS) and Sihuang intervention group (SH) received intraperitoneal injections of LPS (0.5 mg/kg of BW) and Sihuang (5 g/kg) at d 31, d 33, d 35, respectively. The control and LPS groups were fed a basal diet, while the SH group was fed a diet supplemented with Sihuang from d 21 to d 35. Analysis of the diarrhea index showed that the addition of Sihuang inhibited the increase in the diarrhea grade and the fecal water content caused by LPS, effectively alleviating poultry diarrhea symptoms. The results of the immune and antioxidant indexes showed that Sihuang significantly reduced the contents of the pro-inflammatory factors TNF- α and IL-1 β, as well as the oxidative stress markers ROS and MDA. Conversely, it increased the contents of the anti-inflammatory factors IL-4 and IL-10, along with the activities of antioxidant enzymes GSH-Px and CAT, thereby enhancing the immune and antioxidant abilities of chickens. Furthermore, Sihuang protected the chicken’s ileum, liver, and immune organs from LPS invasion and maintained their normal development. In conclusion, this study confirmed the antidiarrheal effect of Sihuang in poultry farming and demonstrated its ability to improve poultry immunity and antioxidant capacity by modulating antioxidant enzyme activity and inflammatory cytokine levels. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
21 pages, 5024 KiB  
Article
AGS Gastric Cells: Antioxidant Activity and Metabolic Effects of Phenolic Extracts from Different Monocultivar Virgin Olive Oils
by Paola Faraoni, Maria Bellumori, Lorenzo Cecchi, Beatrice Zonfrillo, Marzia Innocenti, Alessio Gnerucci, Nadia Mulinacci and Francesco Ranaldi
Antioxidants 2023, 12(7), 1347; https://doi.org/10.3390/antiox12071347 - 27 Jun 2023
Cited by 1 | Viewed by 984
Abstract
The effects of the phenolic compounds of extra virgin olive oil (EVOO) on AGS cells have never been studied so far, which is the aim of this study. The profiles of the main phenolic components in EVOOs, mainly secoiridoid compounds derived from the [...] Read more.
The effects of the phenolic compounds of extra virgin olive oil (EVOO) on AGS cells have never been studied so far, which is the aim of this study. The profiles of the main phenolic components in EVOOs, mainly secoiridoid compounds derived from the transformation of oleuropein during the olive milling process, were evaluated and compared. Oils of different origins were evaluated aiming at verifying whether chemical differences in the phenolic composition of the dry extracts played a role in the metabolism and in maintaining the cellular redox state of AGS cells. The following key enzymes of some metabolic pathways were studied: lactate dehydrogenase, enolase, pyruvate kinase, glucose 6-phosphate dehydrogenase, citrate synthase, 3-Hydroxyacyl-CoA dehydrogenase and hexokinase. As confirmed through PCA analysis, pretreatments with the dry extracts of EVOOs at different concentrations appeared to be able to counteract the enzymatic activity alterations due to oxidative stress induced by H2O2 1 mM and 2 mM. The studied phytocomplexes showed the ability to protect AGS cells from oxidative damage and the secoiridoid derivatives from both oleuropein and ligstroside contributed to the observed effects. The results suggested that EVOOs with medium to high concentrations of phenols can exert this protection. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
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12 pages, 1950 KiB  
Article
Therapeutic Potential of Seaweed-Derived Laminaran: Attenuation of Clinical Drug Cytotoxicity and Reactive Oxygen Species Scavenging
by Hiromi Kurokawa, Thomas Kiran Marella, Hirofumi Matsui, Yutaka Kuroki and Makoto M. Watanabe
Antioxidants 2023, 12(7), 1328; https://doi.org/10.3390/antiox12071328 - 23 Jun 2023
Cited by 1 | Viewed by 1079
Abstract
β-glucan has been shown to be effective for several diseases such as immune regulation and blood pressure suppression. Seaweed contains a β-1,3/1,6-glucan called laminaran. The present commercial source of β-glucan is black yeast; however, a fermentation process using organic carbon substrates makes production [...] Read more.
β-glucan has been shown to be effective for several diseases such as immune regulation and blood pressure suppression. Seaweed contains a β-1,3/1,6-glucan called laminaran. The present commercial source of β-glucan is black yeast; however, a fermentation process using organic carbon substrates makes production unsustainable, whereas macroalgae provide a sustainable alternative with the use of CO2 and seawater as growth substrates. However, bioactivity studies on laminaran are limited. We aimed to evaluate whether laminaran can scavenge reactive oxygen species (ROS) and attenuate cytotoxicity caused by clinical drugs such as indomethacin (Ind) and dabigatran (Dab). Electron spin resonance assay revealed that laminaran scavenged singlet oxygen (1O2) and superoxide anions (O2) directly but did not scavenge hydroxyl radicals (OH). Mitochondrial ROS detection dye showed that laminaran scavenged mitochondrial O2 produced upon administration of Ind or Dab. Moreover, significant reductions in OH and peroxynitrate (ONOO) levels were observed. Since OH and ONOO are generated from O2 in the cells, laminaran could indirectly suppress the generation of OH and ONOO via the removal of O2. Both Ind and Dab induce cell injury via ROS production. Laminaran attenuated the cytotoxicity derived from these drugs and may represent a functional food with anti-aging and disease prevention properties. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
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16 pages, 1793 KiB  
Article
Germination and Simulated Gastrointestinal Digestion of Chickpea (Cicer arietinum L.) in Exhibiting In Vitro Antioxidant Activity in Gastrointestinal Epithelial Cells
by Ashley Newton and Kaustav Majumder
Antioxidants 2023, 12(5), 1114; https://doi.org/10.3390/antiox12051114 - 18 May 2023
Cited by 1 | Viewed by 1599
Abstract
Plant-based proteins, in particular pulse proteins, have grown in popularity worldwide. Germination, or sprouting, is an effective method to release peptides and other dietary compounds. However, the combination of germination and gastrointestinal digestion in enhancing the release of dietary compounds with potential health-beneficial [...] Read more.
Plant-based proteins, in particular pulse proteins, have grown in popularity worldwide. Germination, or sprouting, is an effective method to release peptides and other dietary compounds. However, the combination of germination and gastrointestinal digestion in enhancing the release of dietary compounds with potential health-beneficial biological activity has yet to be entirely elucidated. The present study illustrates the impact of germination and gastrointestinal digestion on the release of dietary compounds with antioxidant activity from chickpeas (Cicer arietinum L.). Germination up to 3 days (D0 to D3) increased the peptide content by denaturing chickpea storage proteins and increased the degree of hydrolysis (DH) in the gastric phase. The antioxidant activity was measured at three different dosages (10, 50, and 100 μg/mL) and compared between D0 and D3 on human colorectal adenocarcinoma cells (HT-29). A significant increase in antioxidant activity was observed in the D3 germinated samples in all three tested dosages. Further analysis identified 10 peptides and 7 phytochemicals differentially expressed between the D0 and D3 germinated samples. Among the differentially expressed compounds, 3 phytochemicals (2′,4′-dihydroxy-3,4-dimethoxychalcone, isoliquiritigenin 4-methyl ether, and 3-methoxy-4,2′,5′-trihydroxychalcone) and 1 peptide (His-Ala-Lys) were identified only in the D3 samples, indicating their potential contribution towards the observed antioxidant activity. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
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15 pages, 4070 KiB  
Article
Fermented Glutinous Rice Extract Mitigates DSS-Induced Ulcerative Colitis by Alleviating Intestinal Barrier Function and Improving Gut Microbiota and Inflammation
by Kwang-Youn Kim, Jae Dong Son, Su-Jin Hwang, Jong Kwang Lee, Jae Young Park, Kwang Il Park and Tae Woo Oh
Antioxidants 2023, 12(2), 336; https://doi.org/10.3390/antiox12020336 - 31 Jan 2023
Cited by 6 | Viewed by 2037
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease caused by various factors, including intestinal inflammation and barrier dysfunction. Herein, we determined the effects of fermented glutinous rice (FGR) on the expression of tight junction proteins and levels of inflammation and apoptosis in the [...] Read more.
Ulcerative colitis (UC) is an inflammatory bowel disease caused by various factors, including intestinal inflammation and barrier dysfunction. Herein, we determined the effects of fermented glutinous rice (FGR) on the expression of tight junction proteins and levels of inflammation and apoptosis in the dextran sodium sulfate (DSS)-induced acute colitis model. FGR was orally administered once per day to C57BL/6J mice with colitis induced by 5% DSS in drinking water. FGR administration recovered DSS-induced body weight loss and irregularly short colon lengths. FGR inhibited the DSS-induced decrease in FITC-dextran (FD)-4 permeability and myeloperoxidase activity. Moreover, FGR treatment repaired the reduction of zonula occluden-1 (ZO-1) and occludin expression and the increase in claudin-2 expression in colonic tissue relative to that following DSS administration. FGR treatment significantly recovered expression of cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, in serum or respective mRNA expression in colonic tissue relative to that following DSS administration. FGR regulated levels of oxidative stress-related factors, such as malondialdehyde and glutathione, and the activity of catalase and superoxide dismutase in the colon tissue of the DSS-induced acute colitis mice model. Furthermore, FGR treatment inhibited apoptosis by reducing the activity of caspase-3 and the ratio of Bcl-2 associated X (Bax)/B-cell lymphoma 2 (Bcl-2). Collectively, FGR treatment protected the intestinal barrier from dysfunction and inhibited inflammation and apoptosis in DSS-induced colitis. Therefore, FGR may decrease the inflammatory response and be a candidate for treating and prevention inflammatory bowel disease by protecting the intestinal integrity. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
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Review

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27 pages, 2228 KiB  
Review
Reactive Oxygen Species and H. pylori Infection: A Comprehensive Review of Their Roles in Gastric Cancer Development
by Dhiraj Kumar Sah, Archana Arjunan, Bora Lee and Young Do Jung
Antioxidants 2023, 12(9), 1712; https://doi.org/10.3390/antiox12091712 - 02 Sep 2023
Viewed by 1369
Abstract
Gastric cancer (GC) is the fifth most common cancer worldwide and makes up a significant component of the global cancer burden. Helicobacter pylori (H. pylori) is the most influential risk factor for GC, with the International Agency for Research on Cancer [...] Read more.
Gastric cancer (GC) is the fifth most common cancer worldwide and makes up a significant component of the global cancer burden. Helicobacter pylori (H. pylori) is the most influential risk factor for GC, with the International Agency for Research on Cancer classifying it as a Class I carcinogen for GC. H. pylori has been shown to persist in stomach acid for decades, causing damage to the stomach’s mucosal lining, altering gastric hormone release patterns, and potentially altering gastric function. Epidemiological studies have shown that eliminating H. pylori reduces metachronous cancer. Evidence shows that various molecular alterations are present in gastric cancer and precancerous lesions associated with an H. pylori infection. However, although H. pylori can cause oxidative stress-induced gastric cancer, with antioxidants potentially being a treatment for GC, the exact mechanism underlying GC etiology is not fully understood. This review provides an overview of recent research exploring the pathophysiology of H. pylori-induced oxidative stress that can cause cancer and the antioxidant supplements that can reduce or even eliminate GC occurrence. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
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27 pages, 2923 KiB  
Review
Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?
by Lei Li, Peilan Peng, Ning Ding, Wenhui Jia, Canhua Huang and Yong Tang
Antioxidants 2023, 12(4), 967; https://doi.org/10.3390/antiox12040967 - 20 Apr 2023
Cited by 14 | Viewed by 4241
Abstract
Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted and associated with oxidative stress, unbalanced gut microbiota, and aberrant immune response. Indeed, oxidative stress can affect the progression and development of IBD [...] Read more.
Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted and associated with oxidative stress, unbalanced gut microbiota, and aberrant immune response. Indeed, oxidative stress can affect the progression and development of IBD by regulating the homeostasis of the gut microbiota and immune response. Therefore, redox-targeted therapy is a promising treatment option for IBD. Recent evidence has verified that Chinese herbal medicine (CHM)-derived polyphenols, natural antioxidants, are able to maintain redox equilibrium in the intestinal tract to prevent abnormal gut microbiota and radical inflammatory responses. Here, we provide a comprehensive perspective for implementing natural antioxidants as potential IBD candidate medications. In addition, we demonstrate novel technologies and stratagems for promoting the antioxidative properties of CHM-derived polyphenols, including novel delivery systems, chemical modifications, and combination strategies. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
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