Submit to Antioxidants Review for Antioxidants Propose a Special Issue

Journal Browser

New Strategies in Preventing Inflammatory and/or Oxidative-Stress-Induced Damages in Ischemia–Reperfusion Injury

Special Issue Editors
Special Issue Information
Published Papers

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 May 2024) | Viewed by 7763

Share This Special Issue

Special Issue Editors

Prof. Dr. Ana Alonso-Varona

E-Mail Website
Guest Editor

Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
Interests: tissue engineering; regenerative medicine; oxidative stress; ischemia-reperfusion injury; antioxidants therapy

Dr. Ignacio García-Alonso

E-Mail Website
Guest Editor

Department of Surgery, Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
Interests: liver regeneration; liver metastasis; magnetic hyperthermia; nanoparticles; ischemia-reperfusion injury; antioxidants therapy; experimental surgery

Dr. Borja Herrero de la Parte

E-Mail Website
Guest Editor

Department of Surgery, Faculty of Medicine, Complutense University of Madrid (UCM), 28040 Madrid, Spain
Interests: liver regeneration; liver metastasis; magnetic hyperthermia; nanoparticles; ischemia-reperfusion injury; antioxidants therapy; experimental surgery

Special Issue Information

Dear Colleagues,

Ischemia–reperfusion injury (IRI) is a clinical condition caused by the sudden deprivation or dramatic reduction in blood supply to an organ or tissue followed by restoration of blood flow. Sustained ischemia results in a deficient supply of oxygen, nutrients and other molecules, which generates tissue damage, which is proportional to its intensity and duration. In addition to direct cellular damage generated by hypoxia (decreased intracellular ATP and pH and increased calcium levels, among others), multiple proinflammatory molecules mobilize and recruit leukocytes, which release reactive oxygen species (ROS), endothelial activators, and proteolytic enzymes. Blood flow restoration to the ischemic territory induces by itself an exacerbation of this damage, due to a combination of several factors, such as the presence of reactive oxygen species, the action of cytokines or neutrophils, and the activation of the complement system or changes in capillary permeability.

The causes of this syndrome are diverse. IRI is an inherent condition following major cardiovascular surgeries (which leads to low cardiac output), solid organ transplants (lung, liver, etc.), or orthopedic surgeries performed under induced ischemia. However, this disorder can also suddenly originate from a vascular spasm or thromboembolism that deprives an organ or region of adequate blood supply. This condition can occur in different locations, such as the myocardium, retina, or intestine, among others. Furthermore, this syndrome does not only affect adult individuals, since IRI is also responsible for the pathological mechanisms underlying the long-term neurological damage in newborns suffering from perinatal hypoxia.

The purpose of this Special Issue of Antioxidants is to show the most recent advances in the application of therapies aimed at minimizing, reducing or even preventing IRI damage in different organs or systems, regardless of its causes. These therapies may involve both well-known natural and synthetic antioxidants, as well as new options based on the administration of stem cells or its derivative products (secretome) as therapeutic strategies. This Special Issue calls for original research papers and in-depth reviews that address i) a better understanding of the underlying molecular processes involved in IRI; ii), the progress and current status of the therapeutic management of IRI; and iii) aspects related to the preservation of the organ function, due to their special clinical interest.

Contributions need not be limited to the fields mentioned in the keywords. Authors of review papers are kindly requested to make a pre-submission inquiry with a brief outline to the Editors.

Prof. Dr. Ana Alonso-Varona
Dr. Ignacio García-Alonso
Dr. Borja Herrero de la Parte
Guest Editors

Manuscript Submission Information

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

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

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 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.

Published Papers (7 papers)

Download All Papers

Research

Jump to: Review, Other

21 pages, 1365 KiB

Open AccessArticle

Identification of New, Translatable ProtectomiRs against Myocardial Ischemia/Reperfusion Injury and Oxidative Stress: The Role of MMP/Biglycan Signaling Pathways

by Tamara Szabados, Arnold Molnár, Éva Kenyeres, Kamilla Gömöri, Judit Pipis, Bence Pósa, András Makkos, Bence Ágg, Zoltán Giricz, Péter Ferdinandy, Anikó Görbe and Péter Bencsik

Antioxidants 2024, 13(6), 674; https://doi.org/10.3390/antiox13060674 (registering DOI) - 30 May 2024

Abstract

Introduction: Ischemic conditionings (ICon) were intensively investigated and several protective signaling pathways were identified. Previously, we have shown the role of matrix metalloproteinases (MMP) in myocardial ischemia/reperfusion injury (MIRI) and the cardioprotective role of biglycan (BGN), a small leucine-rich proteoglycan in vitro. Here, we hypothesized that cardiac MMP and BGN signaling are involved in the protective effects of ICon. Methods: A reverse target-microRNA prediction was performed by using the miRNAtarget™ 2.0 software to identify human microRNAs with a possible regulatory effect on MMP and BGN, such as on related genes. To validate the identified 1289 miRNAs in the predicted network, we compared them to two cardioprotective miRNA omics datasets derived from pig and rat models of MIRI in the presence of ICons. Results: Among the experimentally measured miRNAs, we found 100% sequence identity to human predicted regulatory miRNAs in the case of 37 porcine and 24 rat miRNAs. Upon further analysis, 42 miRNAs were identified as MIRI-associated miRNAs, from which 24 miRNAs were counter-regulated due to ICons. Conclusions: Our findings highlight 24 miRNAs that potentially regulate cardioprotective therapeutic targets associated with MMPs and BGN in a highly translatable porcine model of acute myocardial infarction. Full article

(This article belongs to the Special Issue New Strategies in Preventing Inflammatory and/or Oxidative-Stress-Induced Damages in Ischemia–Reperfusion Injury)

15 pages, 2009 KiB

Open AccessArticle

S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats

by Sergio Valdés, Sergio D. Paredes, Carmen García Carreras, Pilar Zuluaga, Lisa Rancan, Beatriz Linillos-Pradillo, Javier Arias-Díaz and Elena Vara

Antioxidants 2023, 12(8), 1539; https://doi.org/10.3390/antiox12081539 - 31 Jul 2023

Cited by 1 | Viewed by 862

Abstract

Hepatic ischemia/reperfusion injury (IRI) can seriously impair liver function. It is initiated by oxidative stress, resulting in inflammation and apoptosis-induced cellular damage. Glutathione (GSH) prevents oxidative stress. S-Adenosylmethionine (SAMet) is a GSH synthesis precursor that avoids the deficit in SAMet-synthetase activity and contributes to intracellular ATP repletion. It also acts as a methyl group donor, stabilizing hepatocyte membranes, among other functions. This study investigated the effect of SAMet on bacterial translocation and levels of proinflammatory cytokines, oxidative stress and apoptosis markers in male Wistar rats subjected to hepatic IRI. Animals were randomly divided into six groups: (1) sham operation, (3) animals undergoing 60 min of ischemia of the right lateral lobe for temporary occlusion of the portal vein and hepatic artery plus 10 min of reperfusion, and (5) the same as (3) but with a reperfusion period of 120 min. Groups 2, 4 and 6, respectively, are the same as (1), (3) and (5), except that animals received SAMet (20 mg/kg) 15 min before ischemia. GSH, ATP, lipid peroxidation (LPO), TNF-α, IL-1β, IL-6, total caspase-1 and caspase-9, total and cleaved caspase-3, and phosphatidylcholine were determined in the liver. Endotoxin, TNF-α, IL-1β, IL-6, IL-10 and LPO in vena cava and portal vein blood samples were also measured. Endotoxin and LPO levels as well as proinflammatory cytokines and apoptotic markers increased significantly in animals undergoing IRI, both after 10 and 120 min of reperfusion. IRI produced a significant decrease in GSH, ATP, portal IL-10 and phosphatidylcholine. SAMet treatment prevented these effects significantly and increased survival rate. The study suggests that SAMet exerts protective effects in hepatic IRI. Full article

(This article belongs to the Special Issue New Strategies in Preventing Inflammatory and/or Oxidative-Stress-Induced Damages in Ischemia–Reperfusion Injury)

► Show Figures

Figure 1

16 pages, 34805 KiB

Open AccessArticle

Aucubin Exerts Neuroprotection against Forebrain Ischemia and Reperfusion Injury in Gerbils through Antioxidative and Neurotrophic Effects

by Joon Ha Park, Tae-Kyeong Lee, Dae Won Kim, Ji Hyeon Ahn, Choong-Hyun Lee, Soon Sung Lim, Yang Hee Kim, Jun Hwi Cho, Il Jun Kang and Moo-Ho Won

Antioxidants 2023, 12(5), 1082; https://doi.org/10.3390/antiox12051082 - 11 May 2023

Cited by 3 | Viewed by 1848

Abstract

Aucubin is an iridoid glycoside that displays various pharmacological actions including antioxidant activity. However, there are few reports available on the neuroprotective effects of aucubin against ischemic brain injury. Thus, the aim of this study was to investigate whether aucubin protected against damage to hippocampal function induced by forebrain ischemia-reperfusion injury (fIRI) in gerbils, and to examine whether aucubin produced neuroprotection in the hippocampus against fIRI and to explore its mechanisms by histopathology, immunohistochemistry, and Western analysis. Gerbils were given intraperitoneal injections of aucubin at doses of 1, 5, and 10 mg/kg, respectively, once a day for seven days before fIRI. As assessed by the passive avoidance test, short-term memory function following fIRI significantly declined, whereas the decline in short-term memory function due to fIRI was ameliorated by pretreatment with 10 mg/kg, but not 1 or 5 mg/kg, of aucubin. Most of the pyramidal cells (principal cells) of the hippocampus died in the Cornu Ammonis 1 (CA1) area four days after fIRI. Treatment with 10 mg/kg, but not 1 or 5 mg/kg, of aucubin protected the pyramidal cells from IRI. The treatment with 10 mg/kg of aucubin significantly reduced IRI-induced superoxide anion production, oxidative DNA damage, and lipid peroxidation in the CA1 pyramidal cells. In addition, the aucubin treatment significantly increased the expressions of superoxide dismutases (SOD1 and SOD2) in the pyramidal cells before and after fIRI. Furthermore, the aucubin treatment significantly enhanced the protein expression levels of neurotrophic factors, such as brain-derived neurotrophic factor and insulin-like growth factor-I, in the hippocampal CA1 area before and after IRI. Collectively, in this experiment, pretreatment with aucubin protected CA1 pyramidal cells from forebrain IRI by attenuating oxidative stress and increasing neurotrophic factors. Thus, pretreatment with aucubin can be a promising candidate for preventing brain IRI. Full article

(This article belongs to the Special Issue New Strategies in Preventing Inflammatory and/or Oxidative-Stress-Induced Damages in Ischemia–Reperfusion Injury)

► Show Figures

Figure 1

Review

Jump to: Research, Other

20 pages, 1978 KiB

Open AccessReview

The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect

by Siyuan Yao, Aanchal Kasargod, Richard Chiu, Taylor R. Torgerson, Jerzy W. Kupiec-Weglinski and Kenneth J. Dery

Antioxidants 2024, 13(6), 678; https://doi.org/10.3390/antiox13060678 (registering DOI) - 31 May 2024

Abstract

Imbalances in the redox state of the liver arise during metabolic processes, inflammatory injuries, and proliferative liver disorders. Acute exposure to intracellular reactive oxygen species (ROS) results from high levels of oxidative stress (OxS) that occur in response to hepatic ischemia/reperfusion injury (IRI) and metabolic diseases of the liver. Antisense oligonucleotides (ASOs) are an emerging class of gene expression modulators that target RNA molecules by Watson–Crick binding specificity, leading to RNA degradation, splicing modulation, and/or translation interference. Here, we review ASO inhibitor/activator strategies to modulate transcription and translation that control the expression of enzymes, transcription factors, and intracellular sensors of DNA damage. Several small-interfering RNA (siRNA) drugs with N-acetyl galactosamine moieties for the liver have recently been approved. Preclinical studies using short-activating RNAs (saRNAs), phosphorodiamidate morpholino oligomers (PMOs), and locked nucleic acids (LNAs) are at the forefront of proof-in-concept therapeutics. Future research targeting intracellular OxS-related pathways in the liver may help realize the promise of precision medicine, revolutionizing the customary approach to caring for and treating individuals afflicted with liver-specific conditions. Full article

(This article belongs to the Special Issue New Strategies in Preventing Inflammatory and/or Oxidative-Stress-Induced Damages in Ischemia–Reperfusion Injury)

► Show Figures

Figure 1

19 pages, 4906 KiB

Open AccessReview

Hypoxic Inducible Factor Stabilization in Pericytes beyond Erythropoietin Production: The Good and the Bad

by Dario Troise, Barbara Infante, Silvia Mercuri, Claudia Piccoli, Bengt Lindholm and Giovanni Stallone

Antioxidants 2024, 13(5), 537; https://doi.org/10.3390/antiox13050537 - 27 Apr 2024

Viewed by 690

Abstract

The paracrine signaling pathways for the crosstalk between pericytes and endothelial cells are essential for the coordination of cell responses to challenges such as hypoxia in both healthy individuals and pathological conditions. Ischemia–reperfusion injury (IRI), one of the causes of cellular dysfunction and death, is associated with increased expression of genes involved in cellular adaptation to a hypoxic environment. Hypoxic inducible factors (HIFs) have a central role in the response to processes initiated by IRI not only linked to erythropoietin production but also because of their participation in inflammation, angiogenesis, metabolic adaptation, and fibrosis. While pericytes have an essential physiological function in erythropoietin production, a lesser-known role of HIF stabilization during IRI is that pericytes’ HIF expression could influence vascular remodeling, cell loss and organ fibrosis. Better knowledge of mechanisms that control functions and consequences of HIF stabilization in pericytes beyond erythropoietin production is advisable for the development of therapeutic strategies to influence disease progression and improve treatments. Thus, in this review, we discuss the dual roles—for good or bad—of HIF stabilization during IRI, focusing on pericytes, and consequences in particular for the kidneys. Full article

(This article belongs to the Special Issue New Strategies in Preventing Inflammatory and/or Oxidative-Stress-Induced Damages in Ischemia–Reperfusion Injury)

► Show Figures

Figure 1

31 pages, 2839 KiB

Open AccessReview

Inflammation in Myocardial Ischemia/Reperfusion Injury: Underlying Mechanisms and Therapeutic Potential

by Jamie Francisco and Dominic P. Del Re

Antioxidants 2023, 12(11), 1944; https://doi.org/10.3390/antiox12111944 - 31 Oct 2023

Cited by 8 | Viewed by 2573

Abstract

Acute myocardial infarction (MI) occurs when blood flow to the myocardium is restricted, leading to cardiac damage and massive loss of viable cardiomyocytes. Timely restoration of coronary flow is considered the gold standard treatment for MI patients and limits infarct size; however, this intervention, known as reperfusion, initiates a complex pathological process that somewhat paradoxically also contributes to cardiac injury. Despite being a sterile environment, ischemia/reperfusion (I/R) injury triggers inflammation, which contributes to infarct expansion and subsequent cardiac remodeling and wound healing. The immune response is comprised of subsets of both myeloid and lymphoid-derived cells that act in concert to modulate the pathogenesis and resolution of I/R injury. Multiple mechanisms, including altered metabolic status, regulate immune cell activation and function in the setting of acute MI, yet our understanding remains incomplete. While numerous studies demonstrated cardiac benefit following strategies that target inflammation in preclinical models, therapeutic attempts to mitigate I/R injury in patients were less successful. Therefore, further investigation leveraging emerging technologies is needed to better characterize this intricate inflammatory response and elucidate its influence on cardiac injury and the progression to heart failure. Full article

(This article belongs to the Special Issue New Strategies in Preventing Inflammatory and/or Oxidative-Stress-Induced Damages in Ischemia–Reperfusion Injury)

► Show Figures

Figure 1

Other

Jump to: Research, Review

22 pages, 5186 KiB

Open AccessSystematic Review

Perfusion Techniques in Kidney Allograft Preservation to Reduce Ischemic Reperfusion Injury: A Systematic Review and Meta-Analysis

by Bima J. Hasjim, Jes M. Sanders, Michael Alexander, Robert R. Redfield III and Hirohito Ichii

Antioxidants 2024, 13(6), 642; https://doi.org/10.3390/antiox13060642 - 24 May 2024

Viewed by 269

Abstract

The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included (n = 41 MP; n = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation. Full article

(This article belongs to the Special Issue New Strategies in Preventing Inflammatory and/or Oxidative-Stress-Induced Damages in Ischemia–Reperfusion Injury)

► Show Figures