Abstract
Thiol-containing compounds have an essential role in many biochemical reactions due to their ability to be easily oxidised and then quickly regenerated. Main representatives are glutathione, lipoic acid and thioredoxin which are synthesised de novo in mammalian cells. N-acetylcysteine and Bucillamine are synthetic thiols which have been administered in experimental and clinical studies for treatment of conditions associated with oxidative stress. Ischemia and reperfusion (I/R) injury is characterised by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. I/R occurs in a variety of clinical settings such as liver resection, organ transplantation, haemorrhagic shock with fluid resuscitation, heart surgery, myocardial infarction followed by reperfusion and laparoscopic surgery. In these circumstances, the administration of antioxidant agents such as thiols, could provide protection from the harmful effects of I/R injury. However, the ability of thiol compounds to reduce free radicals is associated with the formation of thiyl radicals and the rate and efficiency of removal of thiyl radicals has a critical effect on antioxidant or prooxidant actions of thiols in the cells. The aim of this review is to present the mechanisms by which thiols act as antioxidants and signalling molecules and the experimental and clinical evidence regarding their role in I/R injury with a particular emphasis on liver I/R. The current evidence suggests that thiols ameliorate I/R injury and that their clinical significance should be further evaluated in large scale randomised clinical trials.
Keywords: Thiols, ischemia / reperfusion, reactive oxygen species, liver, oxidative stress, Glutathione, N-acetylcysteine, Bucillamine
Current Pharmaceutical Design
Title: The Role of Thiols in Liver Ischemia-Reperfusion Injury
Volume: 12 Issue: 23
Author(s): George K. Glantzounis, Wenxuan Yang, Rahul S. Koti, Dimitri P. Mikhailidis, Alexander M. Seifalian and Brian R. Davidson
Affiliation:
Keywords: Thiols, ischemia / reperfusion, reactive oxygen species, liver, oxidative stress, Glutathione, N-acetylcysteine, Bucillamine
Abstract: Thiol-containing compounds have an essential role in many biochemical reactions due to their ability to be easily oxidised and then quickly regenerated. Main representatives are glutathione, lipoic acid and thioredoxin which are synthesised de novo in mammalian cells. N-acetylcysteine and Bucillamine are synthetic thiols which have been administered in experimental and clinical studies for treatment of conditions associated with oxidative stress. Ischemia and reperfusion (I/R) injury is characterised by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. I/R occurs in a variety of clinical settings such as liver resection, organ transplantation, haemorrhagic shock with fluid resuscitation, heart surgery, myocardial infarction followed by reperfusion and laparoscopic surgery. In these circumstances, the administration of antioxidant agents such as thiols, could provide protection from the harmful effects of I/R injury. However, the ability of thiol compounds to reduce free radicals is associated with the formation of thiyl radicals and the rate and efficiency of removal of thiyl radicals has a critical effect on antioxidant or prooxidant actions of thiols in the cells. The aim of this review is to present the mechanisms by which thiols act as antioxidants and signalling molecules and the experimental and clinical evidence regarding their role in I/R injury with a particular emphasis on liver I/R. The current evidence suggests that thiols ameliorate I/R injury and that their clinical significance should be further evaluated in large scale randomised clinical trials.
Export Options
About this article
Cite this article as:
Glantzounis K. George, Yang Wenxuan, Koti S. Rahul, Mikhailidis P. Dimitri, Seifalian M. Alexander and Davidson R. Brian, The Role of Thiols in Liver Ischemia-Reperfusion Injury, Current Pharmaceutical Design 2006; 12 (23) . https://dx.doi.org/10.2174/138161206777947641
DOI https://dx.doi.org/10.2174/138161206777947641 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Conjugates of Natural Compounds with Nitroxyl Radicals as a Basis for Creation of Pharmacological Agents of New Generation
Current Medicinal Chemistry Small Molecule Antagonists of the CXCR2 and CXCR1 Chemokine Receptors as Therapeutic Agents for the Treatment of Inflammatory Diseases
Current Topics in Medicinal Chemistry Preventing Vascular Graft Failure: Endothelial Cell Seeding and Tissue Engineering
Vascular Disease Prevention (Discontinued) Reactive Oxygen Species, Nitric Oxide and Hypertensive Endothelial Dysfunction
Current Hypertension Reviews Flavonoids Isolated from Rumex aquaticus Exhibit Neuroprotective and Neurorestorative Properties by Enhancing Neurite Outgrowth and Synaptophysin
CNS & Neurological Disorders - Drug Targets The Effects of Sevoflurane or Remifentanil on the Stress Response to Surgical Stimulus
Current Pharmaceutical Design Cardiolipin Metabolism and the Role it Plays in Heart Failure and Mitochondrial Supercomplex Formation
Cardiovascular & Hematological Disorders-Drug Targets Biological Properties and Therapeutic Potential of Bilirubin
Mini-Reviews in Medicinal Chemistry The Role of Oxidative Stress on Necrotizing Enterocolitis in Very Low Birth Weight Infants
Current Pediatric Reviews Design, Synthesis and Biological Study of Novel NO-Donor-Caffeic Acid Hybrids as Potential Anti-Atherosclerotic Drug Candidates
Letters in Drug Design & Discovery The Possibility of Novel Antiplatelet Peptides: The Physiological Effects of Low Molecular Weight HSPs on Platelets
Current Pharmaceutical Design Cardiovascular Effects of Modulators of Soluble Guanylyl Cyclase Activity
Cardiovascular & Hematological Agents in Medicinal Chemistry Stem Cell and Tissue Engineering Therapies for Ocular Regeneration
Current Stem Cell Research & Therapy The Use of Ghrelin and Ghrelin Receptor Agonists as a Treatment for Animal Models of Disease: Efficacy and Mechanism
Current Pharmaceutical Design Potential of Resveratrol in Preventing the Development of Heart Failure
Current Chemical Biology Molecular Targets of FTY720 (Fingolimod)
Current Molecular Medicine Agonists of the Tissue-Protective Erythropoietin Receptor in the Treatment of Parkinson’s Disease
Current Topics in Medicinal Chemistry Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases
Current Medicinal Chemistry Stem Cell Therapy for Ischaemic Stroke: Translation from Preclinical Studies to Clinical Treatment
CNS & Neurological Disorders - Drug Targets Damage-Associated Molecular Patterns – Emerging Targets for Biologic Therapy of Childhood Arthritides
Inflammation & Allergy - Drug Targets (Discontinued)