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.
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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 |
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