The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: A review

Abstract

Oxidative stress is an important factor in many pathological conditions such as inflammation, cancer, ageing and organ response to ischemia-reperfusion. Humans have developed a complex antioxidant system to eliminate or attenuate oxidative stress. Liver ischemia-reperfusion injury occurs in a number of clinical settings, including liver surgery, transplantation, and hemorrhagic shock with subsequent fluid resuscitation, leading to significant morbidity and mortality. It is characterized by significant oxidative stress but accompanied with depletion of endogenous antioxidants. This review has 2 aims: firstly, to highlight the clinical significance of liver ischemia-reperfusion injury, the underlying mechanisms and the main pathways by which the antioxidants function, and secondly, to describe the new developments that are ongoing in antioxidant therapy and to present the experimental and clinical evidence about the role of antioxidants in modulating hepatic ischemia-reperfusion injury. (Liver

Protective effects ofHammada scopariaflavonoid-enriched fraction on liver injury induced by warm ischemia/reperfusion

“…The pathogenesis of hepatic IR injury has attracted increasing attention in recent research, and hepatic IR injury has been described to follow a two-phase time course consisting of an initial and a late phase (Glantzounis et al, 2005). The initial phase of injury (within the first 2 h after reperfusion) is characterized by oxidative stress, where the production and the release of ROS directly result in hepatocellular injury (He et al, 2006;Wu et al, 2009).…”

Antioxidant Effects of Xanthohumol and Functional Impact on Hepatic Ischemia−Reperfusion Injury

“…17 Therapeutic interventions by treatment with antioxidants or gene therapy using viral and nonviral vectors containing genes of endogenous antioxidants have been shown to improve hepatic tissue injury. 18,19 Along with ROS, the redoxsensitive transcription factor nuclear factor κB (NF-κB) has been reported to play a pivotal role in the ischemia/reperfusion (IR) model, leading to the expression of proinflammatory cytokines and cell adhesion molecules, resulting in neutrophil-mediated inflammation following tissue injury. 15,20,21 Interestingly, NF-κB inhibition was attributed to antioxidant and radical-scavenging approaches and has been claimed to reduce injury following hepatic IR.…”

“…19,22,23 Thus, an interdependency of oxidative stress and NF-κB activation with tissue injury in hepatic IR is generally accepted. 18,24,25 These data have prompted us to elucidate the role of 1 in a complex oxidative stress driven injury model. The aim of this study was to investigate the impact of the dietary flavonoid xanthohumol on the hepatic IRI and to understand the underlying molecular mechanisms.…”

Response to antioxidant therapy in liver ischemia-reperfusion injury

“…4 -6 Different studies have shown inducible nitric oxide synthase inhibition to be either beneficial or detrimental. 7 Furthermore, use of a selective inducible nitric oxide synthase inhibitor showed beneficial effects in experimental models with endotoxemia, 8,9 but not with liver I/R. 9 We have found (our unpublished data) that large amounts of nitric oxide are generated during the late phase of liver I/R injury and that the beneficial effects of N-acetylcysteine are associated with reduced levels of nitric oxide.…”