The Current State of Knowledge of Hepatic Ischemia-Reperfusion Injury Based on Its Study in Experimental Models

Mendes‐Braz, Mariana; Elias-Miró, M.; Jiménez‐Castro, Mónica B.; Casillas-Ramírez, Araní; Ramalho, Fernando Silva; Peralta, Carmen

doi:10.1155/2012/298657

Cited by 135 publications

(118 citation statements)

References 122 publications

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“…Lipid peroxidation itself produces toxic substances, including MDA. Furthermore, in addition to directly damaging the structure of cells (19), hypoxia can induce disturbances in hepatic microcirculation, leading to further ischemia and anoxic liver damage (20). MT consists of both hydrophilic and hydrophobic moieties, and is synthesized by the PG, which exists in all vertebrates.…”

Section: Discussionmentioning

confidence: 99%

Effects of melatonin on liver function and lipid peroxidation in a rat model of hepatic ischemia/reperfusion injury

Deng

Liu

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to investigate the effects of melatonin (MT) on liver function and lipid peroxidation following hepatic ischemia-reperfusion injury (IRI). A total of 66 male Sprague-Dawley rats were randomly assigned into three groups: Normal control (N) group, ischemia-reperfusion (IR) group and the MT-treated group. A hepatic IRI model was developed by blocking the first porta hepatis, and subsequently restoring hepatic blood inflow after 35 min. Following reperfusion, changes in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were detected by a chemical method at various time points. In the MT group, the MDA levels were significantly reduced (P<0.05) at all time points, as compared with the IR group. Furthermore, SOD activity was significantly increased (P<0.05) in the MT group, as compared with the IR group at all time points; and the levels of GSH in the MT group were significantly higher (P<0.05) than those of the IR group at 2, 4, and 8 h post-reperfusion. The levels of ALT, AST and LDH were significantly reduced in the MT group at each time point, as compared with that of the IR group (P<0.05). In conclusion, MT exhibits potent antioxidant properties that may create favorable conditions for the recovery of liver function following IRI. IntroductionIn order to effectively control bleeding during hepatobiliary surgery, hepatic portal occlusion is often used, as it can temporarily interrupt the portal vein and hepatic artery inflow. This method is widely accepted since it is clinically simple, practical and effective; however, there is an inherent risk of subsequent liver ischemia-reperfusion injury (IRI). Therefore, in recent years, clinical research in the field of hepatic surgery has focused on how to reduce blood loss and improve the safety of hepatic portal occlusion, whilst simultaneously reducing the risk of liver IRI.Previous studies investigating tissues and organs such as the brain, heart, kidney and retina have demonstrated that numerous free radicals are produced during IRI, when the endogenous radical scavengers cannot function appropriately, leading to cell damage (1,2). Therefore, investigating effective drugs that alleviate IRI-induced functional liver damage, and improve the postoperative survival rate, has become a research hotspot in the field of hepatic surgery. Melatonin (MT) is a neural endocrine hormone that is secreted by the pineal gland (PG), which exerts known antioxidant, antitoxic, anti-stress and anti-inflammatory effects (3,4). Previous studies have demonstrated that MT has a protective role in IRI of the brain, heart, kidney and retina (5); however, its protective effects in liver IRI and the underlying mechanism require further research. An animal model of hepatic portal occlusion was used in the present study. MT was administered in advance, and the influence and significance of MT on antioxidant capacity, lipid peroxidation ...

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Section: Discussionmentioning

confidence: 99%

Effects of melatonin on liver function and lipid peroxidation in a rat model of hepatic ischemia/reperfusion injury

Deng

Liu

et al. 2016

Experimental and Therapeutic Medicine

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“…37 In addition, another study reports that I/R injury is associated with a reduction in sinusoid density within the liver, 39 which is believed to impair hepatic microcirculation. 40 Therefore delayed fluorescein uptake may be due to a decrease in sinusoid diameter that impairs blood flow and thus availability of the dye to the hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury

et al. 2013

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Abstract. The liver is important in the biotransformation of various drugs, where hepatic transporters facilitate uptake and excretion. Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery, and the developing oxidative stress can lead to graft failure. We used intravital multiphoton tomography, with fluorescence lifetime imaging, to characterize metabolic damage associated with hepatic I/R injury and to model the distribution of fluorescein as a measure of liver function. In addition to measuring a significant increase in serum alanine transaminase levels, characteristic of hepatic I/R injury, a decrease in the averaged weighted lifetime of reduced nicotinamide adenine dinucleotide phosphate was observed, which can be attributed to a changed metabolic redox state of the hepatocytes. I/R injury was associated with delayed uptake and excretion of fluorescein and elevated area-under-the-curve within the hepatocytes compared to sham (i.e., untreated control) as visualized and modeled using images recorded by intravital multiphoton tomography. High-performance liquid chromatography analysis showed no differences in plasma or bile concentrations of fluorescein. Finally, altered fluorescein distribution was associated with acute changes in the expression of liver transport proteins. In summary, multiphoton intravital imaging is an effective approach to measure liver function and is more sensitive in contrasting the impact of I/R injury than measuring plasma and bile concentrations of fluorescein.

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“…Perfusion is important prior to liver transplantation, in which the solution acts to preserve the liver tissue and protect it from reperfusion injury. Reperfusion injury is a phenomenon that results from oxidative damage that occurs to the tissue when the blood supply returns to the liver after a period of ischemia (Mendes-Braz et al, 2012). Additives in the perfusion solution can mitigate the damage caused by these deleterious oxidative processes.…”

Section: Introductionmentioning

confidence: 99%

Why Do Most Human Liver Cytosol Preparations Lack Xanthine Oxidase Activity?

et al. 2014

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When investigating the potential for xanthine oxidase (XO)-mediated metabolism of a new chemical entity in vitro, selective chemical inhibition experiments are typically used. Most commonly, these inhibition experiments are performed using the inhibitor allopurinol (AP) and commercially prepared human liver cytosol (HLC) as the enzyme source. For reasons detailed herein, it is also a common practice to perfuse livers with solutions containing AP prior to liver harvest. The exposure to AP in HLC preparations could obviously pose a problem for measuring in vitro XO activity. To investigate this potential problem, an HPLC-MS/MS assay was developed to determine whether AP and its primary metabolite, oxypurinol, are retained within the cytosol for livers that were treated with AP during liver harvest. Differences in enzymatic activity for XO and aldehyde oxidase (AO) in human cytosol that can be ascribed to AP exposure were also evaluated. The results confirmed the presence of residual AP (some) and oxypurinol (all) human liver cytosol preparations that had been perfused with an AP-containing solution. In every case where oxypurinol was detected, XO activity was not observed. In contrast, the presence of AP and oxypurinol did not appear to have an impact on AO activity. Pooled HLC that was purchased from a commercial source also contained residual oxypurinol and did not show any XO activity. In the future, it is recommended that each HLC batch is screened for oxypurinol and/or XO activity prior to testing for XO-mediated metabolism of a new chemical entity.

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The Current State of Knowledge of Hepatic Ischemia-Reperfusion Injury Based on Its Study in Experimental Models

Cited by 135 publications

References 122 publications

Effects of melatonin on liver function and lipid peroxidation in a rat model of hepatic ischemia/reperfusion injury

Effects of melatonin on liver function and lipid peroxidation in a rat model of hepatic ischemia/reperfusion injury

Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury

Why Do Most Human Liver Cytosol Preparations Lack Xanthine Oxidase Activity?

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