Preventive Effects of Superoxide Dismutase Derivatives Modified with Monosaccharides on Reperfusion Injury in Rat Liver Transplantation

Mizoe, Akihiko; Kondo, Satoshi; Azuma, Takashi; Fujioka, Hikaru; Tanaka, Keisei; Hashida, Mitsuru; Kanematsu, Takashi

doi:10.1006/jsre.1997.5215

Cited by 38 publications

(21 citation statements)

References 21 publications

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“…Since antioxidants can inhibit ROS, various studies have aimed at modulating the severity of IR damage utilizing different mechanisms, including pharmacological allopurinol [58,59], a-tocopherol [60], N-acethylcysteine [61], and enzymatic catalase [62,63] and SOD [57]. Endogenous antioxidant concentrations decrease significantly during reperfusion [60,64]; thus, administration of antioxidants, especially in the early stages of reperfusion, may significantly diminish IR injury in transplanted livers.…”

Section: Ischemia/reperfusion Liver Injury and Free Radicalsmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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Reactive oxygen and nitrogen species (ROS and RNS) are produced by metabolism of normal cells. However, in liver diseases, redox is increased thereby damaging the hepatic tissue; the capability of ethanol to increase both ROS/RNS and peroxidation of lipids, DNA, and proteins was demonstrated in a variety of systems, cells, and species, including humans. ROS/RNS can activate hepatic stellate cells, which are characterized by the enhanced production of extracellular matrix and accelerated proliferation. Cross-talk between parenchymal and nonparenchymal cells is one of the most important events in liver injury and fibrogenesis; ROS play an important role in fibrogenesis throughout increasing platelet-derived growth factor. Most hepatocellular carcinomas occur in cirrhotic livers, and the common mechanism for hepatocarcinogenesis is chronic inflammation associated with severe oxidative stress; other risk factors are dietary aflatoxin B 1 consumption, cigarette smoking, and heavy drinking. Ischemia-reperfusion injury affects directly on hepatocyte viability, particularly during transplantation and hepatic surgery; ischemia activates Kupffer cells which are the main source of ROS during the reperfusion period. The toxic action mechanism of paracetamol is focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-pbenzoquinone imine to cellular proteins as the main cause of hepatic cell death; intracellular steps critical for cell death include mitochondrial dysfunction and, importantly, the formation of ROS and peroxynitrite. Infection with hepatitis C is associated with increased levels of ROS/RNS and decreased antioxidant levels. As a consequence, antioxidants have been proposed as an adjunct therapy for various liver diseases.

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Section: Ischemia/reperfusion Liver Injury and Free Radicalsmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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“…OFR scavengers (32,33) and inhibitors (34), and delivery of antioxidant enzyme genes (35), minimized liver IRI. Adenovirus-mediated gene delivery of the cytosolic Cu/Zn superoxide dismutase gene in a rat marginal liver transplant model reduced OFR production and reduced liver injury (36).…”

Section: Ofrs and Scavengersmentioning

confidence: 99%

Molecular Mediators of Liver Ischemia and Reperfusion Injury: A Brief Review

Vardanian¹,

Busuttil²,

Kupiec‐Weglinski³

2008

Mol Med

139

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Ischemia and reperfusion injury is a dynamic process that involves multiple organ systems in various clinical states including transplantation, trauma, and surgery. Research into this field has identified key molecular and signaling players that mediate, modulate, or augment cellular, tissue, and organ injury during this disease process. Further elucidation of the molecular mechanisms should provide the rationale to identify much-needed novel therapeutic options to prevent or ameliorate organ damage due to ischemia and reperfusion in clinics.

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“…7,8 Kupffer cells and endothelial cells are thought to be sources of oxygen free radical generation in liver. [9][10][11][12] The protection of endothelial cells is essential to prevent damage due to ischaemia/reperfusion. 13 Tissue damage may result in lipid peroxidation and necrosis.…”

Section: Resultsmentioning

confidence: 99%

The protective mechanisms of defibrotide on liver ischaemia–reperfusion injury

Aydemir¹,

Var²,

Uyanık³

et al. 2003

Cell Biochemistry & Function

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During some surgical interventions, temporary occlusion of the hepatic blood supply may cause ischaemia-reperfusion (I/R) injury and hepatic dysfunction. In this study the protective effect of defibrotide (DEF) was evaluated in a rat model of liver I/R injury. Four groups of rats were subjected to the following protocols: saline infusion without ischaemia, DEF infusion without ischaemia, DEF infusion with hepatic I/R, and saline infusion with hepatic I/R. After a midline laporatomy, liver ischaemia was induced by 45 min of portal occlusion. DEF 175 mg/kg(-1) was infused before ischaemia in 10 ml of saline. The same volume of saline was infused into the control animals. At the end of the 45-min reperfusion interval, the animals were sacrified. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities were determined in haemolysates, and malondialdehyde (MDA) level in the liver tissue was measured. Tissue MDA levels were significantly higher in the I/R plus saline group compared to the sham operation control groups (p < 0.01 and p < 0.05, respectively). Tissue MDA levels decreased in the DEF plus I/R group compared to the I/R plus saline group (p < 0.05), but DEF could not reduce tissue lipid peroxidation to the levels of the control sham operation groups. SOD and GSH-Px enzyme activities were significantly higher in DEF-treated animals than in the other groups (p < 0.05). These results suggest that DEF protects liver against I/R injury by increasing the antioxidant enzyme levels.

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Preventive Effects of Superoxide Dismutase Derivatives Modified with Monosaccharides on Reperfusion Injury in Rat Liver Transplantation

Cited by 38 publications

References 21 publications

Role of free radicals in liver diseases

Role of free radicals in liver diseases

Molecular Mediators of Liver Ischemia and Reperfusion Injury: A Brief Review

The protective mechanisms of defibrotide on liver ischaemia–reperfusion injury

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