Superoxide dismutase activity in children with chronic liver diseases (original) (raw)
Related papers
Reactive oxygen species in the normal and acutely injured liver
Journal of Hepatology, 2011
Livers generate low levels of reactive oxygen species (ROS), especially superoxide, in mitochondria and hydrogen peroxide as normal function of various oxidases [1]. The large number of mitochondria and their capacity to leak electrons from complex I and III of the electron transport chain make them quantitatively the most important intracellular source of ROS [1]. ROS formation is dangerous for cells due to the presence of polyunsaturated fatty acids in cellular membranes, the substantial number of unprotected protein sulfhydryl groups and DNA bases. Therefore, cells had to develop sophisticated defense systems. Each liver cell expresses superoxide dismutases (SOD1 in the cytosol; SOD2 in mitochondria), glutathione peroxidases (cytosol and mitochondria), catalase (peroxisomes), thioredoxins (Trx1 in cytosol; Trx2 in mitochondria) and peroxiredoxins (Prx-I,-II,-VI in the cytosol; Prx-III,-V in mitochondria) [1] (Figure 1A). In addition, liver cells contain mM concentrations of glutathione in all cellular compartments, have radical chain-breaking antioxidants (vitamin E) in cell membranes and keep redox-active iron tightly bound to storage or transport proteins [1]. Because of this multi-layer defense system against ROS, liver cells and especially hepatocytes, have a substantial capacity to metabolize and effectively detoxify ROS and repair oxidant damage. Therefore, under realistic in vivo conditions, catastrophic free radical events such as lipid peroxidation are rarely the cause of cell death [2]. Instead, ROS generally cause disturbances of the cellular homeostasis and, if not effectively counteracted, this can lead to cell death.
Chemico-Biological Interactions, 1992
The potential toxicity of enhanced intracellular reactive oxygen formation was investigated in isolated perfused livers of male Fischer rats. The presence of the redox-cycling agent diquat in the perfusate (200/zM) increased the basal effiux of glutathione disulfide (GSSG) into bile (2.65 ~-0.26 nmol GSH-equivalents/min per g liver wt.) and perfusate (0.55 ± 0.15 nmol/min per g)-10-fold. Since no evidence was found for degradation of GSSG in the biliary tract of these animals, it could be estimated that diquat induced a constant 02-generation of approximately 1000 nmol/min per g liver wt for 1 h. Thus, reactive oxygen formation under these conditions was 1-2 orders of magnitude higher than under various pathophysiological conditions. Only minor liver injury (release of lactate dehydrogenase activity) was observed. To increase the susceptibility of the liver to the oxidant stress, animals were pretreated in vivo with 200 mg/kg body wt. phorone, which caused a 90% depletion of the hepatic glutathione content, 100 mg/kg ferrous sulfate, a combination of phorone and ferrous sulfate, or 40 mg/kg BCNU, which caused a 60% inhibition of hepatic GSSG reductase. Only the combined treatment of phorone + ferrous sulfate or BCNU caused a significant increase of the diquat-induced liver injury. Our results demonstrated an extremely high resistance of the liver against intracellular reactive oxygen formation (even with impaired detoxification systems) and can serve as reference for the evaluation of potential contributions of reactive oxygen to liver injury in various disease states.
Reactive oxygen and mechanisms of inflammatory liver injury
Journal of Gastroenterology and Hepatology, 2000
cytes. 11 Moreover, ischaemic cell damage can lead to an intracellular oxidant stress during reoxygenation generated by mitochondria and xanthine oxidase. 12 Although there is overwhelming evidence that reactive oxygen species (ROS) play a significant role in a number of liver diseases, the detailed mechanisms of reactive oxygen involvement are still controversial. Because of the diverse roles ROS may play, elucidating injury mechanisms will be critical for identification of therapeutic interventions. This review will discuss some of the important mechanisms of ROS-induced injury during inflammation of the liver. Lipid peroxidation One of the oldest and still popular hypotheses of reactive oxygen-induced cell injury is killing by lipid peroxidation (LPO).
Advances in Bioscience and Biotechnology, 2012
The advantages of measuring hepatic oxidative status in liver biopsy are that it helps in diagnosis of hepatic dysfunction, reflects the degree of deterioration in the liver tissues, and helps to determine the severity of hepatic injury. We aimed to study the oxidative stress state in children with chronic hepatitis by using indirect approach in which antioxidant enzymes such as glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) are determined in the liver tissue. The present study included 21 children and adolescents (12 males, 9 females) suffering from chronic hepatitis. Patients were selected from the Hepatology Clinic, New Children's Hospital, Cairo University from November 2006 till 2009 and compared with a group of 7 children who happened to have incidental normal liver biopsy. Children with chronic hepatitis had mean age 8.12 ± 1.15 years. It was further subdivided into 2 subgroups: chronic viral heaptitis (n = 13) and cryptogenic hepatitis (n = 8). GPX, SOD and CAT levels were measured in fresh liver tissue (cell free homogenates) using ELISA. In chronic hepatitis group; there was a significant increase in the hepatic GPX activity (38.59 ± 35.82 nmol/min/ml) as compared to the control group (10.62 ± 6.68 nmol/min/ml). Also a significant correlation was observed between SOD and both ALT (r = 0.87, p < 0.05) and AST (r = 0.74, p < 0.05). GPX correlated with ALT (r = 0.80, p < 0.05) level in the chronic viral hepatitis subgroup. Our findings suggest that oxidative stress could play a role in the pathogenesis of chronic hepatitis. These preliminary results are encouraging to conduct more extensive clinical studies combining antioxidant therapy with various treatments.
Reactive oxygen and ischemia/reperfusion injury of the liver
Chemico-Biological Interactions, 1991
Pharmacological experiments suggested that reactive oxygen species contribute to ischemia-reperfusion injury of the liver. Since there is no evidence that quantitatively sufficient amounts of reactive oxygen are generated intracellularly to overwhelm the strong antioxidant defense mechanisms in the liver and cause parenchymal cell injury, the role of reactive oxygen in the pathogenesis remains controversial. This paper reviews the data and conclusions obtained with pharmacological intervention studies in vivo, the sources of reactive oxygen in the liver as well as the growing evidence for the importance of liver macrophages (Kupffer cells) and infiltrating neutrophils in the pathogenesis. A comprehensive hypothesis is presenLed that focuses on the extracellular generation of reactive oxygen in the hepatic sinusoids, where Kupffer cell-derived reacti~ oxygen species seem to be involved in the initial vascular and parenchymal cell injury and indirectly also in the recruitment of neutrophils into the liver. Reactive oxygen species may also contribute to the subsequent neutrophil-dependent injury phase as one of the toxic mediators released by these inflammatory cells.
Oxidative Stress in Children Chronic Hepatitis
Romanian Journal of Pediatrics, 2017
Oxidative stress reduces the efficacy of the immune response effector mechanisms, making the cells more susceptible to apoptosis. In lymphoid cells, free radicals interfere with the response to antiviral treatment, causing resistance to therapy and favoring chronic infection. One of the factors responsible for oxidative stress in chronic infection with hepatitis B is the production of pro-inflammatory cytokines. On the other hand, studies show that C hepatitis virus can directly induce oxidative stress in hepatocytes. Chronic C hepatitis core gene expression was associated with elevated reactive oxygen species markers, decreased intracellular and/or mitochondrial glutation content and increased level of oxidized thioredoxin and lipid peroxidation products. Moreover, increased level of the malonyl-dialdehyde in serum of patients with hepatocarcinoma is suggesting that MDA can be a reliable marker of liver injury quantification. Reduction of the oxidative stress can be done using antioxidant medication (hepatoprotectives, ursodeoxycholic acid and vitamin A, C, E), this approach representing an important benefit for the patient.
The importance of redox state in liver damage
Annals of hepatology
Oxidative stress is a major pathogenetic event occurring in several liver disorders ranging from metabolic to proliferative ones, and is a major cause of liver damage due to Ischemia/Reperfusion (I/R) during liver transplantation. The main sources of ROS are represented by mitochondria and cytocrome P450 enzymes in the hepatocyte, by Kupffer cells and by neutrophils. Cells are provided with efficient molecular strategies to strictly control the intracellular ROS level and to maintain the balance between oxidant and antioxidant molecules. A cellular oxidative stress condition is determined by an imbalance between the generation of ROS and the antioxidant defense capacity of the cell and can affect major cellular components including lipids, proteins and DNA. Proteins are very important signposts of cellular redox status and through their structure/function modulation, ROS can also influence gene expression profile by affecting intracellular signal transduction pathways. While several...