Oxidative Stress and S100B Protein in Cirrhotic Children (original) (raw)
Related papers
Medicina
Background and objectives: Oxidative stress shows evidence of dysregulation in cirrhotic patients with hepatic encephalopathy (HE), although there are still controversies regarding the connections between oxidative stress and ammonia in these patients. The aim of this study was to evaluate the oxidative stress implication in overt HE pathogenesis of cirrhotic patients. Materials and Methods: We performed a prospective case-control study, which included 40 patients divided into two groups: group A consisted of 20 cirrhotic patients with HE and increased systemic ammoniemia, and group B consisted of 20 cirrhotic patients with HE and normal systemic ammoniemia. The control group consisted of 21 healthy subjects matched by age and sex. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) levels (lipid peroxidation marker), and ammoniemia were evaluated. Results: We found a significant decrease in SOD and GPx activity and also a significant incr...
Superoxide dismutase activity in children with chronic liver diseases
Journal of Hepatology, 2000
Background/Aims: Liver disease in infancy has multiple etiologies. As reactive oxygen interm~at~ are involved in several types of tissue damage, we have investigated whether different forms of liver disease in infancy are associated with increased free radical generation, using an indirect approach in which superoxide dismutase (a free radical scavenger) activity is determined in the liver tissue. methods: A total of 48 liver biopsies performed at diagnosis were evaluated retrospectively. Nine infants had biiary atresia, eight Alagille syndrome, seven alantitrypsin deficiency and 12 cryptogenic hepatitis. As controls we studied 12 biopsies with normal histology obtained from seven children with portal vein thrombosis and five children who underwent biopsy for management reason but had no liver disease. Superoxide dismutase activity in liver biopsy specimens was measured using the cytocbrome C method by spectrophotometry and expressed as U SODlmg protein. Rest&s: Superoxide dismuta~ activity was significantly increased in biliary atresia (1.25-C0.56 U IVER DISEASE in infancy has multiple etiologies, re-L sulting in a heterogeneous set of insults: infection, metabolic abnormality and anatomic anomalies (l-5). There is a considerable overlap between disorders involving the hepatocyte or the biliary apparatus in both clinical features and initial and subsequent sites of injury (6). Whether different mechanisms of tissue damage are involved in the different diagnostic categories remains to be clarified. In recent years, there has been increasing interest in the possible involvement of reactive oxygen intermediates (ROI) as pathogens in general and in the pathophysiology of liver injury in par
Oxidant stress is a significant feature of primary biliary cirrhosis
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2003
Primary biliary cirrhosis (PBC) is a chronic cholestatic disorder characterised by an immunological, and often granulomatous, attack on bile ducts leading to fibrosis, cirrhosis, liver failure and death. Animal and human studies suggest that oxidant stress plays a key role in progression of other liver diseases, but no comprehensive investigation has been performed previously in PBC. A wide range of lipid peroxidation and antioxidant markers were measured in the blood and urine of 41 patients with histologically confirmed PBC. Lipid peroxidation markers were significantly elevated [plasma and urinary 8-isoprostane, P < 0.001; plasma malondialdehyde (MDA), P = 0.007] compared to age-and sex-matched controls. The most striking antioxidant depletion occurred with plasma total glutathione where levels were significantly reduced (30% of controls). Total serum antioxidant levels were decreased (P = 0.013) and serum selenium and vitamin A were also lower (both P < 0.001); vitamins C and E were normal. Most patients had early disease biochemically and were Child-Pugh grade A. Urinary 8-isoprostane correlated positively with Ludwig stage and markers of hepatic injury and cholestasis. This study clearly demonstrates that oxidant stress, as reflected in a comprehensive spectrum of lipid peroxidation and antioxidant markers, is a significant feature of earlystage PBC. D
IMBALANCE OF OXIDANTS AND ANTIOXIDANT SYSTEMS IN SUBJECTS WITH CIRRHOSIS
Oxidative stress has been increasingly implicated in the pathogenesis of cirrhosis. Ethanol and various viral infections will increase the production of reactive oxygen species (ROS) in the liver, resulting in an imbalance between oxidants and antioxidants. Thus determination of oxidants along with antioxidants,stated the role of oxidative stress more accurately in the pathogenesis of liver cirrhosis. In the present study we measured the markers of prooxidants, erythrocyte malondialdehyde (MAD), antioxidants that included erythrocyte catalase, reduced glutathione (GSH), glutathione peroxidase (GPx). 30 subjects with age 25-60 years, who were diagnosed as having liver cirrhosis by the department of Gastroenterology, Narayana Medical Hospital were included, 30 normal healthy individuals of the same age were selected as control . The results clearly indicated that the levels of pro oxidants, MDA were high in cirrhotic subjects than in the controls with p value of 0.0001. The levels of antioxidant enzymes GSH, Catalase were low in cirrhosis with p value of 0.0001 (GSH) and 0.067(Catalase). But the mean value of glutathione peroxidase was high in cirrhosis than in controls. This may be due to conterregulation with oxidative stress. Hence this study indicates the role of oxidative stress in liver cirrhosis and it clearly defines the imbalance between oxidants & antioxidants.
Neurochemical Research, 2007
Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria. Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation, nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat braincerebral cortex, cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels, reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease in GSH/ GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced effects on pons medulla and cerebral cortex.
Free Radical Biology and Medicine, 2012
Chronic liver failure leads to hyperammonemia, a central component in the pathogenesis of hepatic encephalopathy (HE); however, a correlation between blood ammonia levels and HE severity remains controversial. It is believed oxidative stress plays a role in modulating the effects of hyperammonemia. This study aimed to determine the relationship between chronic hyperammonemia, oxidative stress, and brain edema (BE) in two rat models of HE: portacaval anastomosis (PCA) and bile-duct ligation (BDL). Ammonia and reactive oxygen species (ROS) levels, BE, oxidant and antioxidant enzyme activities, as well as lipid peroxidation were assessed both systemically and centrally in these two different animal models. Then, the effects of allopurinol (xanthine oxidase inhibitor, 100 mg/kg for 10 days) on ROS and BE and the temporal resolution of ammonia, ROS, and BE were evaluated only in BDL rats. Similar arterial and cerebrospinal fluid ammonia levels were found in PCA and BDL rats, both significantly higher compared to their respective sham-operated controls (p b 0.05). BE was detected in BDL rats (p b 0.05) but not in PCA rats. Evidence of oxidative stress was found systemically but not centrally in BDL rats: increased levels of ROS, increased activity of xanthine oxidase (oxidant enzyme), enhanced oxidative modifications on lipids, as well as decreased antioxidant defense. In PCA rats, a preserved oxidant/antioxidant balance was demonstrated. Treatment with allopurinol in BDL rats attenuated both ROS and BE, suggesting systemic oxidative stress is implicated in the pathogenesis of BE. Analysis of ROS and ammonia temporal resolution in the plasma of BDL rats suggests systemic oxidative stress might be an important "first hit", which, followed by increases in ammonia, leads to BE in chronic liver failure. In conclusion, chronic hyperammonemia and oxidative stress in combination lead to the onset of BE in rats with chronic liver failure.
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.
The role of oxidants and antioxidative parameters in patients with hepatic encephalopathy
International Journal of Scientific Reports, 2021
Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome present in patients with acute or chronic liver disease. 1 There is consensus that ammonia is a key toxin in HE, which may sensitize the brain to the different precipitating factors. 2 The term oxidative stress refers to a condition in which cells are subjected to ABSTRACT Background: Hepatic encephalopathy is a serious neuropsychiatric complication of cirrhosis. Changes in the oxidative and anti-oxidative system and nitric oxide levels in brain tissue contribute to the development of symptoms related to HE and HE. Purpose of the study to reveal the alterations in oxidative, anti-oxidative system and nitric oxide levels in cirrhotic patients during and after hepatic encephalopathy periods. Methods: This was a randomized controlled double-blind study conducted in Erciyes University Hospital between 3 July 2010 and 30 March 2011. We investigated the oxidative and anti-oxidative stress parameters by quantification of total antioxidant capacity (TAC), total oxidant capacity (TOC), nitric oxide (NO), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total thiol and xanthine oxidase (XO) levels in serum. We compared the group of patients with hepatic encephalopathy, post-hepatic encephalopathy (clinically recovered) and control groups (healthy control). Results: Thirty hepatic encephalopathy patients were studied. Serum levels of nitric oxide and xanthine oxidase were statistically significantly high in the hepatic encephalopathy group according to control group (p<0.031, and p<0.001, respectively). Serum thiol levels were significantly low in hepatic encephalopathy patients than the controls (p<0.001). Total oxidant capacity, total antioxidant capacity, glutathione peroxidase and superoxide dismutase levels were not significantly different in hepatic encephalopathy group than the controls. Serum thiol levels were low and serum NO levels were high in recovered clinically from hepatic encephalopathy group according to control group currently (p<0.001, p<0.001, respectively). Total antioxidant capacity, total oxidant capacity, glutathione peroxidase, superoxide dismutase and xanthine oxidase levels were similar in both groups (p>0.05). Total antioxidant capacity and especially xanthine oxidase levels were significantly decreased in recovered clinically from hepatic encephalopathy group compared to hepatic encephalopathy group (p<0.05, p<0.001, respectively). Conclusions: Oxidative system, in systemic circulation, is activated during hepatic encephalopathy and changes in XO level during and after hepatic encephalopathy is very different. This parameter may be a potential marker in differential diagnosis of hepatic encephalopathy from other coma causes. Further investigation is needed.