Brain Oxidative Stress Induced by Obstructive Jaundice in Rats

Neurochemical Research, 2008

The study aimed to directly measure in vivo superoxide radical (O 2 -) a direct indicator of oxidative stress, in the brain of rats with experimentally induced obstructive jaundice by employing a new quantitative ultrasensitive fluorescent assay requiring minimum sample. O 2 anion is specific for dihydroethidine (DHE) and upon reaction gives a characteristic product, namely 2-OHethidium. Ten male rats underwent laparotomy and were divided into two groups: I, sham operated and II bile duct ligation. Ten days later, following injection with DHE (a O 2 trap), all animals were killed and samples from cerebral cortex, midbrain and cerebellum were removed for analysis. It was shown that compared to group I, in group II the O 2 was increased by 67% in the cerebral cortex and by 37% in the midbrain as a consequence of experimental obstructive jaundice, while its levels were unaffected in the cerebellum. The data in this experimental obstructive jaundice model imply a region-specific increase of O 2 -formation rate, being higher in cerebral cortex, less so in the midbrain and not at all in cerebellum.

Brain Research, 2006

We examined the possible protective effect of certain antioxidants (N-acetylcysteine, allopurinol and vitamin E) against the oxidative stress of brain tissue induced by experimental obstructive jaundice in rats. Thirty-six male Wistar rats were randomly divided into six groups; group I control, group II sham operated, group III bile duct ligated and groups IV, V, and VI in which the rats, after bile duct ligation, were given every day an intraperitoneal injection with N-acetylcysteine, allopurinol and Vit-E respectively. All rats were sacrificed on the tenth day by exsanguination and the oxidative state in samples from cortex, midbrain and cerebellum was assessed by measuring the thiol redox state and lipid peroxidation quantified by MDA measurements. The main finding was that all three antioxidants decrease lipid peroxidation in the three brain areas. Cysteine levels increased and protein thiol levels were reserved only in the group treated with N-acetylcysteine, whereas oxidized glutathione increased dramatically in the group treated with allopurinol, suggesting that each antioxidant agent had a certain influence profile on the different antioxidant defense systems. The observed effects of the antioxidants in this experimental model could also provide insight into some aspects of jaundice-induced hepatic encephalopathy in humans.

Redox Report, 2008

Oxidative stress seems to be a cardinal feature of cholestasis, implicated in the pathophysiology of organ injury not only in the liver, but also in several extrahepatic tissues. The present study was designed to assess directly oxidative stress in vital organs of experimentally jaundiced rats by measuring the key oxidative stress marker superoxide radical (O 2

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.

Free Radical Research, 2009

Transplantation Proceedings, 2005

The etiological mechanisms of brain edema in fulminant hepatic failure are incompletely understood. In a surgical model of fulminant hepatic failure in the rat, we tested whether oxidative stress may be involved in the early steps of brain edema. Moreover, we took advantage of this model to determine if oxidative stress may be involved in the hepatocyte dysfunction observed in the setting of fulminant hepatic failure. Oxidative stress was evaluated by measurement of tissue ascorbic acid in the brain and liver of rats at 6 hours after induction of fulminant hepatic failure versus in control or partially hepatectomized rats. After 6 hours, the level of ascorbic acid was not different in the brain tissue of the various groups, indicating no oxidative stress. The liver showed a significant decrease in ascorbic acid levels, both in ischemic and nonischemic liver tissue, suggesting that oxidative stress might be involved in the failure of liver regeneration in fulminant hepatic failure. In this rat model no oxidative stress was demonstrated in the brain during the early phase of fulminant liver failure.

Asian Journal of Surgery, 2015

Background/Objective: The study aims to evaluate the alterations in the brain due to oxidative stress and lipid peroxidation resulting from obstructive jaundice. Methods: Forty-one Wistar albino rats were used in this study. Simple laparotomy was performed in the sham group (n Z 5). In the remaining 36 rats, the common bile duct (CBD) was found and ligated. They were divided into six groups. Group I, Group II, and Group III were sacrificed at the 3 rd , 7 th , and 14 th day of ligation, respectively. In Group Id, Group IId, and Group IIId ligated bile ducts were decompressed at the 3 rd , 7 th , and 14 th day, respectively. One week after decompression these rats were also sacrificed and samples were taken. Results: After the CBD ligation, serum levels of bilirubin and malondialdehyde were found to be increased progressively in parallel to the ligation time of the CBD. After decompression these values decreased. In electron microscopy evaluation, the damage was found to be irreversible depending on the length of the obstruction period. In Group II, the damage was mostly reversible after the internal drainage period of 7 days. However in Group III, the tissue damage was found to be irreversible despite the decreased values of oxidative stress and bilirubin. Conclusion: Ultrastructural changes in brain tissue including damage in the glial cells and neurons, were found to be irreversible if the CBD ligation period was >7 days and did not

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.

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.