Résumés acceptés à l'AASLD et SFRBM2008

Résumés acceptés

Félicitations à toute l'équipe pour les 2 résumés qui ont été acceptés à deux grandes conférences internationales, une portant sur les maladies hépatiques et l'autre sur le stress oxydatif!

Notre résumé sera présenté par Cristina Bosoi à l'AASLD (American Association for the study of liver diseases) qui aura lieu du 31 octobre au 4 novembre 2008 à San Francisco. Elle assistera à une conférence sur le stress oxydatif, le SFRBM, du 19-23 novembre, à Indianapolis, États-Unis.

Publications connexes

Hyperammonemia does not induce oxidative/nitrosative stress in rats with portacaval anastomosis.

Cristina Bosoi, Mélanie Tremblay, Christopher F. Rose.

Background: Ammonia is central in the pathogenesis of hepatic encephalopathy however it is believed systemic oxidative/nitrosative stress may play an important role in exacerbating the neuropsychological effects of hyperammonemia observed in patients with cirrhosis. Furthermore, it has recently been demonstrated in vitro that pathophysiological concentrations of ammonia induce oxidative/nitrosative stress in brain (cultured astrocytes), however this remains to be evaluated in vivo. The present study aims to investigate the role of oxidative/nitrosative stress in a well characterized hyperammonemic rat model of portacaval anastomosis (PCA). Methods: Rats were sacrificed 4 weeks following PCA or SHAM-operation. Ammonia, nitrate/nitrite, reactive oxygen species and total glutathione were measured in both plasma (arterial) and cerebrospinal fluid. Activities of antioxidant enzymes (catalase, superoxide dismutase and glutathione reductase/peroxidase) were measured in both plasma (arterial) and frontal cortex of the brain. Results: Ammonia concentrations were increased in both plasma (PCA: 173.7 ± 13.58uM vs SHAM: 77.8 ± 11.2uM; p<0.001) and cerebrospinal fluid (PCA: 146.6 ± 26.0uM vs SHAM: 31.5 ± 6.9uM; p<0.001) in PCA rats compared to SHAM operated controls. Furthermore, PCA rats showed a significant increase in catalase (PCA: 3.27 ± 0.03U/ml vs SHAM: 3.10 ± 0.05U/ml; p<0.05) and superoxide dismutase (PCA: 97.30 ± 0.47 vs SHAM: 95.57 ± 0.45 % inhibition; p<0.05) activities, but no significant differences were found in frontal cortex between the two groups. In addition, no significant changes in reactive oxygen species, nitrate/nitrite and total glutathione levels, nor in glutathione reductase and peroxidase activities were found in both plasma and brain tissue of PCA and SHAM rats. Conclusion: Rats with PCA develop hyperammonemia which leads to toxic levels of ammonia in the brain. This in turn does not induce oxidative/nitrosative stress systemically or centrally. Maintenance of systemic antioxidant activity in rats with PCA preserves a balanced redox status and prevents progression of encephalopathy.

Synergistic effect of systemic oxidative stress and hyperammonemia leads to brain edema in rats with chronic liver failure.

Cristina R. Bosoi, Christian Parent-Robitaille, Mélanie Tremblay, Christopher F. Rose.

Background: Liver failure/disease leads to hyperammonemia which is central in the pathogenesis of hepatic encephalopathy. However, it is believed systemic oxidative/nitrosative stress may play an important role in exacerbating the neuropsychological effects of hyperammonemia observed in patients with liver disease. The present study aims to investigate the role of oxidative/nitrosative stress in 2 rat models of liver disease/hepatic encephalopathy; 1) portacaval anastomosis (PCA), and 2) bile-duct ligation (BDL). Methods: Rats were sacrificed 4 weeks following PCA or 6 weeks following BDL. Ammonia, reactive oxygen species (ROS), H2O2 and nitric oxide (NO) were measured in plasma (arterial) and ammonia, ROS and NO were measured in cerebrospinal fluid (CSF) using respectively a commercially available kit, a fluorescent technique and the Griess reaction. Brain water was measured in the frontal cortex using a specific gravimetric technique. Results: Hyperammonemia developed in both PCA (PCA: 173.7 ± 13.6 uM vs sham: 77.8 ± 11.2 uM; p<0.001) and BDL (BDL: 114.1 ± 19.2 uM vs sham: 33.2 ± 4.7 uM; p<0.05) rats with PCA rats being significantly higher compared to BDL rats (p<0.05). Consequently, ammonia increased in CSF in both PCA (PCA: 146.6 ± 26.0 uM vs sham: 31.5 ± 6.9 uM; p<0.001) and BDL (BDL: 128.4 ± 36.7 uM vs sham: 23.3 ± 6.1 uM; p<0.05). No significant change was observed between PCA and BDL. Only rats with BDL demonstrated an increase in plasma levels of ROS (5.8-fold increase vs sham; p<0.001) and H2O2 (3.2-fold increase vs sham; p<0.05). No significant change in CSF ROS was found in BDL or PCA compared to their respective control groups. In addition, an increase in brain water content was only observed in rats with BDL (BDL: 81.52 ± 0.15% vs sham: 80.43 ± 0.21%, p<0.05). No significant change in plasma ROS, H2O2 or brain water was found in PCA rats vs sham-operated controls. Conclusion: Oxidative stress in addition to hyperammonemia results in an increase in brain water in rats with BDL which is not in PCA rats where only hyperammonemia is observed. Our findings suggest systemic oxidative stress is implicated in the pathogenesis of brain edema and its synergistic effect with ammonia may lead to progression of hepatic encephalopathy.