Document Detail

Induction of systemic oxidative stress leads to brain oedema in portacaval shunted rats.
MedLine Citation:
PMID:  25354203     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND & AIMS: The pathogenesis of hepatic encephalopathy (HE) is multifactorial and often associated with the development of brain oedema. In addition to ammonia playing a central role, systemic oxidative stress is believed to aggravate the neuropsychological effects of ammonia in patients with chronic liver disease (CLD). The aim of this study was to (i) induce systemic oxidative stress in hyperammonaemic portacaval anastomosed (PCA) rats by inhibiting the antioxidant glutathione using Dimethyl maleate (DEM) and (ii) investigate whether a synergistic relationship between ammonia and oxidative stress contributes to the pathogenesis of brain oedema in CLD.
METHODS: Four-week PCA and sham-operated rats received DEM (0.4-4 mg/kg/day) for the last 10 days before sacrifice when oxidative stress markers [reactive oxygen species (ROS) and malondialdehyde (MDA)] were assessed in blood and frontal cortex. Brain water content was measured using a specific gravimetric technique.
RESULTS: Dimethyl maleate induced an increase in ROS and MDA in the blood, but not in the brain, of the PCA rats, compared with non-treated PCA rats. This was accompanied with an increase in brain water content (PCA+DEM: 78.45 ± 0.13% vs. PCA: 77.38 ± 0.11%, P < 0.001). Higher doses of DEM induced systemic oxidative stress in sham-operated controls, but brain oedema did not develop.
CONCLUSIONS: Dimethyl maleate provoked systemic, not central, oxidative stress in PCA rats, resulting in the development of brain oedema. Independently, hyperammonaemia and systemic oxidative stress do not precipitate brain oedema; therefore, our findings sustain that a synergistic effect between hyperammonaemia and systemic oxidative stress is responsible for the development of brain oedema in HE.
Cristina R Bosoi; Mélanie Tremblay; Christopher F Rose
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Publication Detail:
Type:  Journal Article     Date:  2013-12-17
Journal Detail:
Title:  Liver international : official journal of the International Association for the Study of the Liver     Volume:  34     ISSN:  1478-3231     ISO Abbreviation:  Liver Int.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101160857     Medline TA:  Liver Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1322-9     Citation Subset:  IM    
Copyright Information:
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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