AST-120 (spherical carbon adsorbent) lowers ammonia levels and attenuates brain edema in bile duct-ligated rats
dc.contributor.author | Bosoi, Cristina R. | |
dc.contributor.author | Parent-Robitaille, Christian | |
dc.contributor.author | Anderson, Keith | |
dc.contributor.author | Tremblay, Mélanie | |
dc.contributor.author | Rose, Christopher | |
dc.date.accessioned | 2015-03-05T14:20:15Z | |
dc.date.available | 2015-03-05T14:20:15Z | |
dc.date.issued | 2011 | |
dc.identifier.uri | http://hdl.handle.net/1866/11395 | |
dc.subject | Ammonia | fr |
dc.subject | Chronic liver failure | fr |
dc.subject | Oxidative stress | fr |
dc.subject | Hepatic encephalopathy | fr |
dc.subject | Activated carbon microspheres | fr |
dc.subject | Ammoniac | fr |
dc.subject | Maladie du foie en phase terminale | fr |
dc.subject | Stress oxydatif | fr |
dc.subject | Encéphalopathie hépatique | fr |
dc.title | AST-120 (spherical carbon adsorbent) lowers ammonia levels and attenuates brain edema in bile duct-ligated rats | fr |
dc.type | Article | fr |
dc.contributor.affiliation | Université de Montréal. Faculté de médecine | fr |
dc.contributor.affiliation | Université de Montréal. Faculté de médecine. Centre de recherche du CHUM | fr |
dc.identifier.doi | 10.1002/hep.24273 | |
dcterms.abstract | The pathogenesis of hepatic encephalopathy is multifactorial, involving gut-derived toxins such as ammonia, which has been demonstrated to induce oxidative stress. Therefore, a primary hepatic encephalopathy treatment target is reducing ammonia production in the gastrointestinal tract. AST-120, an oral adsorbent of engineered activated carbon microspheres with surface areas exceeding 1600 m(2) /g, acts as a sink for neurotoxins and hepatotoxins present in the gut. We evaluated the capacity of AST-120 to adsorb ammonia in vitro and to lower blood ammonia, oxidative stress and brain edema in cirrhotic rats. Cirrhosis was induced in rats by bile duct ligation for 6 weeks. AST-120 was administered by gavage preventively for 6 weeks (0.1, 1, and 4 g/kg/day). In addition, AST-120 was evaluated as a short-term treatment for 2 weeks and 3 days (1 g/kg/day) and as a sink to adsorb intravenously infused ammonium acetate. In vitro, AST-120 efficiently adsorbed ammonia. Ammonia levels significantly decreased in a dose-dependent manner for all AST-120-treated bile duct-ligated rats (nontreated: 177.3 ± 30.8 μM; AST-120, 0.1 g/kg/day: 121.9 ± 13.8 μM; AST-120, 1 g/kg/day: 80.9 ± 30.0 μM; AST-120, 4 g/kg/day: 48.8 ± 19.6 μM) and significantly correlated with doses of AST-120 (r = -0.6603). Brain water content and locomotor activity normalized after AST-120 treatments, whereas arterial reactive oxygen species levels remained unchanged. Furthermore, AST-120 significantly attenuated a rise in arterial ammonia after ammonium acetate administration (intravenously). Conclusion:AST-120 treatment decreased arterial ammonia levels, normalized brain water content and locomotor activity but did not demonstrate an effect on systemic oxidative stress. Also, AST-120 acts as an ammonia sink, efficiently removing blood-derived ammonia. Additional studies are warranted to evaluate the effects of AST-120 on hepatic encephalopathy in patients with advanced liver disease. (HEPATOLOGY 2011;). | fr |
dcterms.language | eng | fr |
UdeM.VersionRioxx | Version acceptée / Accepted Manuscript | |
oaire.citationTitle | Hepatology | |
oaire.citationVolume | 53 | |
oaire.citationIssue | 6 | |
oaire.citationStartPage | 1995 | |
oaire.citationEndPage | 2002 |
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