AST-120 (spherical carbon adsorbent) lowers ammonia levels and attenuates brain edema in bile duct–ligated rats
✍ Scribed by Cristina R. Bosoi; Christian Parent-Robitaille; Keith Anderson; Mélanie Tremblay; Christopher F. Rose
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 766 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
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 6 30.8 lM; AST-120, 0.1 g/kg/day: 121.9 6 13.8 lM; AST-120, 1 g/kg/day: 80.9 6 30.0 lM; AST-120, 4 g/kg/day: 48.8 6 19.6 lM) and significantly correlated with doses of AST-120 (r 5 20.6603). 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. (