AST-120 (spherical carbon adsorbent) lowers ammonia levels and attenuates brain edema in bile duct-ligated rats

Hepatology. 2011 Jun;53(6):1995-2002. doi: 10.1002/hep.24273.


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 m2/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / administration & dosage
  • Acetates / adverse effects
  • Ammonia / blood*
  • Animals
  • Bile Ducts / surgery*
  • Brain Edema / etiology*
  • Brain Edema / physiopathology
  • Brain Edema / prevention & control*
  • Carbon / administration & dosage
  • Carbon / pharmacology
  • Carbon / therapeutic use*
  • Dose-Response Relationship, Drug
  • Infusions, Intravenous
  • Ligation / adverse effects
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / etiology*
  • Male
  • Microspheres
  • Models, Animal
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Oxides / administration & dosage
  • Oxides / pharmacology
  • Oxides / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley


  • Acetates
  • Oxides
  • Carbon
  • Ammonia
  • AST 120
  • ammonium acetate