Introduction Gut-derived bacterial products and associated dysregulated inflammatory response play a central role in the pathogenesis of cirrhosis. Therapeutic options to target these factors are currently limited to long-term antibiotics. Nanoporous carbons are non-absorbable, synthetic materials which are safe with porosity manipulated for adsorption of middle and high molecular weight molecules and surface chemistry modified to alter adsorption capacity for biological molecules such as cytokines and endotoxin. We sought to determine their biological effects in bile-duct ligated rats as a model of cirrhosis.
Methods 131 male Sprague-Dawley rats underwent bile duct-ligation or sham biliary surgery. Animals were pair fed with or without oral carbon therapy 2 weeks from surgery until completion of the experiment at 4–5 weeks. Intra-peritoneal lipopolysaccharide (LPS) was administered to four subgroups 3.5 h prior to completion of the study. The following groups were studied: Sham (n=16), Sham + carbon (n=15), Sham + LPS (n=11), Sham+LPS+carbon (n=10), BDL (n=27), BDL + carbon (n=26), BDL+LPS (n=10), BDL+LPS+carbon (n=16). Portal haemodynamics were performed on 93 rats and Kupffer cell (KC) numbers and Reactive oxygen species (ROS) production assessed by flow cytometry in a sub-group of animals. Liver biochemistry and portal venous cytokines were performed.
Results A significant reduction in portal pressure was observed in BDL+LPS (mean 18.05±0.88 mm Hg untreated, 10.17±1.07 mm Hg with carbon, p<0.05) and BDL (mean 12.57±0.43 mm Hg untreated, 11.02±0.28 mm Hg with carbon, p<0.05) groups following carbon treatment. A significant reduction in ALT was observed in the carbon treated BDL+LPS (p<0.05) and BDL groups (p<0.05). Carbon treatment in BDL rats was associated with a significant reduction in LPS-induced ROS production. A trend towards reduction in portal venous IL-4 and IL-10 was observed in carbon-treated BDL rats. No significant difference in portal venous TNF-α was observed. Finally, a significant increase in body mass was observed in the BDL carbon-treated group (p<0.05).
Conclusion Oral nanoporous carbon therapy results in a significant reduction in portal pressure and liver biochemistry associated with a reduction in endotoxin-induced KC ROS production. We postulate therefore, that the effect of nanoporous carbon is possibly via a reduction in endotoxin induced KC stimulation.
Competing interests None declared.
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