582 METAL METABOLISM IMPAIRMENT IN PATIENTS WITH HEPATIC ENCEPHALOPATHY

Abstract

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. The aims of this study were to determine whether oral administration of these carbons would prevent the complications of cirrhosis. Methods: 131 male Sprague-Dawley rats underwent bile ductligation or sham biliary surgery. Animals were pair fed with or without oral carbon therapy two weeks from surgery until completion of the experiment at 4–5 weeks. Intraperitoneal lipopolysaccharide (LPS) was administered to 4 subgroups 3.5 hours prior to completion of 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 population and ROS production were performed by flow cytometry in a subgroup of animals. Biochemistry and portal venous cytokines were measured. Results: A significant reduction in portal pressure was observed in BDL+LPS (mean 18.1mmHg (0.88) untreated, 10.2mmHg (1.07) with carbon, p = 0.0007) and BDL (mean 12.6mmHg (0.43) untreated, 11.0mmHg (0.28) with carbon, p = 0.004) groups following carbon treatment. A significant reduction in ALT was observed in the carbon treated BDL+LPS (p =0.01) and BDL groups (p = 0.04). Carbon treatment in BDL rats was associated with a significant reduction in LPS-induced ROS production by the Kupffer cells. A trend towards reduction in portal venous IL-4 and IL-10 were observed in carbontreated BDL rats. A significant increase in final body mass was observed in the BDL carbon-treated group (p =0.03). Conclusions: The data from this study suggests that nanoporous carbon is a novel approach to reducing gut translocation which prevents Kupffer cell activation thereby preventing portal hypertension.