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Basic science (liver)
PMO-128 Effects of oral nanoporous carbon therapy in leptin null mice as a model of non-alcoholic steatohepatitis
  1. J Macnaughtan1,
  2. J Soeda1,
  3. A Mouralidarane1,
  4. S Sandeman2,
  5. C Howell2,
  6. S Milkhalovsky2,
  7. O Kozynchenko3,
  8. S Tennison3,
  9. N Davies1,
  10. R Mookerjee1,
  11. J Oben1,
  12. R Jalan1
  1. 1Hepatology, UCL, London, UK
  2. 2Centre for Biomedical and Health Science, University of Brighton, Brighton, UK
  3. 3MastCarbon, Guildford, UK

Abstract

Introduction Endotoxaemia is implicated in the pathogenesis of non-alcoholic fatty liver disease. Modulation of intra-luminal factors driving bacterial translocation may have the capacity to impact on the natural history of the disease. 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. We sought to determine their biological effects in leptin null mice, which are hyperphagic and obese with evident steatohepatitis and to ascertain whether nanoporous carbons can reverse established non-alcoholic steatohepatitis (NASH) in these animals.

Methods 10 lep/lep null and 10 heterozygote male mice were randomised to receive powdered chow ± carbon (0.4 g/100 g body weight/day) for 4 weeks. Extent of liver injury was assessed by serum levels of ALT. Additionally, non-parenchymal cells were isolated and the Kupffer cell (KC) population characterised by flow cytometry as those cells expressing F4/80, CD68 and CD11b. Reactive oxygen species (ROS) production by isolated KCs was also assayed. Hepatic TLR-4 expression as a surrogate of endotoxaemia was determined by immunohistochemistry.

Results In lep/lep mice, oral carbon treatment was associated with a significant reduction in ALT 889±280 IU/ml to 408±42 IU/ml (p<0.05). Total KC population was found to be increased in lep/lep mice compared to heterozygote control with a significant reduction observed with carbon treatment (p<0.05). A significant reduction in KCs ROS production was also observed in carbon treated lep/lep mice (p<0.05) compared to untreated lep/lep controls. A significant reduction in the F4/80+, CD68, CD11b+ cell sub-population in lep/lep in the presence of carbon treatment group was also observed (p<0.05). Moreover, hepatic TLR-4 expression was reduced in carbon-treated lep/lep mice compared to non-treated controls. Finally, we observed a trend towards reduction in final body weight in carbon-treated lep/lep mice compared to untreated controls group (p=0.095).

Conclusion Oral nanoporous carbon through modulating endotoxaemia and KC function may be a promising therapy in NASH.

Competing interests None declared.

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