Open AccessHepatocyte Transplants Improve Liver Function and Encephalopathy in Portacaval Shunted Rats
Author(s) -
Fogel Wieslawa Agnieszka,
Stasiak Anna,
Maksymowicz Michał,
Kobos Jozef,
Unzeta Mercedes,
Mussur Miroslaw
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12265
Subject(s) - hepatic encephalopathy , hepatocyte , encephalopathy , liver transplantation , liver function , medicine , function (biology) , portacaval shunt , gastroenterology , chemistry , biology , transplantation , microbiology and biotechnology , biochemistry , portal hypertension , cirrhosis , in vitro
Summary Aim Rats with portacaval shunt ( PCS ) are useful experimental models of human hepatic encephalopathy in chronic liver dysfunction. We have previously shown that PCS modifies amine neurotransmitter systems in the CNS and increases voluntary alcohol intake by rats. Hepatocyte transplantation, used in acute liver failure, has recently also been applied to chronic liver diseases, which prompted us to investigate whether the altered brain amine system and the drinking behavior in long‐term shunted rats could be normalized by hepatocyte transplants. Methods Hepatocytes, isolated from syngeneic donors by collagenase digestion, were injected (3 × 10 6 cells/rat) into the pancreatic tail region, 6 months after PCS . Hepatic function was evaluated by measuring urine urea and plasma L‐histidine concentrations. A free choice test with two bottles (tap water and 10% ethyl alcohol) was performed for 3 days to assess the rats’ preference for alcohol. The rats were euthanized 2 months posttransplantation. Brain histamine and 5‐hydroxyindoleacetic acid (5‐ HIAA ) levels were measured by radioenzymatic assay and by HPLC ‐ EC , respectively, N‐ tele ‐methylhistamine by GC / MS while MAOA and MAOB activities by isotopic procedures. Results Portacaval shunt rats with hepatocyte transplants gave more urea than before transplantation, with lower plasma L‐His levels and higher body weight versus the PCS counterparts. Also, those rats consumed less alcohol. The CNS amines and 5‐ HIAA concentrations, as well as MAO ‐B activity, being abnormally high in untreated PCS rats, significantly reduced after PCS hepatocyte treatment. Conclusions The results support the therapeutic values of hepatocyte transplants in chronic liver diseases and the temporary character of PCS ‐exerted CNS dysfunctions.