Hepatocyte transplants improve liver function and encephalopathy in portacaval shunted rats.
OBJECTIVE
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.
Department of Hormone Biochemistry, Medical University of Lodz, Lodz, Poland.
Wieslawa Agnieszka
WA
Fogel
Anna
A
Stasiak
Michał
M
Maksymowicz
Jozef
J
Kobos
Mercedes
M
Unzeta
Miroslaw
M
Mussur
D000428:Alcohol Drinking / Q000473:pathology / Q000628:therapy; D000818:Animals; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D022781:Hepatocytes / Q000502:physiology* / Q000637:transplantation*; D008099:Liver / Q000502:physiology*; D008297:Male; D011167:Portacaval Shunt, Surgical / Q000009:adverse effects; D051381:Rats; D011917:Rats, Inbred Lew
Amine neurotransmitters; Hepatic encephalopathy; Hepatocyte transplantation; Portacaval shunt in rat; Voluntary alcohol intake