title: Protective effects of hypothalamic beta-endorphin neurons against alcohol-induced liver injuries and liver cancers in rat animal models.
abstract: BACKGROUND
  Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer.
  
  
  METHODS
  Male rats received either BEP neuron transplants or control transplants in the hypothalamus and were randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer.
  
  
  RESULTS
  Alcohol feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased the levels of triglyceride, hepatic stellate cell (HSC) activation factors, and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocellular carcinoma (HCC), collagen deposition, numbers of preneoplastic foci, levels of HSC activation factors and catecholamines, as well as inflammatory milieu and increased the levels of natural killer cell cytotoxic factors in the liver.
  
  
  CONCLUSIONS
  These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and HCC formation possibly via influencing the immune function.
authors.affiliation: Endocrine Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey.
authors.forename: Sengottuvelan
authors.initials: S
authors.lastname: Murugan
authors.forename: Nadka
authors.initials: N
authors.lastname: Boyadjieva
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Sarkar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007031:Hypothalamus / Q000637:transplantation*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009474:Neurons / Q000637:transplantation*; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D001615:beta-Endorphin
chemical_list: D000431:Ethanol; D001615:beta-Endorphin
keywords: Alcoholic Liver Disease; Hepatocellular Carcinoma; Natural Killer Cells; Neuroimmune System; Stress Hormones