title: Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats.
abstract: BACKGROUND
  Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines.
  
  
  OBJECTIVE
  The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL).
  
  
  METHODS
  Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-alpha, IL-1beta and IL-6 were also assayed in plasma samples.
  
  
  RESULTS
  In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p<0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p<0.05-p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment.
  
  
  CONCLUSIONS
  Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.
authors: Marmara University, School of Medicine, Department of Physiology, Haydarpaşa, Istanbul 34668, Turkey.
authors: Sevgin Ozlem
authors: SO
authors: Işeri
authors: Göksel
authors: G
authors: Sener
authors: Beyhan
authors: B
authors: Saglam
authors: Feriha
authors: F
authors: Ercan
authors: Nursal
authors: N
authors: Gedik
authors: Berrak C
authors: BC
authors: Yeğen
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000187:drug effects* / Q000601:surgery; D003094:Collagen / Q000378:metabolism; D054439:Ghrelin / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D054439:Ghrelin; D003094:Collagen; D009195:Peroxidase