title: Long-term binge and escalating ethanol exposure causes necroinflammation and fibrosis in rat liver.
abstract: BACKGROUND
  To investigate whether "binge" and escalating alcohol exposure in the rat influences the development of pathological liver injury.
  
  
  METHODS
  Time courses for the formation of eicosanoids by cyclooxygenase (COX), oxidative stress and nitrosative stress production, expression of hypoxia-inducible factor 1 (HIF-1), cytokines, hepatic tissue necroinflammation, and fibrosis were assessed in rats during 16 weeks of daily alcohol gavage.
  
  
  RESULTS
  In this model of binge and escalating levels of alcohol, hepatic steatosis, necrosis, and inflammation as well as fibrosis were increased over the 16-week period. The levels of COX-2, oxidative stress, nitrosative stress, HIF-1, proinflammatory mediators (tumor necrosis factor-α, interleukin 1(β)  [IL-1(β) ], IL-6), and procollagen-I were increased over the 16-week period. The content of IL-10 in rat serum increased at the end of 4 and 8 weeks but decreased thereafter and was significantly decreased at 12 and 16 weeks.
  
  
  CONCLUSIONS
  A rat model of alcoholic liver disease (ALD) with long-term binge and escalating ethanol exposure was developed. Our data support the hypothesis that enhanced eicosanoid production by COX, oxidative stress and nitrosative stress, HIF-1, and the imbalance between pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of ALD.
authors.affiliation: Department of Infectious Disease , Third Hospital, Hebei Medical University, Shijiazhuang, China. doctorzhoujy@163.com
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Zhou
authors.forename: Zhi-An
authors.initials: ZA
authors.lastname: Jiang
authors.forename: Cai-Yan
authors.initials: CY
authors.lastname: Zhao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhen
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Amin A
authors.initials: AA
authors.lastname: Nanji
mesh_terms: D000818:Animals; D063425:Binge Drinking / Q000097:blood / Q000473:pathology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011347:Procollagen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D016207:Cytokines; D051793:Hypoxia-Inducible Factor 1; D018836:Inflammation Mediators; D011347:Procollagen; C002744:3-nitrotyrosine; D000431:Ethanol; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2