title: Coffee consumption delays the hepatitis and suppresses the inflammation related gene expression in the Long-Evans Cinnamon rat.
abstract: OBJECTIVE
  Large-scale epidemiological studies have shown that drinking more than two cups of coffee per day reduces the risks of hepatitis and liver cancer. However, the heterogeneity of the human genome requires studies of experimental animal models with defined genetic backgrounds to evaluate the coffee effects on liver diseases. We evaluated the efficacy of coffee consumption with one of experimental animal models for human disease.
  
  
  METHODS
  We used the Long Evans Cinnamon (LEC) rat, which onsets severe hepatitis and high incidence of liver cancer, due to the accumulation of copper and iron in livers caused by the genetic mutation in Atp7B gene, and leading to the continuous oxidative stress. We determined the expression of inflammation related genes, and amounts of copper and iron in livers, and incidence of the pre-neoplastic foci in the liver tissue of LEC rats.
  
  
  RESULTS
  Coffee administration for 25 weeks delayed the occurrence of hepatitis by two weeks, significantly improved survival, reduced the expression of inflammatory cytokines, and reduced the incidence of small pre-neoplastic liver foci in LEC rats. There was no significant difference in the accumulation of copper and iron in livers, indicating that coffee administration does not affect to the metabolism of these metals. These findings indicate that drinking coffee potentially prevents hepatitis and liver carcinogenesis through its anti-inflammatory effects.
  
  
  CONCLUSIONS
  This study showed the efficacy of coffee in the prevention of hepatitis and liver carcinogenesis in the LEC model.
authors.affiliation: Tohoku University, Graduate School of Agricultural Science, 1-1 Tsutsumidori, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Katayama
authors.affiliation: Tohoku University, Graduate School of Agricultural Science, 1-1 Tsutsumidori, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Donai
authors.affiliation: Faculty of Agriculture, University of Miyazaki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakakibara
authors.affiliation: Tohoku University, Graduate School of Agricultural Science, 1-1 Tsutsumidori, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ohtomo
authors.affiliation: Central Experimental Animal Center, Teikyo University School of Medicine, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyagawa
authors.affiliation: Tohoku University, Graduate School of Agricultural Science, 1-1 Tsutsumidori, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kuroda
authors.affiliation: Department of Health Dietetics, Faculty of Health and Medical Sciences, Teikyo Heisei University, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kodama
authors.affiliation: Institute for Animal Reproduction, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Institute of Animal Experimentation, Tohoku University, Graduate School of Medicine, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kasai
authors.affiliation: Tohoku University, Graduate School of Agricultural Science, 1-1 Tsutsumidori, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nishimori
authors.affiliation: Tohoku University, Graduate School of Agricultural Science, 1-1 Tsutsumidori, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Tohoku University, Graduate School of Agricultural Science, 1-1 Tsutsumidori, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Tohoku University, Graduate School of Agricultural Science, 1-1 Tsutsumidori, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Aso
authors.affiliation: Tohoku University, Graduate School of Agricultural Science, 1-1 Tsutsumidori, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Isogai
authors.affiliation: National Institute for Environmental Studies, Center for Environmental Risk Research, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Sone
authors.affiliation: Tohoku University, Graduate School of Agricultural Science, 1-1 Tsutsumidori, Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan. Electronic address: tomofukuda@bios.tohoku.ac.jp.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology; D003069:Coffee / Q000737:chemistry*; D003300:Copper / Q000009:adverse effects / Q000493:pharmacokinetics; D000073840:Copper-Transporting ATPases; D015870:Gene Expression / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D006505:Hepatitis / Q000517:prevention & control*; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000009:adverse effects / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020332:Rats, Inbred LEC; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D002934:Cinnamates; D003069:Coffee; D015850:Interleukin-6; D012333:RNA, Messenger; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D014409:Tumor Necrosis Factor-alpha; C029010:cinnamic acid; D002110:Caffeine; D003300:Copper; D007501:Iron; D005982:Glutathione Transferase; D000410:Alanine Transaminase; D000251:Adenosine Triphosphatases; C550619:Atp7b protein, rat; D000073840:Copper-Transporting ATPases
keywords: Coffee; Cytokine; Experimental animal model; Hepatitis; Liver cancer; Pre-neoplastic foci