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1.
Clin Nutr ; 33(2): 302-10, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23755843

ABSTRACT

BACKGROUND AND AIMS: 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. METHOD: 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. CONCLUSION: This study showed the efficacy of coffee in the prevention of hepatitis and liver carcinogenesis in the LEC model.


Subject(s)
Coffee/chemistry , Hepatitis/prevention & control , Inflammation/metabolism , Liver Neoplasms/prevention & control , Adenosine Triphosphatases/genetics , Adenosine Triphosphatases/metabolism , Alanine Transaminase/metabolism , Animals , Caffeine/pharmacology , Cation Transport Proteins/genetics , Cation Transport Proteins/metabolism , Cinnamates/pharmacology , Copper/adverse effects , Copper/pharmacokinetics , Copper-Transporting ATPases , Gene Expression/drug effects , Glutathione Transferase/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Iron/adverse effects , Iron/pharmacokinetics , Liver/drug effects , Liver/metabolism , Liver Neoplasms/chemically induced , Male , Oxidative Stress/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Inbred LEC , Smad2 Protein/genetics , Smad2 Protein/metabolism , Smad3 Protein/genetics , Smad3 Protein/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
2.
Anim Sci J ; 83(5): 367-74, 2012 May.
Article in English | MEDLINE | ID: mdl-22574788

ABSTRACT

Genetic improvement of resistance to infectious diseases is a challenging goal in animal breeding. Infection resistance involves multiple immunological characteristics, including natural and acquired immunity. In the present study, we developed an experimental model based on genetic selection, to improve immunological phenotypes. We selectively established three mouse lines based on phagocytic activity, antibody production and the combination of these two phenotypes. We analyzed the immunological characteristics of these lines using a lipopolysaccharide (LPS), which is one of the main components of Gram-negative bacteria. An intense immunological reaction was induced in each of the three mouse lines. Severe loss of body weight and liver damage were observed, and a high level of cytokine messenger RNA was detected in the liver tissue. The mouse line established using a combination of the two selection standards showed unique characteristics relative to the mouse lines selected on the basis of a single phenotype. Our results indicate that genetic selection and breeding is effective, even for immunological phenotypes with a relatively low heritability. Thus, it may be possible to improve resistance to infectious diseases by means of genetic selection.


Subject(s)
Adaptive Immunity , Immunity, Innate , Lipopolysaccharides/immunology , Selection, Genetic , Animals , Antibody Formation/physiology , Bacterial Infections , Cytokines/analysis , Disease Susceptibility , Genetic Predisposition to Disease/genetics , Mice , Phagocytosis , Phenotype , Real-Time Polymerase Chain Reaction , Transaminases/metabolism
3.
Nat Genet ; 30(3): 253-4, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11836501

ABSTRACT

Here we report that the lifespan of mice cloned from somatic cells is significantly shorter than that of genotype- and sex-matched controls, most likely due to severe pneumonia and hepatic failure. This finding demonstrates the possibility of long-term deleterious effects of somatic-cell cloning, even after normal birth.


Subject(s)
Cloning, Organism , Hybrid Cells , Survival Analysis , Animals , L-Lactate Dehydrogenase/metabolism , Liver Failure , Mice , Pneumonia , Quaternary Ammonium Compounds/metabolism
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