title: Preventive effects of astaxanthin on diethylnitrosamine-induced liver tumorigenesis in C57/BL/KsJ-db/db obese mice.
abstract: OBJECTIVE
  Obesity and its related metabolic abnormalities, including oxidative stress and adipokine imbalance, are involved in liver carcinogenesis. The aim of the present study was to examine the effects of astaxanthin, a powerful biological antioxidant, on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-db/db (db/db) obese mice.
  
  
  METHODS
  Male db/db mice were given a single i.p. injection of DEN (25 mg/kg bodyweight) at 2 weeks of age, and, subsequently, from 4 weeks of age, they were fed a diet containing 200 p.p.m. astaxanthin throughout the experiment.
  
  
  RESULTS
  Twenty weeks of astaxanthin administration significantly inhibited the development of hepatocellular neoplasms (liver cell adenoma and hepatocellular carcinoma) and the hepatic expression of cyclin D1 mRNA compared with the basal diet group in DEN-treated db/db mice. Astaxanthin administration in DEN-treated experimental mice markedly reduced the derivatives of reactive oxygen metabolites/biological antioxidant potential ratio, which is a serum marker of oxidative stress, while increasing the mRNA expression of the antioxidant enzymes superoxide dismutase 2 and glutathione peroxidase 1 in the liver and white adipose tissue. The serum levels of adiponectin increased after astaxanthin administration in these mice.
  
  
  CONCLUSIONS
  Dietary astaxanthin prevented the development of liver tumorigenesis in obese mice by improving oxidative stress and ameliorating serum adiponectin level. Therefore, astaxanthin may be useful in the chemoprevention of liver tumorigenesis in obese individuals.
authors.affiliation: Departments of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Departments of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Departments of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shirakami
authors.affiliation: Departments of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tsuneyuki
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Departments of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Ideta
authors.affiliation: Departments of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kochi
authors.affiliation: Departments of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Departments of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Departments of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
keywords: adiponectin; astaxanthin; liver tumorigenesis; obesity; oxidative stress