title: Inhibition of diethylnitrosamine-initiated alcohol-promoted hepatic inflammation and precancerous lesions by flavonoid luteolin is associated with increased sirtuin 1 activity in mice.
abstract: BACKGROUND
  Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against cancer. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen initiated alcohol-promoted pre-neoplastic liver lesion mouse model.
  
  
  METHODS
  C57BL/6 mice were injected with diethylnitrosamine (DEN) [i.p. 25 mg/kg of body weight (BW)] at 14 days of age. At 8 weeks of age mice were group pair-fed with Lieber-DeCarli liquid control diet or alcoholic diet [ethanol (EtOH) diet, 27% total energy from ethanol] and supplemented with a dose of 30 mg luteolin/kg BW per day for 21 days.
  
  
  RESULTS
  DEN-injected mice fed EtOH diet displayed a significant induction of pre-neoplastic lesions, a marker associated with presence of steatosis and inflammation. Dietary luteolin significantly reduced the severity and incidence of hepatic inflammatory foci and steatosis in DEN-injected mice fed EtOH diet, as well the presence of preneoplastic lesions. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1) among all groups; however, luteolin supplementation significantly reversed alcohol-reduced SIRT1 activity assessed by the ratio of acetylated and total forkhead box protein O1 (FoXO1) and SIRT1 target proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α).
  
  
  CONCLUSIONS
  Dietary intake of luteolin prevents alcohol promoted pre-neoplastic lesions, potentially mediated by SIRT1 signaling pathway.
authors.affiliation: 1 Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 2 Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil ; 3 Obesity and Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 4 Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
authors.forename: Bruna Paola Murino
authors.initials: BP
authors.lastname: Rafacho
authors.affiliation: 1 Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 2 Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil ; 3 Obesity and Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 4 Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
authors.forename: Camilla Peach
authors.initials: CP
authors.lastname: Stice
authors.affiliation: 1 Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 2 Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil ; 3 Obesity and Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 4 Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.affiliation: 1 Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 2 Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil ; 3 Obesity and Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 4 Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greenberg
authors.affiliation: 1 Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 2 Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil ; 3 Obesity and Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 4 Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Ausman
authors.affiliation: 1 Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 2 Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil ; 3 Obesity and Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, MA, USA ; 4 Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Wang
keywords: Luteolin; diethylnitrosamine (DEN); inflammation; liver cancer; sirtuin 1 (SIRT1)