PMID- 25156780
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20211021
IS  - 1478-3231 (Electronic)
IS  - 1478-3223 (Print)
IS  - 1478-3223 (Linking)
VI  - 35
IP  - 4
DP  - 2015 Apr
TI  - Branched-chain amino acids reduce hepatic iron accumulation and oxidative stress 
      in hepatitis C virus polyprotein-expressing mice.
PG  - 1303-14
LID - 10.1111/liv.12675 [doi]
AB  - BACKGROUND & AIMS: Branched-chain amino acids (BCAA) reduce the incidence of 
      hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the 
      mechanisms that underlie these effects remain unknown. Previously, we reported 
      that oxidative stress in male transgenic mice that expressed hepatitis C virus 
      polyprotein (HCVTgM) caused hepatic iron accumulation by reducing hepcidin 
      transcription, thereby leading to HCC development. This study investigated 
      whether long-term treatment with BCAA reduced hepatic iron accumulation and 
      oxidative stress in iron-overloaded HCVTgM and in patients with HCV-related 
      advanced fibrosis. METHODS: Male HCVTgM were fed an excess-iron diet that 
      comprised either casein or 3.0% BCAA, or a control diet, for 6 months. RESULTS: 
      For HCVTgM, BCAA supplementation increased the serum hepcidin-25 levels and 
      antioxidant status [ratio of biological antioxidant potential (BAP) relative to 
      derivatives of reactive oxygen metabolites (dROM)], decreased the hepatic iron 
      contents, attenuated reactive oxygen species generation, and restored 
      mitochondrial superoxide dismutase expression and mitochondrial complex I 
      activity in the liver compared with mice fed the control diet. After 48 weeks of 
      BCAA supplementation in patients with HCV-related advanced fibrosis, BAP/dROM and 
      serum hepcidin-25 increased and serum ferritin decreased compared with the 
      pretreatment levels. CONCLUSIONS: BCAA supplementation reduced oxidative stress 
      by restoring mitochondrial function and improved iron metabolism by increasing 
      hepcidin-25 in both iron-overloaded HCVTgM and patients with HCV-related advanced 
      fibrosis. These activities of BCAA may partially account for their inhibitory 
      effects on HCC development in cirrhosis patients.
CI  - (c) 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.
FAU - Korenaga, Masaaki
AU  - Korenaga M
AD  - Department of Hepatology and Pancreatology, Kawasaki Medical School, Okayama, 
      Japan; The Research Center for Hepatitis and Immunology, National Center for 
      Global Health and Medicine (NCGM), Chiba, Japan.
FAU - Nishina, Sohji
AU  - Nishina S
FAU - Korenaga, Keiko
AU  - Korenaga K
FAU - Tomiyama, Yasuyuki
AU  - Tomiyama Y
FAU - Yoshioka, Naoko
AU  - Yoshioka N
FAU - Hara, Yuichi
AU  - Hara Y
FAU - Sasaki, Yusuke
AU  - Sasaki Y
FAU - Shimonaka, Yasushi
AU  - Shimonaka Y
FAU - Hino, Keisuke
AU  - Hino K
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140918
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (Amino Acids, Branched-Chain)
RN  - 0 (Antioxidants)
RN  - 0 (Biomarkers)
RN  - 0 (Dietary Proteins)
RN  - 0 (Hepcidins)
RN  - 0 (Polyproteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Viral Proteins)
RN  - 0 (hepcidin 25, human)
RN  - 9007-73-2 (Ferritins)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Amino Acids, Branched-Chain/*administration & dosage
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Biomarkers/blood
MH  - Dietary Proteins/*administration & dosage
MH  - Disease Models, Animal
MH  - Female
MH  - Ferritins/blood
MH  - Hepacivirus/genetics/*metabolism
MH  - Hepatitis C/blood/*diet therapy/genetics/metabolism
MH  - Hepcidins/blood
MH  - Humans
MH  - Iron/*metabolism
MH  - Japan
MH  - Liver/*metabolism
MH  - Liver Cirrhosis/blood/*diet therapy/genetics/metabolism
MH  - Male
MH  - Mice, Transgenic
MH  - *Oxidative Stress
MH  - Polyproteins/genetics/*metabolism
MH  - Reactive Oxygen Species/blood
MH  - Time Factors
MH  - Treatment Outcome
MH  - Viral Proteins/genetics/*metabolism
PMC - PMC4409847
OTO - NOTNLM
OT  - hepatic mitochondrial dysfunction
OT  - hepatitis C virus
OT  - hepcidin-25
OT  - iron metabolic disorder
OT  - reactive oxygen species
EDAT- 2014/08/27 06:00
MHDA- 2015/12/17 06:00
PMCR- 2015/04/25
CRDT- 2014/08/27 06:00
PHST- 2014/03/04 00:00 [received]
PHST- 2014/08/16 00:00 [accepted]
PHST- 2014/08/27 06:00 [entrez]
PHST- 2014/08/27 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
PHST- 2015/04/25 00:00 [pmc-release]
AID - 10.1111/liv.12675 [doi]
PST - ppublish
SO  - Liver Int. 2015 Apr;35(4):1303-14. doi: 10.1111/liv.12675. Epub 2014 Sep 18.