Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.
Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.
Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan. motoh@clin.medic.mie-u.ac.jp
Motoh
M
Iwasa
Yoshinao
Y
Kobayashi
Rumi
R
Mifuji-Moroka
Nagisa
N
Hara
Hirohide
H
Miyachi
Ryosuke
R
Sugimoto
Hideaki
H
Tanaka
Naoki
N
Fujita
Esteban C
EC
Gabazza
Yoshiyuki
Y
Takei
D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride; D019587:Dietary Supplements; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D016019:Survival Analysis; D000071161:Forkhead Box Protein O1
D000597:Amino Acids, Branched-Chain; D002251:Carbon Tetrachloride; D051858:Forkhead Transcription Factors; D005947:Glucose; D007501:Iron; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1