title: Oral branched-chain amino acid granules improve structure and function of human serum albumin in cirrhotic patients.
abstract: OBJECTIVE
  The aim of this study was to evaluate structural and functional alterations of human serum albumin (HSA), with a special focus on the oxidized and reduced forms, in patients with chronic liver disease. We also investigated whether oral branched-chain amino acid (BCAA) supplementation could induce structural changes and improve the functions of HSA.
  
  
  METHODS
  The proportion of reduced and oxidized HSA was determined in 16 healthy controls and in 20 chronic hepatitis and 100 cirrhotic patients with stable conditions. To evaluate the functional properties of HSA, this study focused on the antioxidant and binding functions. The radical scavenging activity and binding ability of purified HSA were measured in 68 participants. After BCAA administration for 6 months, 29 patients were evaluated for HSA structural changes, with 19 out of the 29 patients also analyzed for HSA functional changes.
  
  
  RESULTS
  There was a significant decrease in the amounts of reduced HSA in conjunction with liver disease progression. Receiver operating characteristic curve analysis demonstrated that the levels of reduced HSA had high accuracy in determining disease progression. Functional alterations were strongly correlated to the levels of reduced HSA. BCAA supplementation led to substantial increases in the amount of reduced HSA. The altered HSA was able to scavenge significantly more radicals and restore the binding ability.
  
  
  CONCLUSIONS
  This study describes structural alterations and functional disturbances of HSA in patients with chronic liver disease, and indicates that the levels of reduced HSA might reflect disease progression and the functional properties of HSA. Moreover, oral BCAA supplementation increases the amount of reduced HSA, thereby leading to the restoration of HSA function in cirrhotic patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuou-ku, Kumamoto City, Kumamoto, 860-8556, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Setoyama
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuou-ku, Kumamoto City, Kumamoto, 860-8556, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Kumamoto, 862-0973, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Nagumo
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuou-ku, Kumamoto City, Kumamoto, 860-8556, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Naoe
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuou-ku, Kumamoto City, Kumamoto, 860-8556, Japan.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuou-ku, Kumamoto City, Kumamoto, 860-8556, Japan.
authors.forename: Youko
authors.initials: Y
authors.lastname: Yoshimaru
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuou-ku, Kumamoto City, Kumamoto, 860-8556, Japan.
authors.forename: Masakuni
authors.initials: M
authors.lastname: Tateyama
authors.affiliation: Kumamoto Rosai Hospital, Yatsushiro City, Kumamoto, 866-0826, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Kumamoto, 862-0973, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Faculty of Pharmaceutical Sciences and DDS Research Institute, Sojo University, Kumamoto City, Kumamoto, 860-0082, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Kumamoto, 862-0973, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuou-ku, Kumamoto City, Kumamoto, 860-8556, Japan. sasakiy@kumamoto-u.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage* / Q000378:metabolism; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism; D016022:Case-Control Studies; D019587:Dietary Supplements; D018450:Disease Progression; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000378:metabolism; D006521:Hepatitis, Chronic / Q000097:blood / Q000628:therapy; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D000075462:Serum Albumin, Human / Q000378:metabolism*
chemical_list: D000597:Amino Acids, Branched-Chain; D000975:Antioxidants; D016166:Free Radical Scavengers; D000075462:Serum Albumin, Human
keywords: Antioxidant; Biomarker; Oxidative stress; Structure–function relationship