ABSTRACT
BACKGROUND AND AIMS: 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. CONCLUSION: 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.
Subject(s)
Amino Acids, Branched-Chain/administration & dosage , Antioxidants/administration & dosage , Liver Cirrhosis/therapy , Serum Albumin, Human/metabolism , Administration, Oral , Aged , Amino Acids, Branched-Chain/metabolism , Antioxidants/metabolism , Case-Control Studies , Dietary Supplements , Disease Progression , Female , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/metabolism , Hepatitis, Chronic/blood , Hepatitis, Chronic/therapy , Humans , Liver Cirrhosis/blood , Male , Middle Aged , Oxidation-ReductionABSTRACT
In recent world-wide studies, chitosans were tested as a dietary supplement for inhibiting the absorption of certain lipids and bile acids. We previously demonstrated the antioxidative and renoprotective potential of chitosan supplementation in chronic renal failure using 5/6 nephrectomized rats. In this study, we report the effects of chitosan on oxidative stress and related factors in hemodialysis patients. The ingestion of chitosan over a 12-week period resulted in a significant decrease in serum indoxyl sulfate and phosphate levels, compared with the levels prior to the start of the study. The ingestion of chitosan also resulted in a lowered ratio of oxidized to reduced albumin and a decrease in the level of advanced oxidized protein products. In in vitro studies, chitosan solutions were found to bind 38.5% of the indoxyl sulfate and 17.8% of the phosphate, respectively. Further, the oxidized albumin ratio was correlated with serum indoxyl sulfate levels in vivo. These results suggest that the ingestion of chitosan results in a significant reduction in the levels of pro-oxidants, which include uremic toxins, in the gastrointestinal tract, thereby inhibiting the subsequent development of oxidative stress in the systemic circulation. In addition, the long-term ingestion of chitosan has the potential for use in treating hyperphosphatemia in hemodialysis patients.
Subject(s)
Chitosan/pharmacology , Oxidative Stress/drug effects , Renal Dialysis/adverse effects , Aged , Antioxidants/metabolism , Antioxidants/pharmacology , Chitosan/metabolism , Humans , Hyperphosphatemia/drug therapy , Indican/blood , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Middle Aged , Phosphates/metabolism , Serum Albumin/metabolism , Treatment OutcomeABSTRACT
The degree of oxidized cysteine (Cys) 34 in human serum albumin (HSA), as determined by high performance liquid chromatography (HPLC), is correlated with oxidative stress related pathological conditions. In order to further characterize the oxidation of Cys34-HSA at the molecular level and to develop a suitable analytical method for a rapid and sensitive clinical laboratory analysis, the use of electrospray ionization time-of-flight mass spectrometer (ESI-TOFMS) was evaluated. A marked increase in the cysteinylation of Cys34 occurs in chronic liver and kidney diseases and diabetes mellitus. A significant positive correlation was observed between the Cys-Cys34-HSA fraction of plasma samples obtained from 229 patients, as determined by ESI-TOFMS, and the degree of oxidized Cys34-HSA determined by HPLC. The Cys-Cys34-HSA fraction was significantly increased with the progression of liver cirrhosis, and was reduced by branched chain amino acids (BCAA) treatment. The changes in the Cys-Cys34-HSA fraction were significantly correlated with the alternations of the plasma levels of advanced oxidized protein products, an oxidative stress marker for proteins. The binding ability of endogenous substances (bilirubin and tryptophan) and drugs (warfarin and diazepam) to HSA purified from chronic liver disease patients were significantly suppressed but significantly improved by BCAA supplementation. Interestingly, the changes in this physiological function of HSA in chronic liver disease were correlated with the Cys-Cys34-HSA fraction. In conclusion, ESI-TOFMS is a suitable high throughput method for the rapid and sensitive quantification of Cys-Cys34-HSA in a large number of samples for evaluating oxidative stress related chronic disease progression or in response to a treatment.