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      Oxidized human serum albumin as a possible correlation factor for atherosclerosis in a rural Japanese population: the results of the Yakumo Study

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          Abstract

          Background

          The effect of the redox state of human serum albumin (HSA) on the antioxidant properties of the entire body has been a focus of recent research. The usefulness of HSA redox state as a biomarker for reducing oxidative stress has been investigated in clinical settings; however, evidence for its significance as a health index in non-clinical settings is yet to be established. This study aimed to examine the associations between HSA redox state and the atherosclerotic indices of carotid intima-media thickness (IMT) and plaque formation in a rural Japanese population.

          Methods

          We conducted a cross-sectional study as part of a health check-up program in the rural area of Hokkaido, Japan, at the end of August 2013. A total of 281 residents (124 men and 157 women) were included in the final analysis. Lifestyle-related data were obtained through a self-reported questionnaire, and ultrasound examinations were performed to measure IMT and determine plaque formation. The high-performance liquid chromatography postcolumn bromocresol green method was used to separate HSA into human nonmercaptalbumin and human mercaptalbumin (HMA).

          Results

          We found a significant negative relationship between the fraction of HMA [f(HMA)] and IMT (standardized β = − 0.132, p = 0.03). Moreover, f(HMA) was significantly associated with plaque formation ( p < 0.01) with an odds ratio of 0.89 (95% confidence interval, 0.81–0.97) for every 10% increment in f(HMA).

          Conclusions

          We found that the HSA redox state, as determined by f(HMA), was associated with atherosclerotic indices in Japanese subjects. These results suggest that the HSA redox state indicates the risk of developing atherosclerosis.

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          Most cited references22

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          Albumin: biochemical properties and therapeutic potential.

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            Specific antioxidant properties of human serum albumin

            Human serum albumin (HSA) has been used for a long time as a resuscitation fluid in critically ill patients. It is known to exert several important physiological and pharmacological functions. Among them, the antioxidant properties seem to be of paramount importance as they may be implied in the potential beneficial effects that have been observed in the critical care and hepatological settings. The specific antioxidant functions of the protein are closely related to its structure. Indeed, they are due to its multiple ligand-binding capacities and free radical-trapping properties. The HSA molecule can undergo various structural changes modifying its conformation and hence its binding properties and redox state. Such chemical modifications can occur during bioprocesses and storage conditions of the commercial HSA solutions, resulting in heterogeneous solutions for infusion. In this review, we explore the mechanisms that are responsible for the specific antioxidant properties of HSA in its native form, chemically modified forms, and commercial formulations. To conclude, we discuss the implication of this recent literature for future clinical trials using albumin as a drug and for elucidating the effects of HSA infusion in critically ill patients.
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              Human serum albumin and its relation with oxidative stress.

              Human serum albumin, a negative acute phase reactant and marker of nutritive status, presents at high concentrations in plasma. Albumin has always been used in many clinical states especially to improve circulatory failure. It has been showed that albumin is involved in many bioactive functions such as regulation of plasma osmotic pressure, binding and transport of various endogenous or exogenous compounds, and finally extracellular antioxidant defenses. Molecules like transferrin, caeruloplasmin, haptoglobin, uric acid, bilirubin, alpha-tocopherol, glucose, and albumin constitute extracellular antioxidant defenses in blood plasma but albumin is the most potent one. Most of the antioxidant properties of albumin can be attributed to its unique biochemical structure. The protein possesses antioxidant properties such as binding copper tightly and iron weakly, scavenging free radicals, e.g., hypochlorous acid (HOCl) and Peroxynitrite (ONOOH) and providing thiol group (-SH). Whether it is chronic or acute, during many pathological conditions, biomarkers of oxidative protein damage increase and this observation continues with considerable oxidation of human serum albumin. There is an important necessity to specify its interactions with Reactive Oxygen Species. Generally, it may lower the availability of pro-oxidants and be preferentially oxidized to protect other macromolecules but all these findings make it necessary that researchers give a more detailed explanation of albumin and its relations with oxidative stress.
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                Author and article information

                Contributors
                fujii.ryosuke@j.mbox.nagoya-u.ac.jp
                ueyama@met.nagoya-u.ac.jp
                aoi.arisa@j.mbox.nagoya-u.ac.jp
                ichino@fujita-hu.ac.jp
                kosakabe@fujita-hu.ac.jp
                skeiko@fujita-hu.ac.jp
                ksuzuki@fujita-hu.ac.jp
                nhamajim@med.nagoya-u.ac.jp
                wakai@med.nagoya-u.ac.jp
                +81 52 719 1552 , taka@met.nagoya-u.ac.jp
                Journal
                Environ Health Prev Med
                Environ Health Prev Med
                Environmental Health and Preventive Medicine
                BioMed Central (London )
                1342-078X
                1347-4715
                2 January 2018
                2 January 2018
                2018
                : 23
                : 1
                Affiliations
                [1 ]ISNI 0000 0001 0943 978X, GRID grid.27476.30, Department of Pathophysiological Laboratory Sciences, , Nagoya University Graduate School of Medicine, ; 1-1-20 Daikominami, Higashi-ku, Nagoya, 461-8673 Japan
                [2 ]ISNI 0000 0004 1761 798X, GRID grid.256115.4, Department of Clinical Physiology, , Fujita Health University School of Health Sciences, ; 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192 Japan
                [3 ]ISNI 0000 0004 1761 798X, GRID grid.256115.4, Department of Public Health, , Fujita Health University School of Health Sciences, ; 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192 Japan
                [4 ]ISNI 0000 0001 0943 978X, GRID grid.27476.30, Department of Health Administration, , Nagoya University Graduate School of Medicine, ; 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550 Japan
                [5 ]ISNI 0000 0001 0943 978X, GRID grid.27476.30, Department of Preventive Medicine, , Nagoya University Graduate School of Medicine, ; 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550 Japan
                Article
                690
                10.1186/s12199-017-0690-z
                5748967
                29291718
                c16b1837-60c7-4473-b6f6-1ee00d33085d
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 14 June 2017
                : 18 December 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;
                Award ID: JP26670312
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Occupational & Environmental medicine
                human serum albumin,redox state,carotid intima-media thickness,carotid plaque formation,atherosclerosis,oxidative stress

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