Protein Carbonyl as a Biomarker of Oxidative Stress in Severe Leptospirosis, and Its Usefulness in Differentiating Leptospirosis from Dengue Infections

Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in dis...

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Published in:PloS one 2016-06, Vol.11 (6), p.e0156085-e0156085
Main Authors: Fernando, Narmada, Wickremesinghe, Shalini, Niloofa, Roshan, Rodrigo, Chaturaka, Karunanayake, Lilani, de Silva, H Janaka, Wickremesinghe, A R, Premawansa, Sunil, Rajapakse, Senaka, Handunnetti, Shiroma M
Format: Article
Language:English
Subjects:
Acids
Adult
Antioxidants
Antioxidants - metabolism
Bilirubin
Biochemistry
Bioindicators
Biological markers
Biology and Life Sciences
Biomarkers
Biomarkers - blood
Biotechnology
Carbonyls
Case-Control Studies
Cytokines
Damage assessment
Damage detection
Dengue
Dengue - blood
Dengue - diagnosis
Dengue - virology
Dengue fever
Dengue Virus - isolation & purification
Development and progression
Diagnosis
Diagnosis, Differential
Disease
Disease control
Epidemics
Fatty acids
Female
Health aspects
Humans
Immune response
Infections
Laboratories
Leptospira
Leptospira - isolation & purification
Leptospirosis
Leptospirosis - blood
Leptospirosis - diagnosis
Leptospirosis - microbiology
Lipid peroxidation
Lipids
Male
Medicine
Medicine and Health Sciences
Molecular biology
Mortality
Nitrates
Nitric oxide
Oxidation
Oxidative Stress
Pathogenesis
Pathogens
Patients
Physical Sciences
Protein Carbonylation
Proteins
Risk factors
Sepsis
Serum proteins
Tropical diseases
Uric acid
Vector-borne diseases
Viral diseases
Zoonoses
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creator Fernando, Narmada
Wickremesinghe, Shalini
Niloofa, Roshan
Rodrigo, Chaturaka
Karunanayake, Lilani
de Silva, H Janaka
Wickremesinghe, A R
Premawansa, Sunil
Rajapakse, Senaka
Handunnetti, Shiroma M
description Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p
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Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p&lt;0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p&lt;0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p&lt;0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p&lt;0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to save lives via prompt patient management.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0156085</identifier><identifier>PMID: 27280281</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Adult ; Antioxidants ; Antioxidants - metabolism ; Bilirubin ; Biochemistry ; Bioindicators ; Biological markers ; Biology and Life Sciences ; Biomarkers ; Biomarkers - blood ; Biotechnology ; Carbonyls ; Case-Control Studies ; Cytokines ; Damage assessment ; Damage detection ; Dengue ; Dengue - blood ; Dengue - diagnosis ; Dengue - virology ; Dengue fever ; Dengue Virus - isolation &amp; purification ; Development and progression ; Diagnosis ; Diagnosis, Differential ; Disease ; Disease control ; Epidemics ; Fatty acids ; Female ; Health aspects ; Humans ; Immune response ; Infections ; Laboratories ; Leptospira ; Leptospira - isolation &amp; purification ; Leptospirosis ; Leptospirosis - blood ; Leptospirosis - diagnosis ; Leptospirosis - microbiology ; Lipid peroxidation ; Lipids ; Male ; Medicine ; Medicine and Health Sciences ; Molecular biology ; Mortality ; Nitrates ; Nitric oxide ; Oxidation ; Oxidative Stress ; Pathogenesis ; Pathogens ; Patients ; Physical Sciences ; Protein Carbonylation ; Proteins ; Risk factors ; Sepsis ; Serum proteins ; Tropical diseases ; Uric acid ; Vector-borne diseases ; Viral diseases ; Zoonoses</subject><ispartof>PloS one, 2016-06, Vol.11 (6), p.e0156085-e0156085</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Fernando et al. 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purification</subject><subject>Leptospirosis</subject><subject>Leptospirosis - blood</subject><subject>Leptospirosis - diagnosis</subject><subject>Leptospirosis - microbiology</subject><subject>Lipid peroxidation</subject><subject>Lipids</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Molecular biology</subject><subject>Mortality</subject><subject>Nitrates</subject><subject>Nitric oxide</subject><subject>Oxidation</subject><subject>Oxidative Stress</subject><subject>Pathogenesis</subject><subject>Pathogens</subject><subject>Patients</subject><subject>Physical Sciences</subject><subject>Protein Carbonylation</subject><subject>Proteins</subject><subject>Risk factors</subject><subject>Sepsis</subject><subject>Serum proteins</subject><subject>Tropical diseases</subject><subject>Uric acid</subject><subject>Vector-borne diseases</subject><subject>Viral diseases</subject><subject>Zoonoses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99qFDEUxgdRbK2-gWigIArumklmksmNUFv_LBQqtnobMpmTbepssiaZ0j6Jr2u2nZaOFJS5yJD8zpeT75xTFM9LPC8pL9-d-SE41c_X3sEclzXDTf2g2C4FJTNGMH1453-reBLjGcY1bRh7XGwRThpMmnK7-P01-ATWoX0VWu8ue6QiUuiD9SsVfkJA3qCjC9upZM8BHacAMaKMH8M5BECHsE4-rm3w0ca3SLkOLVJE3yOYoXcje2CNybBLNqu45TQImeBX6ADccgC0cAZ0st7Fp8Ujo_oIz8Z1pzj59PFk_8vs8OjzYn_vcKa5KNOMd63RirVEA2Yt7YRpRac46zimLeE1aN3k45JWGAOtjGKMVZywHNSpTtOd4uW17Lr3UY6WRllyUVeNqBnPxOKa6Lw6k-tgsy-X0isrrzZ8WEoVktU9SK6woLwhhFaqEg3JqWlFS9Y1wAUmm9vej7cN7Qo6nS0Jqp-ITk-cPZVLfy4rkWtHqizwehQI_tcAMcmVjRr6XjnwQ867wQ0nggnxbzQ_MbOUlBnd_Qu934iRWqr8VuuMzynqjajcq-qK8WzxRmt-D5W_DlZW51Y1Nu9PAt5MAjKT4CIt1RCjXBx_-3_26MeUfXWHPQXVp9Po--Gqu6ZgdQ3q3I8xgLmtR4nlZtJu3JCbSZPjpOWwF3dreRt0M1r0D0lBJg4</recordid><startdate>20160609</startdate><enddate>20160609</enddate><creator>Fernando, Narmada</creator><creator>Wickremesinghe, Shalini</creator><creator>Niloofa, Roshan</creator><creator>Rodrigo, Chaturaka</creator><creator>Karunanayake, Lilani</creator><creator>de Silva, H Janaka</creator><creator>Wickremesinghe, A R</creator><creator>Premawansa, Sunil</creator><creator>Rajapakse, Senaka</creator><creator>Handunnetti, Shiroma M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5899-9564</orcidid></search><sort><creationdate>20160609</creationdate><title>Protein Carbonyl as a Biomarker of Oxidative Stress in Severe Leptospirosis, and Its Usefulness in Differentiating Leptospirosis from Dengue Infections</title><author>Fernando, Narmada ; 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purification</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Diagnosis, Differential</topic><topic>Disease</topic><topic>Disease control</topic><topic>Epidemics</topic><topic>Fatty acids</topic><topic>Female</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Immune response</topic><topic>Infections</topic><topic>Laboratories</topic><topic>Leptospira</topic><topic>Leptospira - isolation &amp; purification</topic><topic>Leptospirosis</topic><topic>Leptospirosis - blood</topic><topic>Leptospirosis - diagnosis</topic><topic>Leptospirosis - microbiology</topic><topic>Lipid peroxidation</topic><topic>Lipids</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Molecular biology</topic><topic>Mortality</topic><topic>Nitrates</topic><topic>Nitric oxide</topic><topic>Oxidation</topic><topic>Oxidative Stress</topic><topic>Pathogenesis</topic><topic>Pathogens</topic><topic>Patients</topic><topic>Physical Sciences</topic><topic>Protein Carbonylation</topic><topic>Proteins</topic><topic>Risk factors</topic><topic>Sepsis</topic><topic>Serum proteins</topic><topic>Tropical diseases</topic><topic>Uric acid</topic><topic>Vector-borne diseases</topic><topic>Viral diseases</topic><topic>Zoonoses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fernando, Narmada</creatorcontrib><creatorcontrib>Wickremesinghe, Shalini</creatorcontrib><creatorcontrib>Niloofa, Roshan</creatorcontrib><creatorcontrib>Rodrigo, Chaturaka</creatorcontrib><creatorcontrib>Karunanayake, Lilani</creatorcontrib><creatorcontrib>de Silva, H Janaka</creatorcontrib><creatorcontrib>Wickremesinghe, A R</creatorcontrib><creatorcontrib>Premawansa, Sunil</creatorcontrib><creatorcontrib>Rajapakse, Senaka</creatorcontrib><creatorcontrib>Handunnetti, Shiroma M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints In Context</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; 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Fisheries Abstracts (ASFA) 1: Biological Sciences &amp; Living Resources</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) 3: Aquatic Pollution &amp; Environmental Quality</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) Professional</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fernando, Narmada</au><au>Wickremesinghe, Shalini</au><au>Niloofa, Roshan</au><au>Rodrigo, Chaturaka</au><au>Karunanayake, Lilani</au><au>de Silva, H Janaka</au><au>Wickremesinghe, A R</au><au>Premawansa, Sunil</au><au>Rajapakse, Senaka</au><au>Handunnetti, Shiroma M</au><au>Khodarahmi, Reza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protein Carbonyl as a Biomarker of Oxidative Stress in Severe Leptospirosis, and Its Usefulness in Differentiating Leptospirosis from Dengue Infections</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-06-09</date><risdate>2016</risdate><volume>11</volume><issue>6</issue><spage>e0156085</spage><epage>e0156085</epage><pages>e0156085-e0156085</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p&lt;0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p&lt;0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p&lt;0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p&lt;0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to save lives via prompt patient management.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27280281</pmid><doi>10.1371/journal.pone.0156085</doi><orcidid>https://orcid.org/0000-0001-5899-9564</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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1932-6203
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subjects Acids
Adult
Antioxidants
Antioxidants - metabolism
Bilirubin
Biochemistry
Bioindicators
Biological markers
Biology and Life Sciences
Biomarkers
Biomarkers - blood
Biotechnology
Carbonyls
Case-Control Studies
Cytokines
Damage assessment
Damage detection
Dengue
Dengue - blood
Dengue - diagnosis
Dengue - virology
Dengue fever
Dengue Virus - isolation & purification
Development and progression
Diagnosis
Diagnosis, Differential
Disease
Disease control
Epidemics
Fatty acids
Female
Health aspects
Humans
Immune response
Infections
Laboratories
Leptospira
Leptospira - isolation & purification
Leptospirosis
Leptospirosis - blood
Leptospirosis - diagnosis
Leptospirosis - microbiology
Lipid peroxidation
Lipids
Male
Medicine
Medicine and Health Sciences
Molecular biology
Mortality
Nitrates
Nitric oxide
Oxidation
Oxidative Stress
Pathogenesis
Pathogens
Patients
Physical Sciences
Protein Carbonylation
Proteins
Risk factors
Sepsis
Serum proteins
Tropical diseases
Uric acid
Vector-borne diseases
Viral diseases
Zoonoses
title Protein Carbonyl as a Biomarker of Oxidative Stress in Severe Leptospirosis, and Its Usefulness in Differentiating Leptospirosis from Dengue Infections
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