Innate Immune Responses and Antioxidant/Oxidant Imbalance Are Major Determinants of Human Chagas Disease

dc.contributor.authorDhiman, Monisha
dc.contributor.authorCoronado, Yun A.
dc.contributor.authorVallejo, Cecillia K.
dc.contributor.authorPeterson, John R.
dc.contributor.authorEjilemele, Adetoun
dc.contributor.authorNunez, Sonia
dc.contributor.authorZago, Maria Paola
dc.contributor.authorSpratt, Hiedi
dc.contributor.authorGarg, Nisha Jain
dc.date.accessioned2017-08-12T07:29:12Z
dc.date.accessioned2024-08-14T07:40:34Z
dc.date.available2017-08-12T07:29:12Z
dc.date.available2024-08-14T07:40:34Z
dc.date.issued2013
dc.description.abstractBackground:We investigated the pathological and diagnostic role of selected markers of inflammation, oxidant/antioxidant status, and cellular injury in human Chagas disease.Methods:Seropositive/chagasic subjects characterized as clinically-symptomatic or clinically-asymptomatic (n = 116), seronegative/cardiac subjects (n = 102), and seronegative/healthy subjects (n = 45) were analyzed for peripheral blood biomarkers.Results:Seropositive/chagasic subjects exhibited an increase in sera or plasma levels of myeloperoxidase (MPO, 2.8-fold), advanced oxidation protein products (AOPP, 56%), nitrite (5.7-fold), lipid peroxides (LPO, 12-17-fold) and malondialdehyde (MDA, 4-6-fold); and a decline in superoxide dismutase (SOD, 52%) and glutathione (GSH, 75%) contents. Correlation analysis identified a significant (p<0.001) linear relationship between inflammatory markers (AOPP/nitrite: r = 0.877), inflammation and antioxidant/oxidant status (AOPP/glutathione peroxidase (GPX): r = 0.902, AOPP/GSH: r = 0.806, Nitrite/GPX: 0.773, Nitrite/LPO: 0.805, MDA/MPO: 0.718), and antioxidant/oxidant levels (GPX/MDA: r = 0.768) in chagasic subjects. Of these, MPO, LPO and nitrite biomarkers were highly specific and sensitive for distinguishing seropositive/chagasic subjects from seronegative/healthy controls (p<0.001, training and fitting AUC/ROC >0.95). The MPO (r = 0.664) and LPO (r = 0.841) levels were also correlated with clinical disease state in chagasic subjects (p<0.001). Seronegative/cardiac subjects exhibited up to 77% decline in SOD, 3-5-fold increase in LPO and glutamate pyruvate transaminase (GPT) levels, and statistically insignificant change in MPO, AOPP, MDA, GPX, GSH, and creatine kinase (CK) levels.Conclusions:The interlinked effects of innate immune responses and antioxidant/oxidant imbalance are major determinants of human Chagas disease. The MPO, LPO and nitrite are excellent biomarkers for diagnosing seropositive/chagasic subjects, and MPO and LPO levels have potential utility in identifying clinical severity of Chagas disease. ? 2013 Dhiman et al.en_US
dc.identifier.citationDhiman, M., Coronado, Y. A., Vallejo, C. K., Petersen, J. R., Ejilemele, A., Nu?ez, S., . . . Garg, N. J. (2013). Innate Immune Responses and Antioxidant/Oxidant Imbalance Are Major Determinants of Human Chagas Disease. PLoS Neglected Tropical Diseases, 7(8). doi: 10.1371/journal.pntd.0002364en_US
dc.identifier.doi10.1371/journal.pntd.0002364
dc.identifier.issn19352727
dc.identifier.urihttps://kr.cup.edu.in/handle/32116/334
dc.identifier.urlhttp://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002364
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.subjectAlanine Aminotransferaseen_US
dc.subjectAntioxidanten_US
dc.subjectBiological Markeren_US
dc.subjectGlutathioneen_US
dc.subjectMyeloperoxidaseen_US
dc.subjectOxidizing Agenten_US
dc.subjectSuperoxide Dismutaseen_US
dc.subjectAdulten_US
dc.subjectCell Damageen_US
dc.subjectChagas Diseaseen_US
dc.subjectControlled Studyen_US
dc.subjectDisease Markeren_US
dc.subjectFemaleen_US
dc.subjectHumanen_US
dc.subjectInflammationen_US
dc.subjectInnate Immunityen_US
dc.subjectMajor Clinical Studyen_US
dc.subjectMaleen_US
dc.subjectOxidative Stressen_US
dc.titleInnate Immune Responses and Antioxidant/Oxidant Imbalance Are Major Determinants of Human Chagas Diseaseen_US
dc.title.journalPLoS Neglected Tropical Diseases
dc.typeArticleen_US
dc.type.accesstypeOpen Accessen_US

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