Innate Immune Responses and Antioxidant/Oxidant Imbalance Are Major Determinants of Human Chagas Disease
dc.contributor.author | Dhiman, Monisha | |
dc.contributor.author | Coronado, Yun A. | |
dc.contributor.author | Vallejo, Cecillia K. | |
dc.contributor.author | Peterson, John R. | |
dc.contributor.author | Ejilemele, Adetoun | |
dc.contributor.author | Nunez, Sonia | |
dc.contributor.author | Zago, Maria Paola | |
dc.contributor.author | Spratt, Hiedi | |
dc.contributor.author | Garg, Nisha Jain | |
dc.date.accessioned | 2017-08-12T07:29:12Z | |
dc.date.accessioned | 2024-08-14T07:40:34Z | |
dc.date.available | 2017-08-12T07:29:12Z | |
dc.date.available | 2024-08-14T07:40:34Z | |
dc.date.issued | 2013 | |
dc.description.abstract | Background: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.citation | Dhiman, 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.0002364 | en_US |
dc.identifier.doi | 10.1371/journal.pntd.0002364 | |
dc.identifier.issn | 19352727 | |
dc.identifier.uri | https://kr.cup.edu.in/handle/32116/334 | |
dc.identifier.url | http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002364 | |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.subject | Alanine Aminotransferase | en_US |
dc.subject | Antioxidant | en_US |
dc.subject | Biological Marker | en_US |
dc.subject | Glutathione | en_US |
dc.subject | Myeloperoxidase | en_US |
dc.subject | Oxidizing Agent | en_US |
dc.subject | Superoxide Dismutase | en_US |
dc.subject | Adult | en_US |
dc.subject | Cell Damage | en_US |
dc.subject | Chagas Disease | en_US |
dc.subject | Controlled Study | en_US |
dc.subject | Disease Marker | en_US |
dc.subject | Female | en_US |
dc.subject | Human | en_US |
dc.subject | Inflammation | en_US |
dc.subject | Innate Immunity | en_US |
dc.subject | Major Clinical Study | en_US |
dc.subject | Male | en_US |
dc.subject | Oxidative Stress | en_US |
dc.title | Innate Immune Responses and Antioxidant/Oxidant Imbalance Are Major Determinants of Human Chagas Disease | en_US |
dc.title.journal | PLoS Neglected Tropical Diseases | |
dc.type | Article | en_US |
dc.type.accesstype | Open Access | en_US |