P-1765. Identification of Total Oxidant Status and Superoxide Dismutase Activity as Predictors of Chagas Heart Disease in South American Immigrants in Spain

TL;DR

This study identifies Total Oxidant Status and Superoxide Dismutase activity as potential predictors of heart disease in Chagas disease patients among South American immigrants in Spain.

Contribution

The study introduces TOS and SODact as novel biomarkers for differentiating between Chagas disease stages and potential treatment targets.

Findings

TOS levels were significantly higher in Chagas heart disease and non-Chagas heart failure groups compared to healthy controls.

SOD activity was significantly increased in Chagas heart disease compared to all other groups.

Extreme values of TOS and SODact were associated with cardiac complications like arrhythmia and valvulopathy.

Abstract

Chagas disease (caused by Trypanosoma cruzi) is endemic in most Latin American countries and a growing public health concern among immigrants in European countries. The role of oxidative stress (OS; an imbalance between damaging oxidants [ROS] and antioxidant defenses) in acute Chagas disease is well-established. OS is also involved in the pathophysiology of chronic complications, particularly Chagas cardiomyopathy. We compared the association of markers of OS in plasma, serum, urine, erythrocytes and peripheral blood mononuclear cells (PBMCs) with measures of disease severity in South American immigrants and selected controls.Total Oxidant Status (TOS) levels in serum of the different subject groups. Group comparisons were done using ANOVA testing followed by a Tukey post-hoc test. CDIP = Chagas disease - intermediate phase CHD = Chagas heart disease NCHF = non-Chagas heart failure HC = healthy control. * p < 0.05 ** p < 0.01 *** p < 0.001Protein carbonyl (PCO) levels in serum of the different subject groups. Group comparisons were done using ANOVA testing followed by a Tukey post-hoc test. CDIP = Chagas disease - intermediate phase CHD = Chagas heart disease NCHF = non-Chagas heart failure HC = healthy control. * p < 0.05 *** p < 0.001

Total Oxidant Status (TOS) levels in serum of the different subject groups. Group comparisons were done using ANOVA testing followed by a Tukey post-hoc test. CDIP = Chagas disease - intermediate phase CHD = Chagas heart disease NCHF = non-Chagas heart failure HC = healthy control. * p < 0.05 ** p < 0.01 *** p < 0.001

Protein carbonyl (PCO) levels in serum of the different subject groups. Group comparisons were done using ANOVA testing followed by a Tukey post-hoc test. CDIP = Chagas disease - intermediate phase CHD = Chagas heart disease NCHF = non-Chagas heart failure HC = healthy control. * p < 0.05 *** p < 0.001

We enrolled 4 groups of 10 subjects at the Hospital Clínic de Barcelona (Spain): Bolivian or Ecuadorean immigrants with chronic T. cruzi infection in the indeterminate phase (CDIP) or with cardiac damage (CHD), T. cruzi seronegative subjects from endemic countries (HC) and seronegative patients with heart failure (NCHF). We measured 10 biomarkers of OS in plasma (CATact, GPxact, MDA, SODact), serum (PCO, TAS, TOS), urine (8-OHdG), erythrocytes (GSH) or PBMCs (Nrf2) in duplo. Chronic cardiac damage was classified into stages according to international recommendations adapted to Chagas disease by the American Heart Association. Groups were compared using Kruskal-Wallis or ANOVA followed by post-hoc testing.Superoxide dismutase (SOD) activity in plasma of the different subject groups. Group comparisons were done using Kruskal Wallis testing followed by a Dunn's post-hoc test. CDIP = Chagas disease - intermediate phase CHD = Chagas heart disease NCHF = non-Chagas heart failure HC = healthy control. * p < 0.05 ** p < 0.01Glutathione peroxidase (GPx) activity in plasma of the different subject groups. Group comparisons were done using ANOVA testing followed by a Tukey post-hoc test. CDIP = Chagas disease - intermediate phase CHD = Chagas heart disease NCHF = non-Chagas heart failure HC = healthy control. * p < 0.05 ** p < 0.01

Superoxide dismutase (SOD) activity in plasma of the different subject groups. Group comparisons were done using Kruskal Wallis testing followed by a Dunn's post-hoc test. CDIP = Chagas disease - intermediate phase CHD = Chagas heart disease NCHF = non-Chagas heart failure HC = healthy control. * p < 0.05 ** p < 0.01

Glutathione peroxidase (GPx) activity in plasma of the different subject groups. Group comparisons were done using ANOVA testing followed by a Tukey post-hoc test. CDIP = Chagas disease - intermediate phase CHD = Chagas heart disease NCHF = non-Chagas heart failure HC = healthy control. * p < 0.05 ** p < 0.01

Mean TOS levels were higher in CHD and NCHF groups compared to HC and CDIP (9.9 and 12.6 vs. 3.4 and 1.6 µmol H2O2 eq., respectively, shown in image 1). Mean PCO levels were higher in CHD and NCHF compared to HC (3.1 and 3.5 vs. 2.4 nmol/mg protein, image 2). SODact was significantly increased in CHD compared to all other groups (image 3). Other antioxidant enzymes did not follow this trend, although CDIP had higher mean GPxact than HC and NCHF (159 vs. 112 and 91 nmol/min/mL, image 4). Additionally, extreme values of SODact, TOS, PCO and/or GPxact were associated with sinusal disfunction, atrial arrhythmia, valvulopathy and pacemaker rhythm. These associations differed between CHD and NCHF.

These results suggest that not all biomarkers of OS are altered uniformly, but TOS and SODact could be useful to differentiate between CDIP and CHD. Selectively upregulated SODact can be explored as a potential target for treatment options in CHD.

Eduard Solé, MD, Astrazeneca: Advisor/Consultant|Janssen Pharmaceutica: Advisor/Consultant|Novartis: Advisor/Consultant Nina Hermans, PhD, Professor, Tilman: Grant/Research Support

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