ArticlePLoS neglected tropical diseases2018
Manganese superoxide dismutase deficiency exacerbates the mitochondrial ROS production and oxidative damage in Chagas disease.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- An Integrated Analysis of Manganese Metabolism-Related Genes and Their Association With Biomarkers, Immune Infiltration, and Clinical Subtypes in Alzheimer's Disease.Genes, brain, and behavior · 2026Article
- A New Nitroimidazole-Based Drug Attenuates Skeletal Myositis and Overcomes Benznidazole Resistance in Experimental Chagas Disease.ACS pharmacology & translational science · 2026Article
- Harpagide attenuates cerebral ischemic injury by modulating mitochondrial calcium homeostasis associated with the AMPK-MCU axis.Scientific reports · 2026Article
- Superoxide Dismutases in Immune Regulation and Infectious Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Mitochondrial Transplantation: A Paradigm Shift in Osteoporosis Therapy.International journal of nanomedicine · 2025Review
- Cardiac and Digestive Forms of Chagas Disease: An Update on Pathogenesis, Genetics, and Therapeutic Targets.Mediators of inflammation · 2025Review
- Animal models for exploring Chagas disease pathogenesis and supporting drug discovery.Clinical microbiology reviews · 2024Review
- Small molecule mediators of host-T. cruzi-environment interactions in Chagas disease.PLoS pathogens · 2024Review
- Mn(III) Porphyrin, MnTnBuOE-2-PyPInternational journal of molecular sciences · 2023Article
- Erythrocytic, Enzymatic, and Histological Markers of Oxidative Stress in Subacute and Chronic Stage Infections in Wistar Rats (Disease markers · 2023Article
- Electrophilic Aldehyde 4-Hydroxy-2-Nonenal Mediated Signaling and Mitochondrial Dysfunction.Biomolecules · 2022Review
- Air Pollution's Impact on Cardiac Remodeling in an Experimental Model of Chagas Cardiomyopathy.Frontiers in cellular and infection microbiology · 2022Article
- Multi-therapeutic strategy targeting parasite and inflammation-related alterations to improve prognosis of chronic Chagas cardiomyopathy: a hypothesis-based approach.Memorias do Instituto Oswaldo Cruz · 2022Article
- The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease.Antioxidants (Basel, Switzerland) · 2021Review
- The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies.International journal of molecular sciences · 2021Review
- Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway.International journal of molecular sciences · 2021Article
- Effect of Mitochondrial Antioxidant (Mito-TEMPO) on Burn-Induced Cardiac Dysfunction.Journal of the American College of Surgeons · 2021Article
- Cryptotanshinone Ameliorates Doxorubicin-Induced Cardiotoxicity by Targeting Akt-GSK-3β-mPTP Pathway In Vitro.Molecules (Basel, Switzerland) · 2021Article
- Physical Exercise Promotes a Reduction in Cardiac Fibrosis in the Chronic Indeterminate Form of Experimental Chagas Disease.Frontiers in immunology · 2021Article
- Ultrathin gold nanowires to enhance radiation therapy.Journal of nanobiotechnology · 2020Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
In this study, we have investigated the effects of manganese superoxide dismutase (SOD2 or MnSOD) deficiency on mitochondrial function and oxidative stress during Chagas disease. For this, C57BL/6 wild type (WT) and MnSOD+/- mice were infected with Trypanosoma cruzi (Tc), and evaluated at 150 days' post-infection that corresponded to chronic disease phase. Genetic deletion of SOD2 decreased the expression and activity of MnSOD, but it had no effect on the expression of other members of the SOD family. The myocardial expression and activity of MnSOD were significantly decreased in chronically infected WT mice, and it was further worsened in MnSOD+/- mice. Chronic T. cruzi infection led to a decline in mitochondrial complex I and complex II driven, ADP-coupled respiration and ATP synthesis in the myocardium of WT mice. The baseline oxidative phosphorylation (OXPHOS) capacity in MnSOD+/- mice was decreased, and it had an additive effect on mitochondrial dysregulation of ATP synthesis capacity in chagasic myocardium. Further, MnSOD deficiency exacerbated the mitochondrial rate of reactive oxygen species (ROS) production and myocardial oxidative stress (H2O2, protein carbonyls, malondialdehyde, and 4-hydroxynonenal) in Chagas disease. Peripheral and myocardial parasite burden and inflammatory response (myeloperoxidase, IL-6, lactate dehydrogenase, inflammatory infiltrate) were increased in all chagasic WT and MnSOD+/- mice. We conclude that MnSOD deficiency exacerbates the loss in mitochondrial function and OXPHOS capacity and enhances the myocardial oxidative damage in chagasic cardiomyopathy. Mitochondria targeted, small molecule mitigators of MnSOD deficiency will offer potential benefits in averting the mitochondrial dysfunction and chronic oxidative stress in Chagas disease.
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