The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease
Chagas disease is a neglected tropical disease caused by the flagellated protozoa <i>Trypanosome cruzi</i>. This illness affects to almost 8–12 million people worldwide, however, is endemic to Latin American countries. It is mainly vectorially transmitted by insects of the Triatominae fa...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/7/1022 |
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| author | Edio Maldonado Diego A. Rojas Fabiola Urbina Aldo Solari |
| author_facet | Edio Maldonado Diego A. Rojas Fabiola Urbina Aldo Solari |
| author_sort | Edio Maldonado |
| collection | DOAJ |
| description | Chagas disease is a neglected tropical disease caused by the flagellated protozoa <i>Trypanosome cruzi</i>. This illness affects to almost 8–12 million people worldwide, however, is endemic to Latin American countries. It is mainly vectorially transmitted by insects of the Triatominae family, although other transmission routes also exist. <i>T. cruzi</i>-infected cardiomyocytes at the chronic stage of the disease display severe mitochondrial dysfunction and high ROS production, leading to chronic myocardial inflammation and heart failure. Under cellular stress, cells usually can launch mitochondrial biogenesis in order to restore energy loss. Key players to begin mitochondrial biogenesis are the PGC-1 (PPARγ coactivator 1) family of transcriptional coactivators, which are activated in response to several stimuli, either by deacetylation or dephosphorylation, and in turn can serve as coactivators for the NRF (nuclear respiratory factor) family of transcription factors. The NRF family of transcriptional activators, namely NRF1 and NRF2, can activate gene expression of oxidative phosphorylation (OXPHOS) components, mitochondrial transcriptional factor (Tfam) and nuclear encoded mitochondrial proteins, leading to mitochondrial biogenesis. On the other hand, NRF2 can activate gene expression of antioxidant enzymes in response to antioxidants, oxidants, electrophile compounds, pharmaceutical and dietary compounds in a mechanism dependent on KEAP1 (Kelch-like ECH-associated protein 1). Since a definitive cure to treat Chagas disease has not been found yet; the use of antioxidants a co-adjuvant therapy has been proposed in an effort to improve mitochondrial functions, biogenesis, and the antioxidant defenses response. Those antioxidants could activate different pathways to begin mitochondrial biogenesis and/or cytoprotective antioxidant defenses. In this review we discuss the main mechanisms of mitochondrial biogenesis and the NRF2-KEAP1 activation pathway. We also reviewed the antioxidants used as co-adjuvant therapy to treat experimental Chagas disease and their action mechanisms and finish with the discussion of antioxidant therapy used in Chagas disease patients. |
| first_indexed | 2024-03-10T10:03:58Z |
| format | Article |
| id | doaj.art-cfde0ff8f4d24f1bbce1fa60b76b462b |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T10:03:58Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-cfde0ff8f4d24f1bbce1fa60b76b462b2023-11-22T01:42:32ZengMDPI AGAntioxidants2076-39212021-06-01107102210.3390/antiox10071022The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas DiseaseEdio Maldonado0Diego A. Rojas1Fabiola Urbina2Aldo Solari3Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, ChileInstituto de Ciencias Biomédicas (ICB), Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8380453, ChilePrograma de Biología Celular y Molecular, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, ChilePrograma de Biología Celular y Molecular, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, ChileChagas disease is a neglected tropical disease caused by the flagellated protozoa <i>Trypanosome cruzi</i>. This illness affects to almost 8–12 million people worldwide, however, is endemic to Latin American countries. It is mainly vectorially transmitted by insects of the Triatominae family, although other transmission routes also exist. <i>T. cruzi</i>-infected cardiomyocytes at the chronic stage of the disease display severe mitochondrial dysfunction and high ROS production, leading to chronic myocardial inflammation and heart failure. Under cellular stress, cells usually can launch mitochondrial biogenesis in order to restore energy loss. Key players to begin mitochondrial biogenesis are the PGC-1 (PPARγ coactivator 1) family of transcriptional coactivators, which are activated in response to several stimuli, either by deacetylation or dephosphorylation, and in turn can serve as coactivators for the NRF (nuclear respiratory factor) family of transcription factors. The NRF family of transcriptional activators, namely NRF1 and NRF2, can activate gene expression of oxidative phosphorylation (OXPHOS) components, mitochondrial transcriptional factor (Tfam) and nuclear encoded mitochondrial proteins, leading to mitochondrial biogenesis. On the other hand, NRF2 can activate gene expression of antioxidant enzymes in response to antioxidants, oxidants, electrophile compounds, pharmaceutical and dietary compounds in a mechanism dependent on KEAP1 (Kelch-like ECH-associated protein 1). Since a definitive cure to treat Chagas disease has not been found yet; the use of antioxidants a co-adjuvant therapy has been proposed in an effort to improve mitochondrial functions, biogenesis, and the antioxidant defenses response. Those antioxidants could activate different pathways to begin mitochondrial biogenesis and/or cytoprotective antioxidant defenses. In this review we discuss the main mechanisms of mitochondrial biogenesis and the NRF2-KEAP1 activation pathway. We also reviewed the antioxidants used as co-adjuvant therapy to treat experimental Chagas disease and their action mechanisms and finish with the discussion of antioxidant therapy used in Chagas disease patients.https://www.mdpi.com/2076-3921/10/7/1022<i>Trypanosoma cruzi</i>ROSChagasantioxidantsoxidative stressmitochondrial biogenesis |
| spellingShingle | Edio Maldonado Diego A. Rojas Fabiola Urbina Aldo Solari The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease Antioxidants <i>Trypanosoma cruzi</i> ROS Chagas antioxidants oxidative stress mitochondrial biogenesis |
| title | The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease |
| title_full | The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease |
| title_fullStr | The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease |
| title_full_unstemmed | The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease |
| title_short | The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease |
| title_sort | use of antioxidants as potential co adjuvants to treat chronic chagas disease |
| topic | <i>Trypanosoma cruzi</i> ROS Chagas antioxidants oxidative stress mitochondrial biogenesis |
| url | https://www.mdpi.com/2076-3921/10/7/1022 |
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