The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection.
Background Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously sho...
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ftdoajarticles:oai:doaj.org/article:1a67838d992942c3894c9ef56f930384 2024-01-14T10:05:07+01:00 The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection. Duc Minh Nguyen Cristina Poveda Jeroen Pollet Fabian Gusovsky Maria Elena Bottazzi Peter J Hotez Kathryn Marie Jones 2023-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011519 https://doaj.org/article/1a67838d992942c3894c9ef56f930384 EN eng Public Library of Science (PLoS) https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011519&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011519 https://doaj.org/article/1a67838d992942c3894c9ef56f930384 PLoS Neglected Tropical Diseases, Vol 17, Iss 11, p e0011519 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011519 2023-12-17T01:40:50Z Background Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously showed that combining low dose BNZ with a prototype therapeutic vaccine is a dose sparing strategy that effectively reduced T. cruzi induced cardiac damage. However, the impact of this treatment on liver health is unknown. Therefore, we evaluated several markers of liver health after treatment with low dose BNZ plus the vaccine therapy in comparison to a curative dose of BNZ. Methodology Female BALB/c mice were infected with a bioluminescent T. cruzi H1 clone for approximately 70 days, then randomly divided into groups of 15 mice each. Mice were treated with a 25mg/kg BNZ, 25μg Tc24-C4 protein/ 5μg E6020-SE (Vaccine), 25mg/kg BNZ followed by vaccine, or 100mg/kg BNZ (curative dose). At study endpoints we evaluated hepatomegaly, parasite burden by quantitative PCR, cellular infiltration by histology, and expression of B-cell translocation gene 2(BTG2) and Peroxisome proliferator-activated receptor alpha (PPARα) by RT-PCR. Levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were quantified from serum. Results Curative BNZ treatment significantly reduced hepatomegaly, liver parasite burdens, and the quantity of cellular infiltrate, but significantly elevated serum levels of ALT, AST, and LDH. Low BNZ plus vaccine did not significantly affect hepatomegaly, parasite burdens or the quantity of cellular infiltrate, but only elevated ALT and AST. Low dose BNZ significantly decreased expression of both BTG2 and PPARα, and curative BNZ reduced expression of BTG2 while low BNZ plus vaccine had no impact. Conclusions These data confirm toxicity associated with curative doses of BNZ and suggest that while dose sparing low BNZ plus vaccine treatment does not ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 11 e0011519 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Duc Minh Nguyen Cristina Poveda Jeroen Pollet Fabian Gusovsky Maria Elena Bottazzi Peter J Hotez Kathryn Marie Jones The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously showed that combining low dose BNZ with a prototype therapeutic vaccine is a dose sparing strategy that effectively reduced T. cruzi induced cardiac damage. However, the impact of this treatment on liver health is unknown. Therefore, we evaluated several markers of liver health after treatment with low dose BNZ plus the vaccine therapy in comparison to a curative dose of BNZ. Methodology Female BALB/c mice were infected with a bioluminescent T. cruzi H1 clone for approximately 70 days, then randomly divided into groups of 15 mice each. Mice were treated with a 25mg/kg BNZ, 25μg Tc24-C4 protein/ 5μg E6020-SE (Vaccine), 25mg/kg BNZ followed by vaccine, or 100mg/kg BNZ (curative dose). At study endpoints we evaluated hepatomegaly, parasite burden by quantitative PCR, cellular infiltration by histology, and expression of B-cell translocation gene 2(BTG2) and Peroxisome proliferator-activated receptor alpha (PPARα) by RT-PCR. Levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were quantified from serum. Results Curative BNZ treatment significantly reduced hepatomegaly, liver parasite burdens, and the quantity of cellular infiltrate, but significantly elevated serum levels of ALT, AST, and LDH. Low BNZ plus vaccine did not significantly affect hepatomegaly, parasite burdens or the quantity of cellular infiltrate, but only elevated ALT and AST. Low dose BNZ significantly decreased expression of both BTG2 and PPARα, and curative BNZ reduced expression of BTG2 while low BNZ plus vaccine had no impact. Conclusions These data confirm toxicity associated with curative doses of BNZ and suggest that while dose sparing low BNZ plus vaccine treatment does not ... |
format |
Article in Journal/Newspaper |
author |
Duc Minh Nguyen Cristina Poveda Jeroen Pollet Fabian Gusovsky Maria Elena Bottazzi Peter J Hotez Kathryn Marie Jones |
author_facet |
Duc Minh Nguyen Cristina Poveda Jeroen Pollet Fabian Gusovsky Maria Elena Bottazzi Peter J Hotez Kathryn Marie Jones |
author_sort |
Duc Minh Nguyen |
title |
The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection. |
title_short |
The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection. |
title_full |
The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection. |
title_fullStr |
The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection. |
title_full_unstemmed |
The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection. |
title_sort |
impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic trypanosoma cruzi infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011519 https://doaj.org/article/1a67838d992942c3894c9ef56f930384 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 11, p e0011519 (2023) |
op_relation |
https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011519&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011519 https://doaj.org/article/1a67838d992942c3894c9ef56f930384 |
op_doi |
https://doi.org/10.1371/journal.pntd.0011519 |
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PLOS Neglected Tropical Diseases |
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17 |
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11 |
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e0011519 |
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