{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:16:49Z","timestamp":1784215009311,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011519","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T00:00:00Z","timestamp":1701734400000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Southern Star Medical Research Institute"},{"name":"The Pathology and Histology Core at Baylor College of Medicine","award":["P30 CA125123"],"award-info":[{"award-number":["P30 CA125123"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Chagas disease, chronic infection with\n                      <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                      , 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\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>cruzi<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      Female BALB\/c mice were infected with a bioluminescent\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>cruzi<\/jats:italic>\n                      H1 clone for approximately 70 days, then randomly divided into groups of 15 mice each. Mice were treated with a 25mg\/kg BNZ, 25\u03bcg Tc24-C4 protein\/ 5\u03bcg 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 (PPAR\u03b1) by RT-PCR. Levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were quantified from serum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 PPAR\u03b1, and curative BNZ reduced expression of BTG2 while low BNZ plus vaccine had no impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data confirm toxicity associated with curative doses of BNZ and suggest that while dose sparing low BNZ plus vaccine treatment does not reduce parasite burdens, it better preserves liver health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0011519","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T13:34:20Z","timestamp":1700573660000},"page":"e0011519","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection"],"prefix":"10.1371","volume":"17","author":[{"given":"Duc Minh","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Poveda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Pollet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Gusovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"Bottazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Hotez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8745-1987","authenticated-orcid":true,"given":"Kathryn Marie","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"issue":"9","key":"pntd.0011519.ref001","first-page":"1922","article-title":"CDC\u2014Chagas Disease\u2014Detailed Fact Sheet","volume":"52","author":"PT Cantey","year":"2022","journal-title":"Transfusion"},{"key":"pntd.0011519.ref002","unstructured":"Chagas disease (also known as American trypanosomiasis) [Internet]. 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