{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:31:30Z","timestamp":1790659890269,"version":"4.1.0"},"reference-count":87,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T00:00:00Z","timestamp":1745107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica (PAPIIT)","award":["IN228620"],"award-info":[{"award-number":["IN228620"]}]},{"name":"Programa de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica (PAPIIT)","award":["IN223524"],"award-info":[{"award-number":["IN223524"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malaria, the deadliest parasitic disease in the world, is sexually dimorphic, inflammatory, and oxidative. Males experience more severe symptoms and mortality than females do; therefore, the roles of 17\u03b2-estradiol and testosterone in this phenomenon have been studied. Both hormones affect oxidative stress, the primary mechanism of Plasmodium elimination. Estradiol has antioxidant activity, but the role of testosterone is controversial. Testosterone increases oxidative stress by reducing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities, which increase lipoperoxidation in the testis. However, the antioxidant properties of testosterone in prostate and nervous tissue have also been reported. The discrepancies are probably because when testosterone levels increase, the aromatase enzyme transforms testosterone into estrogens that possess antioxidant activity, which masks the results. Therefore, it is unknown whether testosterone is involved in the sexual dimorphism that occurs in oxidative stress in malaria. In this work, we administered testosterone and simultaneously inhibited aromatase with letrozole to evaluate the role of testosterone in the sexually dimorphic pattern of oxidative stress that occurs in the blood, spleen, and brain of male and female CBA\/Ca mice infected with Plasmodium berghei ANKA (P. berghei ANKA). Testosterone triggers parasitemia in males, who also display more oxidative stress than females in the absence of infection, leading to sexually dimorphic patterns. Interestingly, increasing testosterone levels in infected mice reduced oxidative stress in males and increased oxidative stress in females, reversing or eliminating the dimorphic patterns observed. Oxidative stress varies in each tissue; the brain was the most protected, while the blood was the greatest damaged. Our findings highlight the role of testosterone as a regulator of oxidative stress in a tissue and sex-specific manner; therefore, understanding the role of testosterone in malaria may contribute to the development of sex-specific personalized antimalarial therapies.<\/jats:p>","DOI":"10.3390\/ijms26083898","type":"journal-article","created":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T20:24:16Z","timestamp":1745180656000},"page":"3898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Testosterone Modulates Oxidative Stress in a Sexually Dimorphic Manner in CBA\/Ca Mice Infected with Plasmodium berghei ANKA"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8134-833X","authenticated-orcid":false,"given":"Teresita de Jes\u00fas","family":"Nolasco-P\u00e9rez","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda en Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad de M\u00e9xico 09320, CP, Mexico"},{"name":"Posgrado en Ciencias Biol\u00f3gicas, Unidad de Posgrado, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Circuito de Posgrados, Ciudad Universitaria, Ciudad de M\u00e9xico 04510, CP, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor Hugo","family":"Salazar-Casta\u00f1\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda en Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad de M\u00e9xico 09320, CP, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Antonio","family":"Cervantes-Candelas","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda en Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad de M\u00e9xico 09320, CP, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fidel Orlando","family":"Buend\u00eda-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda en Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad de M\u00e9xico 09320, CP, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8499-6439","authenticated-orcid":false,"given":"Jes\u00fas","family":"Aguilar-Castro","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda en Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad de M\u00e9xico 09320, CP, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-7365","authenticated-orcid":false,"given":"Martha","family":"Legorreta-Herrera","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda en Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Ciudad de M\u00e9xico 09320, CP, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,20]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023). 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