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Patients with severe malaria also often present thrombocytopenia, and the use of acetylsalicylic acid (ASA), a commonly used non-steroidal anti-inflammatory drug with immunomodulatory and antiplatelet effects, may pose a risk in regions where malaria is endemic. Thus, this study aimed to investigate the systemic impact of ASA and dihydroartemisinin (DHA) on ALI induced in mice by\n                      <jats:italic>Plasmodium berghei<\/jats:italic>\n                      NK65 (\n                      <jats:italic>Pb<\/jats:italic>\n                      NK65).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      C57BL\/6 mice were randomly divided into control (C) and\n                      <jats:italic>Pb<\/jats:italic>\n                      NK65 infected groups and were inoculated with uninfected or 10\n                      <jats:sup>4<\/jats:sup>\n                      infected erythrocytes, respectively. Then, the animals were treated with DHA (3\u00a0mg\/kg) or vehicle (DMSO) at the 8-day post-infection (dpi) for 7\u00a0days and with ASA (100\u00a0mg\/kg, single dose), and analyses were performed at 9 or 15 dpi. Lung mechanics were performed, and lungs were collected for oedema evaluation and histological analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Pb<\/jats:italic>\n                      NK65 infection led to lung oedema, as well as increased lung static elastance (Est, L), resistive (\u0394P1, L) and viscoelastic (\u0394P2, L) pressures, percentage of mononuclear cells, inflammatory infiltrate, hemorrhage, alveolar oedema, and alveolar thickening septum at 9 dpi. Mice that received DHA or DHA\u2009+\u2009ASA had an increase in Est, L, and CD36 expression on inflammatory monocytes and higher protein content on bronchoalveolar fluid (BALF). However, only the DHA-treated group presented a percentage of inflammatory monocytes similar to the control group and a decrease in \u0394P1, L and \u0394P2, L compared to Pb\u2009+\u2009DMSO. Also, combined treatment with DHA\u2009+\u2009ASA led to an impairment in diffuse alveolar damage score and lung function at 9 dpi.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Therapy with ASA maintained lung morpho-functional impairment triggered by\n                      <jats:italic>Pb<\/jats:italic>\n                      NK65 infection, leading to a large influx of inflammatory monocytes to the lung tissue. Based on its deleterious effects in experimental MA-ALI, ASA administration or its treatment maintenance might be carefully reconsidered and further investigated in human malaria cases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12936-024-05017-7","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T14:02:34Z","timestamp":1726754554000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Acetylsalicylic acid and dihydroartemisinin combined therapy on experimental malaria-associated acute lung injury: analysis of lung function and the inflammatory process"],"prefix":"10.1186","volume":"23","author":[{"given":"Helena D\u2019Anuncia\u00e7\u00e3o","family":"de Oliveira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Nunes","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiara Nascimento","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Amanda Barbosa Rangel","family":"dos Passos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Jose Rocha Xavier","family":"Freitas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnatas Dutra","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora Gon\u00e7alves","family":"Xisto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Vin\u00edcius","family":"Rangel-Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Pelajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Rieken Macedo","family":"Rocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via Lima","family":"Ribeiro-Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo Caire","family":"de Castro Faria-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Maron-Gutierrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,19]]},"reference":[{"key":"5017_CR1","doi-asserted-by":"publisher","first-page":"733","DOI":"10.4269\/ajtmh.17-0131","volume":"97","author":"F Val","year":"2017","unstructured":"Val F, Machado K, Barbosa L, Salinas JL, Siqueira AM, Alecrim MGC, et al. 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