{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:24:39Z","timestamp":1790061879997,"version":"4.0.1"},"reference-count":47,"publisher":"Cambridge University Press (CUP)","issue":"11","license":[{"start":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T00:00:00Z","timestamp":1498176000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["www.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>American tegumentary leishmaniasis is caused by different species of<jats:italic>Leishmania.<\/jats:italic>This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of<jats:italic>Crotalus durissus terrificus<\/jats:italic>venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage \u2013<jats:italic>Leishmania<\/jats:italic>interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage<jats:italic>M1<\/jats:italic>polarization during<jats:italic>Leishmania<\/jats:italic>infection murine macrophages,<jats:italic>Leishmania amazonensis<\/jats:italic>promastigotes and<jats:italic>L. amazonensis<\/jats:italic>-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC<jats:sub>50<\/jats:sub>= 22\u00b786<jats:italic>\u00b5<\/jats:italic>g mL<jats:sup>\u22121<\/jats:sup>) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with<jats:italic>Leishmania<\/jats:italic>, macrophages exhibited an increase in nitric oxide production that converged into an<jats:italic>M1<\/jats:italic>activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-\u03b1 and changes in their morphology. CTX was able to reverse the<jats:italic>L. amazonensis<\/jats:italic>-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the<jats:italic>M1<\/jats:italic>profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment.<\/jats:p>","DOI":"10.1017\/s0031182017000944","type":"journal-article","created":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T06:25:46Z","timestamp":1498199146000},"page":"1458-1467","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":18,"title":["Crotoxin stimulates an<i>M1<\/i>activation profile in murine macrophages during<i>Leishmania amazonensis<\/i>infection"],"prefix":"10.1017","volume":"144","author":[{"given":"L. H. S.","family":"FARIAS","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. P. 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