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Cell. Infect. Microbiol."],"abstract":"<jats:p>Treatment of leishmaniasis is a challenging subject. Although available, chemotherapy is limited, presenting toxicity and adverse effects. New drugs with antileishmanial activity are being investigated, such as antiparasitic compounds derived from plants. In this work, we investigated the antileishmanial activity of the biflavonoid amentoflavone on the protozoan<jats:italic>Leishmania amazonensis<\/jats:italic>. Although the antileishmanial activity of amentoflavone has already been reported<jats:italic>in vitro<\/jats:italic>, the mechanisms involved in the parasite death, as well as its action<jats:italic>in vivo<\/jats:italic>, remain unknown. Amentoflavone demonstrated activity on intracellular amastigotes in macrophages obtained from BALB\/c mice (IC<jats:sub>50<\/jats:sub>2.3 \u00b1 0.93 \u03bcM). No cytotoxicity was observed and the selectivity index was estimated as greater than 10. Using BALB\/c mice infected with<jats:italic>L. amazonensis<\/jats:italic>we verified the effect of an intralesional treatment with amentoflavone (0.05 mg\/kg\/dose, in a total of 5 doses every 4 days). Parasite quantification demonstrated that amentoflavone reduced the parasite load in treated footpads (46.3% reduction by limiting dilution assay and 56.5% reduction by Real Time Polymerase Chain Reaction). Amentoflavone decreased the nitric oxide production in peritoneal macrophages obtained from treated animals. The treatment also increased the expression of ferritin and decreased iNOS expression at the site of infection. Furthemore, it increased the production of ROS in peritoneal macrophages infected<jats:italic>in vitro<\/jats:italic>. The increase of ROS<jats:italic>in vitro<\/jats:italic>, associated with the reduction of NO and iNOS expression<jats:italic>in vivo<\/jats:italic>, points to the antioxidant\/prooxidant potential of amentoflavone, which may play an important role in the balance between inflammatory and anti-inflammatory patterns at the infection site. Taken together these results suggest that amentoflavone has the potential to be used in the treatment of cutaneous leishmaniasis, working as an ally in the control and development of the lesion.<\/jats:p>","DOI":"10.3389\/fcimb.2021.615814","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T15:16:20Z","timestamp":1614266180000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Amentoflavone as an Ally in the Treatment of Cutaneous Leishmaniasis: Analysis of Its Antioxidant\/Prooxidant Mechanisms"],"prefix":"10.3389","volume":"11","author":[{"given":"Yasmin Silva","family":"Rizk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandy","family":"Santos-Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiza","family":"Gervazoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiana de Jesus","family":"Hardoim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fl\u00e1via de Oliveira","family":"Cardoso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celeste da Silva Freitas","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Pelajo-Machado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Alexandre","family":"Carollo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla Cardozo Pinto","family":"de Arruda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elmo Eduardo","family":"Almeida-Amaral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T\u00e2nia","family":"Zaverucha-do-Valle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00e1tia da Silva","family":"Calabrese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.actatropica.2018.06.001","article-title":"Successful treatment against American cutaneous leishmaniasis by intralesional infiltration of a generic antimonial compound-lidocaine combination. 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