Low doses of 3-phenyl-lawsone or meglumine antimoniate delivery by tattooing route are successful in reducing parasite load in cutaneous lesions of Leishmania (Viannia) braziliensis-infected hamsters

Autor: Rafaella de Miranda Villarim Meira, Sara Lins da Silva Gomes, Edgar Schaeffer, Thayssa Da Silva, Andréia Carolinne de Souza Brito, Larissa Moreira Siqueira, Job Domingos Inácio, Elmo Eduardo Almeida-Amaral, Alda Maria Da-Cruz, Milla Bezerra-Paiva, Renata Heisler Neves, Luciana Silva Rodrigues, Patricia Maria Lourenço Dutra, Paulo Roberto Ribeiro Costa, Alcides José Monteiro da Silva, Silvia Amaral Gonçalves Da-Silva
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Cellular and Infection Microbiology, Vol 13 (2023)
Druh dokumentu: article
ISSN: 2235-2988
DOI: 10.3389/fcimb.2023.1025359
Popis: Current therapeutic ways adopted for the treatment of leishmaniasis are toxic and expensive including parasite resistance is a growing problem. Given this scenario, it is urgent to explore treatment alternatives for leishmaniasis. The aim of this study was to evaluate the effect of 3-phenyl-lawsone (3-PL) naphthoquinone on Leishmania (Viannia) braziliensis infection, both in vitro and in vivo, using two local routes of administration: subcutaneous (higher dose) and tattoo (lower dose). In vitro 3-PL showed low toxicity for macrophages (CC50 >3200 µM/48h) and activity against intracellular amastigotes (IC50 = 193 ± 19 µM/48h) and promastigotes (IC50 = 116 ± 26 µM/72h), in which induced increased ROS generation. Additionally, 3-PL up-regulated the production of cytokines such as tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-10 in infected macrophages. However, the anti-amastigote action was independent of nitric oxide production. Treatment of hamsters infected with L. (V.) braziliensis from one week after infection with 3-PL by subcutaneous (25 µg/Kg) or tattooing (2.5 µg/Kg) route, during 3 weeks (3 times/week) or 2 weeks (2 times/week) significantly decreased the parasite load (p
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