학술논문
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
Document Type
article
Author
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
Source
Frontiers in Cellular and Infection Microbiology, Vol 13 (2023)
Subject
Language
English
ISSN
2235-2988
Abstract
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