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:	Meira RMV; Laboratório de Imunofarmacologia Parasitária, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil., Gomes SLDS; Laboratório de Catálise Orgânica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Schaeffer E; Laboratório de Catálise Orgânica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Da Silva T; Laboratório de Imunofarmacologia Parasitária, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil., Brito ACS; Laboratório de Imunofarmacologia Parasitária, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil., Siqueira LM; Laboratório de Imunofarmacologia Parasitária, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil., Inácio JD; Laboratório de Bioquímica de Tripanosomatídeos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Almeida-Amaral EE; Laboratório de Bioquímica de Tripanosomatídeos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Da-Cruz AM; Disciplina de Parasitologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.; Laboratório Interdisciplinar de Pesquisas Médicas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Bezerra-Paiva M; Laboratório Interdisciplinar de Pesquisas Médicas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Neves RH; Laboratório de Helmintologia Romero Lascasas Porto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil., Rodrigues LS; Laboratório de Imunopatologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil., Dutra PML; Laboratório de Imunologia do Exercício, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil., Costa PRR; Laboratório de Química Bioorgânica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., da Silva AJM; Laboratório de Catálise Orgânica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Da-Silva SAG; Laboratório de Imunofarmacologia Parasitária, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2023 Jan 19; Vol. 13, pp. 1025359. Date of Electronic Publication: 2023 Jan 19 (Print Publication: 2023).
DOI:	10.3389/fcimb.2023.1025359
Abstrakt:	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 (CC 50 >3200 µM/48h) and activity against intracellular amastigotes (IC 50 = 193 ± 19 µM/48h) and promastigotes (IC 50 = 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<0.001) in the lesion. The reduction of parasite load by 3-PL treatment was comparable to reference drug meglumine antimoniate administered by the same routes (subcutaneous 1mg/Kg and tattoo 0.1mg/Kg). In addition, treatment started from five weeks after infection with 3-PL per tattoo also decreased the parasite load. These results show the anti-leishmanial effect of 3-PL against L. ( V. ) braziliensis and its efficacy by subcutaneous (higher dose) and tattoo (lower dose) routes. In addition, this study shows that drug delivery by tattooing the lesion allows the use of lower doses than the conventional subcutaneous route, which may support the development of a new therapeutic strategy that can be adopted for leishmaniasis. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Meira, Gomes, Schaeffer, Da Silva, Brito, Siqueira, Inácio, Almeida-Amaral, Da-Cruz, Bezerra-Paiva, Neves, Rodrigues, Dutra, Costa, da Silva and Da-Silva.)
Databáze:	MEDLINE
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