PMID- 36743305
OWN - NLM
STAT- MEDLINE
DCOM- 20230207
LR  - 20230306
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 13
DP  - 2023
TI  - 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.
PG  - 1025359
LID - 10.3389/fcimb.2023.1025359 [doi]
LID - 1025359
AB  - 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 microM/48h) and activity against intracellular amastigotes (IC(50) = 193 +/- 19 
      microM/48h) and promastigotes (IC(50) = 116 +/- 26 microM/72h), in which induced increased 
      ROS generation. Additionally, 3-PL up-regulated the production of cytokines such 
      as tumor necrosis factor alpha (TNF-alpha), 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 microg/Kg) or tattooing (2.5 microg/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.
CI  - Copyright (c) 2023 Meira, Gomes, Schaeffer, Da Silva, Brito, Siqueira, Inacio, 
      Almeida-Amaral, Da-Cruz, Bezerra-Paiva, Neves, Rodrigues, Dutra, Costa, da Silva 
      and Da-Silva.
FAU - Meira, Rafaella de Miranda Villarim
AU  - Meira RMV
AD  - Laboratorio de Imunofarmacologia Parasitaria, Universidade do Estado do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Gomes, Sara Lins da Silva
AU  - Gomes SLDS
AD  - Laboratorio de Catalise Organica, Universidade Federal do Rio de Janeiro, Rio de 
      Janeiro, Brazil.
FAU - Schaeffer, Edgar
AU  - Schaeffer E
AD  - Laboratorio de Catalise Organica, Universidade Federal do Rio de Janeiro, Rio de 
      Janeiro, Brazil.
FAU - Da Silva, Thayssa
AU  - Da Silva T
AD  - Laboratorio de Imunofarmacologia Parasitaria, Universidade do Estado do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Brito, Andreia Carolinne de Souza
AU  - Brito ACS
AD  - Laboratorio de Imunofarmacologia Parasitaria, Universidade do Estado do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Siqueira, Larissa Moreira
AU  - Siqueira LM
AD  - Laboratorio de Imunofarmacologia Parasitaria, Universidade do Estado do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Inacio, Job Domingos
AU  - Inacio JD
AD  - Laboratorio de Bioquimica de Tripanosomatideos, Fundacao Oswaldo Cruz, Rio de 
      Janeiro, Brazil.
FAU - Almeida-Amaral, Elmo Eduardo
AU  - Almeida-Amaral EE
AD  - Laboratorio de Bioquimica de Tripanosomatideos, Fundacao Oswaldo Cruz, Rio de 
      Janeiro, Brazil.
FAU - Da-Cruz, Alda Maria
AU  - Da-Cruz AM
AD  - Disciplina de Parasitologia, Universidade do Estado do Rio de Janeiro, Rio de 
      Janeiro, Brazil.
AD  - Laboratorio Interdisciplinar de Pesquisas Medicas, Fundacao Oswaldo Cruz, Rio de 
      Janeiro, Brazil.
FAU - Bezerra-Paiva, Milla
AU  - Bezerra-Paiva M
AD  - Laboratorio Interdisciplinar de Pesquisas Medicas, Fundacao Oswaldo Cruz, Rio de 
      Janeiro, Brazil.
FAU - Neves, Renata Heisler
AU  - Neves RH
AD  - Laboratorio de Helmintologia Romero Lascasas Porto, Universidade do Estado do Rio 
      de Janeiro, Rio de Janeiro, Brazil.
FAU - Rodrigues, Luciana Silva
AU  - Rodrigues LS
AD  - Laboratorio de Imunopatologia, Faculdade de Ciencias Medicas, Universidade do 
      Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Dutra, Patricia Maria Lourenco
AU  - Dutra PML
AD  - Laboratorio de Imunologia do Exercicio, Universidade do Estado do Rio de Janeiro, 
      Rio de Janeiro, Brazil.
FAU - Costa, Paulo Roberto Ribeiro
AU  - Costa PRR
AD  - Laboratorio de Quimica Bioorganica, Universidade Federal do Rio de Janeiro, Rio 
      de Janeiro, Brazil.
FAU - da Silva, Alcides Jose Monteiro
AU  - da Silva AJM
AD  - Laboratorio de Catalise Organica, Universidade Federal do Rio de Janeiro, Rio de 
      Janeiro, Brazil.
FAU - Da-Silva, Silvia Amaral Goncalves
AU  - Da-Silva SAG
AD  - Laboratorio de Imunofarmacologia Parasitaria, Universidade do Estado do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230119
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - 75G4TW236W (Meglumine Antimoniate)
RN  - TLH4A6LV1W (lawsone)
RN  - 0 (Antiprotozoal Agents)
RN  - 0 (Naphthoquinones)
SB  - IM
MH  - Cricetinae
MH  - Animals
MH  - Meglumine Antimoniate/pharmacology/therapeutic use
MH  - *Leishmania braziliensis
MH  - *Tattooing
MH  - *Antiprotozoal Agents/pharmacology/therapeutic use
MH  - *Leishmaniasis, Cutaneous/drug therapy/parasitology
MH  - *Naphthoquinones/pharmacology/therapeutic use
MH  - Parasite Load
PMC - PMC9892647
OTO - NOTNLM
OT  - 3-phenyl-lawsone
OT  - Leishmania (Viannia) braziliensis
OT  - chemotherapy
OT  - hamster-model
OT  - subcutaneous
OT  - tattooing
COIS- 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.
EDAT- 2023/02/07 06:00
MHDA- 2023/02/08 06:00
PMCR- 2023/01/01
CRDT- 2023/02/06 03:52
PHST- 2022/08/22 00:00 [received]
PHST- 2023/01/02 00:00 [accepted]
PHST- 2023/02/06 03:52 [entrez]
PHST- 2023/02/07 06:00 [pubmed]
PHST- 2023/02/08 06:00 [medline]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fcimb.2023.1025359 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2023 Jan 19;13:1025359. doi: 
      10.3389/fcimb.2023.1025359. eCollection 2023.