Treatment with synthetic lipophilic tyrosyl ester controls Leishmania major infection by reducing parasite load in BALB/c mice

Treatment with synthetic lipophilic tyrosyl ester controls Leishmania major infection by reducing parasite load in BALB/c mice

Synthesized lipophilic tyrosyl ester derivatives with increasing lipophilicity were effective against Leishmania (L.) major and Leishmania infantum species in vitro. These findings prompted us to test in vivo leishmanicidal properties of these molecules and their potential effect on the modulation o...

Full description

Saved in:
Bibliographic Details
Published in:Parasitology Vol. 143; no. 12; p. 1615
Main Authors: Sghaier, Rabiaa M, Aissa, Imen, Attia, Hanène, Bali, Aymen, Leon Martinez, Pablo A, Mkannez, Ghada, Guerfali, Fatma Z, Gargouri, Youssef, Laouini, Dhafer
Format: Journal Article
Language:English
Published: England 01-10-2016
Subjects:
Animals
Antiprotozoal Agents - administration & dosage
Cytokines - secretion
Disease Models, Animal
Immunologic Factors - administration & dosage
Injections, Subcutaneous
Leishmania major - drug effects
Leishmaniasis, Cutaneous - drug therapy
Mice
Mice, Inbred BALB C
Parasite Load
Th1 Cells - immunology
Tyrosine - analogs & derivatives
Tyrosine - pharmacology
anti-leishmanial activity
lipophilic tyrosyl ester
parasite load
Leishmania major
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Synthesized lipophilic tyrosyl ester derivatives with increasing lipophilicity were effective against Leishmania (L.) major and Leishmania infantum species in vitro. These findings prompted us to test in vivo leishmanicidal properties of these molecules and their potential effect on the modulation of immune responses. The experimental BALB/c model of cutaneous leishmaniasis was used in this study. Mice were infected with L. major parasites and treated with three in vitro active tyrosyl esters derivatives. Among these tested tyrosylcaprate (TyC) compounds, only TyC10 exhibited an in vivo anti-leishmanial activity, when injected sub-cutaneously (s.c.). TyC10 treatment of L. major-infected BALB/c mice resulted in a decrease of lesion development and parasite load. TyC10 s.c. treatment of non-infected mice induced an imbalance in interferon γ/interleukin 4 (IFN-γ/IL-4) ratio cytokines towards a Th1 response. Our results indicate that TyC10 s.c. treatment improves lesions' healing and parasite clearance and may act on the cytokine balance towards a Th1 protective response by decreasing IL-4 and increasing IFN-γ transcripts. TyC10 is worthy of further investigation to uncover its mechanism of action that could lead to consider this molecule as a potential drug candidate.
ISSN:1469-8161
DOI:10.1017/S0031182016001086