Abstract
The palladacycle complex DPPE 1.2 was previously shown to inhibit Leishmania (Leishmania) amazonensis infection in vitro and in vivo. The present study aimed to evaluate the effect of DPPE 1.2 associated with a recombinant cysteine proteinase, rLdccys1, and the adjuvant Propionibacterium acnes on L. (L.) amazonensis infection in two mouse strains, BALB/c, and C57BL/6. Treatment with this association potentiated the leishmanicidal effect of DPPE 1.2 resulting in a reduction of parasite load in both strains of mice which was higher compared to that found in groups treated with either DPPE 1.2 alone or associated with P. acnes or rLdccys1. The reduction of parasite load in both mice strains was followed by immunomodulation mediated by an increase of memory CD4+ and CD8+ T lymphocytes, IFN-γ levels and reduction of active TGF-β in treated animals. No infection relapse was observed 1 month after the end of treatment in mice which received DPPE 1.2 associated with rLdccys1 or rLdccys1 plus P. acnes in comparison to that exhibited by animals treated with DPPE 1.2 alone. Evaluation of serum levels of AST, ALT, urea, and creatinine showed no alterations among treated groups, indicating that this treatment schedule did not induce hepato or nephrotoxicity. These data indicate the potential use of this association as a therapeutic alternative for cutaneous leishmaniasis caused by L. (L) amazonensis.
Highlights
Leishmaniasis comprise a group of vector-borne diseases caused by protozoans of Leishmania genus and represent an important public health problem with a broad clinical spectrum and epidemiological diversity
The treatment with DPPE 1.2 associated with rLdccys1 plus P. acnes, hereafter referred as triple association, was performed by administration of 3.36 mg/Kg of DPPE 1.2, 150 mg/animal of rLdccys1 and 300 mg/animal of P. acnes
There were no significant differences between the parasite load of animals treated with either phosphate-buffered saline (PBS) or P. acnes
Summary
Leishmaniasis comprise a group of vector-borne diseases caused by protozoans of Leishmania genus and represent an important public health problem with a broad clinical spectrum and epidemiological diversity. Miltefosine, initially developed as an antitumor drug, was effective for the treatment of cutaneous and visceral leishmaniasis, representing a promising candidate due to its oral administration, but its use is limited by problems such as teratogenicity and parasite resistance [5,6,7]. It is imperative the development of new therapeutic alternatives for control of leishmaniasis and among them, the development of natural and synthetic products, molecular modifications of existing compounds and drug repositioning have shown different degrees of efficacy in the treatment of experimental leishmaniasis. Recent findings identified immunomodulators able to increase the efficacy of leishmanicidal compounds [12, 13]
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