Abstract
Leishmaniasis is an infectious disease caused by protozoans of the genus Leishmania. The macrophage is the resident cell in which the parasite replicates and it is important to identify new compounds that can aid in parasite elimination since the drugs used to treat leishmaniasis are toxic and present side effects. We have previously shown that treatment of Leishmania braziliensis-infected macrophages with DETC (Diethyldithiocarbamate) induces parasite killing, in vivo. Thus, the objective of this study was to further evaluate the effect of oxidants and antioxidants in L. braziliensis-infected macrophages, following treatment with either oxidizing Hydrogen Peroxide, Menadione, DETC, or antioxidant [NAC (N-Acetyl-Cyteine), Apocynin, and Tempol] compounds. We determined the percentage of infected macrophages and number of amastigotes. Promastigote survival was also evaluated. Both DETC (SOD-inhibitor) and Tempol (SOD-mimetic) decreased the percentage of infected cells and parasite load. Hydrogen peroxide did not interfere with parasite burden, while superoxide-generator Menadione had a reducing effect. On the other hand, NAC (GSH-replenisher) and Apocynin (NADPH-oxidase inhibitor) increased parasite burden. Tempol surfaces as an interesting candidate for the chemotherapy of CL with an IC50 of 0.66 ± 0.08 mM and selectivity index of 151. While it remains obscure how a SOD-mimetic may induce leishmanicidal effects, we suggest the possibility of developing Tempol-based topical applications for the treatment of cutaneous leishmaniasis caused by L. braziliensis.
Highlights
Leishmaniasis is zoonotic infection widely distributed from Asia to America which exhibits a high mortality rate
We have previously shown that DETC can be used as a topical treatment in the cutaneous lesions caused by L. braziliensis (Celes et al, 2016), suggesting that manipulation of the redox status during in vitro infection with L. braziliensis can contribute to the identification of novel therapeutic alternatives
We tested a number of compounds for their ability to modulate the oxidative stress in macrophages infected with L. braziliensis
Summary
Leishmaniasis is zoonotic infection widely distributed from Asia to America which exhibits a high mortality rate. The clinical forms of leishmaniasis depend on the infecting organism and the general state of the host’s immune response and are divided in visceral leishmaniasis (VL) and tegumentary leishmaniasis (TL). TL is characterized by cutaneous or mucosal lesions with low lethality, but with high morbidity. CL caused by Leishmania braziliensis is distinguished from other leishmaniasis by its chronicity, latency, and tendency to metastasize in the human host (Bittencourt et al, 2003). Brazil along with nine other countries account for 70–75% of the global CL incidence (Alvar et al, 2012). First choice drugs for leishmaniasis chemotherapy are pentavalent antimonials (Sbv)
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