The histopathological and immunological pattern of CBA mice infected with Leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives

Abstract

Because there is no vaccine in clinical use, control of Leishmaniasis relies almost exclusively on chemotherapy and the conventional treatments exhibit high toxicity for patients and emerging drug resistance. Recently, we showed that oral treatment with synthetic pyrazole carbohydrazide compounds induced lower parasite load in draining lymph nodes and reduced skin lesion size without causing any toxic effects in an experimental murine infection model with Leishmania amazonensis. In this study, CBA mice were infected in the footpad with L. amazonensis and then orally treated with pyrazole carbohydrazides derivatives, such as BrNO(2), NO(2)Cl and NO(2)Br and their histopathological and immunological effects were then investigated. Epidermis and dermis had lower levels of inflammatory infiltration compared to the infected untreated control mice. In the dermis of treated animals, the numbers of vacuolated macrophages containing intracellular parasites were far lower than in infected untreated animals. In addition to dermal macrophages, we also observed a mixed inflammatory infiltrate containing lymphocytes and granulocyte cells. Lower numbers of B cells (B220+) and T lymphocytes (CD3+) were identified in the lesions of treated mice compared with the untreated, infected mice. In draining lymph node cells, the number of T lymphocytes (CD3+) was decreased, and the numbers of B cells (CD19+) and CD8+ T cells were increased in infected mice, when compared with the non-infected control group. In additional, we have shown that infected treated and untreated lymph node cells had similar levels of TGF-β and IFN-γ mRNA expression, whereas IL-4 was expressed at a lower level in the treated group. Increased levels of the specific anti-Leishmania IgG2a or IgG3 antibody subclass were observed in NO(2)Cl or BrNO(2)-treated group, respectively. Overall, our experimental findings suggest that pyrazole carbohydrazides exert modulation of IL-4 expression and B cell levels; however, further evaluation is required to determine the optimal treatment regime.

A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis

“…tropica –CsS-16 [ 48 ], L . amazonensis –CBA [ 18 ], and L . braziliensis –golden hamster [ 66 ], which each show promise for drug discovery ( Table 1 ).…”

“…Nonhuman primate models are often used for the evaluation of potential anti-leishmanial compounds as a precursor to human clinical trials [ 17 ]. However, the results achieved from these nonhuman primate studies are often no better than those from the rodent models, and their use over rodent models may even be inferior [ 18 ]. The determination of parasite load within the animal model is also an important factor to consider when establishing the efficacy of a compound.…”

“…In the study by Charret et al, 2013, the CBA strain was chosen over the BALB/c strain due to its susceptibility to infection by L . amazonensis , developing cutaneous lesions without intense parasite dissemination [ 18 ]. It was also noted from Lemos de Souza, et al, 2000, that CBA mice infected with L .…”

Diffuse Reflectance Parameters of Treated Leishmaniasis Cutaneous Ulcers and Association with Histopathologies in an Animal Model: A Proof of Concept

“…For example, in CBA mice infected in the skin of the footpad of an upper limb with L. amazonensis , a mixture of inflammatory cells, including macrophages, lymphocytes, neutrophils, and eosinophils, were observed as infiltrating cells. 62…”

VULGARIS ACTIVITY AGAINST OF Leishmania tropica PROMASTIGOTES; IN VITRO.

“…Considering the inefficiency of current drugs and the fact that some varieties of Leishmania are resistant to these treatments, new drugs are being researched in order to find a more selective and effective therapy with fewer side effects. Therefore, our research group conducted studies on new therapeutic agents (Charret et al, 2009;Charret et al, 2013;Marra et al, 2012). The literature has reported several studies about biological activities of extracts from marine algae (Shalaby, 2011).…”