Article
The histopathological and immunological pattern of CBA mice infected with Leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives
Registro en:
CHARRET, Karen S.; et al. The histopathological and immunological pattern of CBA mice infected with Leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives. Experimental Parasitology, v.133, n.2, p.201–210, 2013.
0014-4894
10.1016/j.exppara.2012.11.022
Autor
Charret, Karen S.
Cândido, Jussara Lagrota
Pinto, Carla E. Carvalho
Hottz, Cristiane F.
Lira, Marie Luce F.
Rodrigues, Raquel F.
Gomes, Adriana O.
Bernardino, Alice M.
Cavalheiro, Marilene M. Canto
Leon, Leonor L.
Amaral, Veronica F.
Resumen
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 BrNO2, NO2Cl and NO2Br 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-b and
IFN-c 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 NO2Cl or BrNO2-
treated group, respectively. Overall, our experimental findings suggest that pyrazole carbohydrazides.