Abstract
The fact that drugs currently used in the treatment of Leishmania are highly toxic and associated with acquired resistance has promoted the search for new therapies for treating American tegumentary leishmaniasis (ATL). In this study, BALB/c mice were injected in the hind paw with Leishmania (Leishmania) amazonensis and subsequently treated with a combination of nitric oxide (NO) donor (cis-[Ru(bpy) 2imN(NO)](PF6)3) (Ru-NO), given by intraperitoneal injection, and oral Brazilian propolis for 30 days. Ru-NO reached the center of the lesion and increased the NO level in the injured hind paw without lesion exacerbation. Histological and immunological parameters of chronic inflammation showed that this combined treatment increased the efficacy of macrophages, determined by the decrease in the number of parasitized cells, leading to reduced expression of proinflammatory and tissue damage markers. In addition, these drugs in combination fostered wound healing, enhanced the number of fibroblasts, pro-healing cytokines and induced collagen synthesis at the lesion site. Overall, our findings suggest that the combination of the NO donor Ru-NO and Brazilian propolis alleviates experimental ATL lesions, highlighting a new therapeutic option that can be considered for further in vivo investigations as a candidate for the treatment of cutaneous leishmaniasis.
Highlights
Leishmania (Leishmania) amazonensis is an obligatory intracellular parasite of mammalian cells and one of the causative agents of American tegumentary leishmaniasis (ATL)
Since we demonstrated that the drug reached the lesion, we wondered if nitric oxide (NO) was released at the site of injury, employing a high-sensitivity chemiluminescence method based on the detection of NO/nitrosative stress [38]
The inflammatory response developed during Leishmaniasis is essential for controlling the parasite burden, and the clinical outcome of ATL is a result of the immune capacity of the host in building an effective adaptive response against the parasite
Summary
Leishmania (Leishmania) amazonensis is an obligatory intracellular parasite of mammalian cells and one of the causative agents of American tegumentary leishmaniasis (ATL). Infection occurs from the bite of an infected phlebotomine sand fly, and depending on the host immune response, various clinical manifestations may result, ranging from a single granulomatous skin lesion at the site of the bite to diffuse lesions, where it may or may not affect the mucous membranes or even progress to visceral disease [1]. Host susceptibility is ascribed to Th2 immune response, which leads to the development and multiplication of the parasite [4]. Among the microbicidal mechanisms exhibited by phagocytic cells, NO production has been shown to be one of the most important for eliminating Leishmania spp.[7, 8]
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