Nitric oxide production by Peromyscus yucatanicus (Rodentia) infected with Leishmania (Leishmania) mexicana

Loría-Cervera, Elsy Nalleli; Sosa-Bibiano, Erika Ivett; Villanueva‐Lizama, Liliana; Wynsberghe, Nicole R. Van; Canto-Lara, Silvia B.; Batún-Cutz, José; Andrade-Narvaez, Fernando J.

doi:10.1590/0074-0276108022013008

Cited by 10 publications

(4 citation statements)

References 35 publications

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“…The α -bisabolol is a sesquiterpene with low toxicity and is used in the cosmetic industry [32, 33] where it presents a pro-apoptotic activity [34]. Its leishmanicidal action against promastigotes and intracellular amastigotes may occur directly or indirectly through the production of cellular mechanisms, such as the production of nitric oxide (NO), which is the major effector molecule that participates in the intracellular killing of Leishmania [35]. The hydrophobic nature and the toxic effects of essential oils and their major constituents against various microorganisms are a common feature of plants which have volatile oils.…”

Section: Resultsmentioning

confidence: 99%

In VitroAntileishmanial Activity of Essential Oil ofVanillosmopsis arborea(Asteraceae) Baker

Colares

Almeida-Souza

Taniwaki

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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The search for new immunopharmacological chemical agents to treat various diseases caused by bacteria, fungi, and protozoa, such as leishmaniasis, for example, has led to the exploration of potential products from plant species and their main active ingredients. Antimonial drugs are the current treatment for leishmaniasis. These drugs cause major side effects and frequent discontinuation of treatment. In this study, we evaluated the in vitro leishmanicidal activity of essential oil of Vanillosmopsis arborea (VAEO) and its major compound α-bisabolol against Leishmania amazonensis. The essential oil and α-bisabolol showed activity against promastigotes (IC50 7.35 and 4.95 μg/mL resp.) and intracellular amastigotes (IC50 12.58 and 10.70 μg/mL, resp.). Neither product showed any cytotoxicity on treated macrophages. The ultrastructural analysis of promastigotes incubated with VAEO or α-bisabolol at 30 μg/mL, showed morphological changes with the accumulation of vesicles electrodense lipid inclusions. The results give evidence that both VAEO and α-bisabolol have potential as new therapeutic agents against leishmaniasis.

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Section: Resultsmentioning

confidence: 99%

In VitroAntileishmanial Activity of Essential Oil ofVanillosmopsis arborea(Asteraceae) Baker

Colares

Almeida-Souza

Taniwaki

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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“…Moreover 100% of P. yucatanicus inoculated with 10 2 (“low inoculum”) developed subclinical infection (absence of clinical signs and evidence of parasite's DNA at the site of inocula) and when immunosupressed with cyclophosphamide a reactivation with the appearance of lesions was observed 29 . Nitric oxide production was documented in co-cultured macrophages and lymphocytes from P. yucatanicus with clinical and subclinical infection caused by L. (L.) mexicana 64 . Although NO production was observed in these wild rodents, they were unable to clear the infection, which differs with the response observed in murine models where the generation of NO is the main effector mechanism involved in the control of L. major infection.…”

Section: Wild Rodentsmentioning

confidence: 99%

Animal Models for the Study of Leishmaniasis Immunology

Loría-Cervera

Andrade-Narvaez

2014

Rev. Inst. Med. trop. S. Paulo

134

101

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Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

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“…1 f), as NO is directly involved in the killing of Leishmania parasites and therefore is a key molecule in the control of the disease. Less NO production will thus decrease the leishmanicidal action of macrophages [ 45 , 46 ]. Another factor that can be related to the differences observed in parasite load is the production of cytokines.…”

Section: Discussionmentioning

confidence: 99%

Combined therapy with adipose tissue-derived mesenchymal stromal cells and meglumine antimoniate controls lesion development and parasite load in murine cutaneous leishmaniasis caused by Leishmania amazonensis

et al. 2020

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Background Leishmaniasis is a neglected disease caused by Leishmania spp. One of its characteristics is an imbalance of host immune responses to foster parasite survival. In this setting, mesenchymal stromal cells (MSCs) may be a viable therapeutic alternative, given their well-established immunomodulatory potential. In this study, we compared the effects of therapy with bone marrow (BM)- and adipose tissue (AD)-derived MSCs in leishmaniasis caused by Leishmania amazonensis in C57BL/6 mice. After determining the most effective MSC source, we then combined these cells with meglumine antimoniate (a pentavalent antimonial commonly used for the treatment of leishmaniasis) to treat the infected mice. Methods In vitro, co-culture of AD-MSCs and BM-MSCs with Leishmania amazonensis- infected macrophages was performed to understand the influence of both MSC sources in infected cells. In vivo, infected C57BL/6 mice were treated with phosphate-buffered saline (PBS), AD-MSCs and BM-MSCs, and then meglumine antimoniate was combined with MSCs from the most effective source. Results In vitro, co-culture of Leishmania amazonensis -infected macrophages with BM-MSCs, compared to AD-MSCs, led to a higher parasite load and lower production of nitric oxide. Fibroblasts grown in conditioned medium from co-cultures with AD-MSCs promoted faster wound healing. Despite a non-significant difference in the production of vascular endothelial growth factor, we observed higher production of tumor necrosis factor-α and interleukin (IL)-10 in the co-culture with AD-MSCs. In vivo, treatment of infected mice with BM-MSCs did not lead to disease control; however, the use of AD-MSCs was associated with partial control of lesion development, without significant differences in the parasite load. AD-MSCs combined with meglumine antimoniate reduced lesion size and parasite load when compared to PBS and AD-MSC groups. At the infection site, we detected a small production of IL-10, but we were unable to detect production of either IL-4 or interferon-γ, indicating resolution of infection without effect on the percentage of regulatory T cells. Conclusion Combination treatment of cutaneous leishmaniasis with AD-MSCs and meglumine antimoniate may be a viable alternative.

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Nitric oxide production by Peromyscus yucatanicus (Rodentia) infected with Leishmania (Leishmania) mexicana

Cited by 10 publications

References 35 publications

In VitroAntileishmanial Activity of Essential Oil ofVanillosmopsis arborea(Asteraceae) Baker

In VitroAntileishmanial Activity of Essential Oil ofVanillosmopsis arborea(Asteraceae) Baker

Animal Models for the Study of Leishmaniasis Immunology

Combined therapy with adipose tissue-derived mesenchymal stromal cells and meglumine antimoniate controls lesion development and parasite load in murine cutaneous leishmaniasis caused by Leishmania amazonensis

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