Acid heteropolysaccharides with potent antileishmanial effects

Kangussu-Marcolino, Mônica Mendes; Rosário, Marianna Maia Taulois do; Noseda, Miguel D.; Duarte, Maria Eugênia R.; Ducatti, Diogo R.B.; Cassolato, Juliana Emanuela Fogari; Iacomini, Marcello; Martinez, Gláucia Regina; Rocha, Maria Eliane Merlin; Cadena, Sílvia Maria Suter Correia; Noleto, Guilhermina Rodrigues

doi:10.1016/j.ijbiomac.2015.07.006

Cited by 7 publications

(3 citation statements)

References 46 publications

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“…Among these are ones derived from arabinogalactan and isolated from Anadenanthera colubrina , which induces increased nitric oxide by macrophages. 79 Alkaloids derived from Aspidosperma ramiflorum have shown activity against promastigotes. 80 Also, alkaloids derived from marine sources exhibit excellent in vitro antileishmanial activity, inhibiting DNA synthesis.…”

Section: Treatment Of Vl–hiv Coinfectionmentioning

confidence: 99%

Visceral leishmaniasis and HIV coinfection: current perspectives

Lindoso¹,

Moreira²,

Cunha³

et al. 2018

HIV

112

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Visceral leishmaniasis (VL) is caused by Leishmania donovani and Leishmania infantum. The burden of VL is concentrated in tropical and subtropical areas; however, HIV infection has spread VL over a hyperendemic area. Several outcomes are observed as a result of VL–HIV coinfection. Impacts are observed in immunopathogenesis, clinical manifestation, diagnosis, and therapeutic response. Concerning clinical manifestation, typical and unusual manifestation has been observed during active VL in HIV-infected patient, as well as alteration in immunoresponse, inducing greater immunosuppression by low CD4 T-lymphocyte count or even by induction of immunoactivation, with cell senescence. Serological diagnosis of VL in the HIV-infected is poor, due to low humoral response, characterized by antibody production, so parasitological methods are more recommended. Another important and even more challenging point is the definition of the best therapeutic regimen for VL in HIV-coinfected patients, because in this population there is greater failure and consequently higher mortality. The challenge of better understanding immunopathogenesis in order to obtain more effective therapies is one of the crucial points to be developed. The combination of drugs and the use of secondary prophylaxis associated with highly active antiretroviral therapy may be the best tool for treatment of HIV coinfection. Some derivatives from natural sources have action against Leishmania; however, studies have been limited to in vitro evaluation, without clinical trials.

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Section: Treatment Of Vl–hiv Coinfectionmentioning

confidence: 99%

Visceral leishmaniasis and HIV coinfection: current perspectives

Lindoso¹,

Moreira²,

Cunha³

et al. 2018

HIV

112

View full text Add to dashboard Cite

show abstract

“…The parasite-macrophage interplay begins when macrophages detect parasite molecules through membrane receptors, which then stimulate the production of proinflammatory cytokines, such as TNF-α, IFN-γ, IL-12, IL-1β and of hydrogen peroxide, triggering the Th-1 type cellular response, which is related to the efficiency in the elimination of the intracellular parasites (7). However, in the amastigote form, the parasite is able to inhibit hydrolytic enzymes and deplete reactive species of nitrogen and oxygen while remaining protected and is capable of multiplying in the phagolysosome (8).…”

Section: Introductionmentioning

confidence: 99%

MARBOFLOXACIN INDUCES LEISHMANICIDAL ACTIVITY AND LESS INFLAMMATORY RESPONSE IN Leishmania chagasi INFECTED MACROPHAGES

Amante

Santos

et al. 2020

RVZ

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Marbofloxacin has promising leishmanicidal activity due to the direct action on the Leishmania chagasi amastigotes. It was developed only for veterinary medicine uses, and it could be used as an drug for the treatment of Canine Visceral Leishmaniasis (CVL). In the present study, we evaluated the leishmanicidal effect and macrophage modulation of marbofloxacin in macrophages infected with amastigotes of L. chagasi. Macrophages were collected from peritoneum of BALB/c mice and infected with promastigotes of L. chagasi. After internalization and transformation into amastigotes forms, cells were treated with marbofloxacin in concentration of 100, 500 and 750 μg/mL for 18 hours. The leishmanicidal effect was evaluated by morphological spects of amastigotes inside of macrophages by phagocytosis assay and detection of death amastigotes and macrophages by TUNEL assay. Macrophage modulation was evaluated by release of cytotoxic metabolites and cytokine production. The results showed that L. chagasi-infected macrophages treated with the highest concentration of the drug showed lower amount of amastigotes into the macrophages (p<0,0632) than untreated infected cells. There was pronounced presence of cellular vacuoles in the treated infected-cells, and more apoptotic amastigotes in alive macrophages. It was observed decreased levels of H2O2, IL-1β, IL-6, and TNF-α dose-dependent of marbofloxacin in infected macrophages. The results indicate the leishmanicidal effect of marbofloxacin in infected macrophages and immunomodulation actions in these cells.

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“…The antileishmanial effects of the polysaccharides occurred by different mechanisms: for sulfated polysaccharides, this may be an expressive increase in NO production by macrophages, while for arabinogalactan, it may be attributed to stimulation of O 2 •− and TNF production. 113 Polysaccharide polymers have also been used to deliver vanadium complexes, which are reported to be highly active metal-based drugs against a variety of trypanosomatids, including Leishmania species. 114 The immunomodulatory effects of the polysaccharides arabinogalactan, galactomannan, and xyloglucan, as well as their oxovanadium (IV/V) complexes, were evaluated on peritoneal macrophages exhibiting significant leishmanicidal activity (~60%-70%).…”

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confidence: 99%

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

Bruni¹,

Stella²,

Giraudo³

et al. 2017

IJN

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Leishmaniasis is a vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania , which are responsible for numerous clinical manifestations, such as cutaneous, visceral, and mucocutaneous leishmaniasis, depending on the site of infection for particular species. These complexities threaten 350 million people in 98 countries worldwide. Amastigotes living within macrophage phagolysosomes are the principal target of antileishmanial treatment, but these are not an easy target as drugs must overcome major structural barriers. Furthermore, limitations on current therapy are related to efficacy, toxicity, and cost, as well as the length of treatment, which can increase parasitic resistance. Nanotechnology has emerged as an attractive alternative as conventional drugs delivered by nanosized carriers have improved bioavailability and reduced toxicity, together with other characteristics that help to relieve the burden of this disease. The significance of using colloidal carriers loaded with active agents derives from the physiological uptake route of intravenous administered nanosystems (the phagocyte system). Nanosystems are thus able to promote a high drug concentration in intracellular mononuclear phagocyte system (MPS)-infected cells. Moreover, the versatility of nanometric drug delivery systems for the deliberate transport of a range of molecules plays a pivotal role in the design of therapeutic strategies against leishmaniasis. This review discusses studies on nanocarriers that have greatly contributed to improving the efficacy of antileishmaniasis drugs, presenting a critical review and some suggestions for improving drug delivery.

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Acid heteropolysaccharides with potent antileishmanial effects

Cited by 7 publications

References 46 publications

Visceral leishmaniasis and HIV coinfection: current perspectives

Visceral leishmaniasis and HIV coinfection: current perspectives

MARBOFLOXACIN INDUCES LEISHMANICIDAL ACTIVITY AND LESS INFLAMMATORY RESPONSE IN Leishmania chagasi INFECTED MACROPHAGES

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

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