In vitro activity of phospholipase A2 and of peptides from Crotalus durissus terrificus venom against amastigote and promastigote forms of Leishmania (L.) infantum chagasi

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BackgroundApis mellifera venom, which has already been recommended as an alternative anti-inflammatory treatment, may be also considered an important source of candidate molecules for biotechnological and biomedical uses, such as the treatment of parasitic diseases.MethodsAfricanized honeybee venom from Apis mellifera was fractionated by RP-C18-HPLC and the obtained melittin was incubated with promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Cytotoxicity to mice peritoneal macrophages was evaluated through mitochondrial oxidative activity. The production of anti- and pro-inflammatory cytokines, NO and H2O2 by macrophages was determined.ResultsPromastigotes and intracellular amastigotes were susceptible to melittin (IC50 28.3 μg.mL−1 and 1.4 μg.mL−1, respectively), but also showed mammalian cell cytotoxicity with an IC50 value of 5.7 μg.mL−1. Uninfected macrophages treated with melittin increased the production of IL-10, TNF-α, NO and H2O2. Infected melittin-treated macrophages increased IL-12 production, but decreased the levels of IL-10, TNF-α, NO and H2O2.ConclusionsThe results showed that melittin acts in vitro against promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Furthermore, they can act indirectly on intracellular amastigotes through a macrophage immunomodulatory effect.

Section: Discussionmentioning

confidence: 99%

Melittin induces in vitro death of Leishmania (Leishmania) infantum by triggering the cellular innate immune response

Pereira¹,

Barros²,

Pinto³

et al. 2016

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“…Phospholipases A 2 (PLA 2 ) (EC 3.1.1.4) were the first phospholipases to be known and their discovery was based on observation of the action of pancreatic fluid of mammals and snake venom in the hydrolysis of phosphatidylcholine [9]. …”

Section: Phospholipases A2 (Pla2)mentioning

confidence: 99%

Alpha-type phospholipase A2 inhibitors from snake blood

Santos-Filho

Santos

2017

It is of popular and scientific knowledge that toxins from snake venom (among them the PLA2 and myotoxins) are neutralized by various compounds, such as antibodies and proteins purified from animal blood. Venomous and nonvenomous snakes have PLA2 inhibitory proteins, called PLIs, in their blood serum. One hypothesis that could explain the presence of these PLIs in the serum of venomous snakes would be self-protection against the enzymes of their own venom, which eventually could reach the circulatory system. However, the presence of PLIs in non-venomous snakes suggests that their physiological role might not be restricted to protection against PLA2 toxins, but could be extended to other functions, as in the innate immune system and local regulation of PLA2s. The present study aimed to review the currently available literature on PLA2 and myotoxin alpha inhibitors present in snake plasma, thus helping to improve the research on these molecules. Furthermore, this review includes current information regarding the mechanism of action of these inhibitors in an attempt to better understand their application, and proposes the use of these molecules as new models in snakebite therapy. These molecules may help in the neutralization of different types of phospholipases A2 and myotoxins, complementing the conventional serum therapy.

“…These results agree with a previous work that suggested that venom toxins specifically targets cancer cells without affecting normal ones [ 23 ]. It indicates a difference of cell membranes between cancer and normal cells, which reveals the variation of phospholipid domains in different cell types [ 14 , 18 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Anticancer properties of phospholipase A2 from Daboia siamensis venom on human skin melanoma cells

Khunsap

Khow

Buranapraditkun

et al. 2016

BackgroundPhospholipase A2 (PLA2) is a major component of the Daboia siamensis venom, which is able to hydrolyse the membrane of various cells. For this reason, the activity of PLA2 was investigated regarding its pharmaceutical properties. This study was conducted to explore the pharmacological properties of a PLA2 from Daboia siamensis (dssPLA2) venom on human skin melanoma cell line (SK-MEL-28).MethodsdssPLA2 was isolated by ion exchange and gel filtration columns. Various concentrations of dssPLA2 were investigated for cytotoxic activity and inhibition of migration on SK-MEL-28 cells. Cell death analysis, mRNA expression levels of Notch I-III and BRAF V600E genes were also determined.ResultsdssPLA2 exhibited cytotoxicity on SK-MEL-28 for 24 and 72 h as compared with untreated cells. However, it had no toxic effects on CCD-1064sk cells under the same conditions. dssPLA2 (0.25 and 0.5 μg/mL) induced 17.16 and 30.60 % of apoptosis, while activated 6.53 and 7.05 % of necrotic cells. dssPLA2 at 0.25, 0.5, 1 and 2 μg/mL could inhibit migration on SK-MEL-28 cells for 24 h by 31.06, 41.66, 50 and 68.75 %, respectively. The action of dssPLA2 significantly reduced the levels of Notch I and BRAF V600E genes expression on SK-MEL-28 cells compared with untreated cells at 72 h.ConclusionsThis study indicates that dssPLA2 had potential effects of apoptosis, necrosis, cytotoxicity and inhibition of migration on SK-MEL-28 cells. dssPLA2 could possibly be a selective agent that targets cancer cells without affecting normal cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s40409-016-0061-z) contains supplementary material, which is available to authorized users.